Key Points español 中文 (chinese) Question
How often do oncology studies assess quality of life (QoL) throughout a patient’s disease course?
Findings
This cross-sectional analysis of 149 oncology studies published in high-impact medical and oncology journals found that most studies (69.8%) assessed QoL during the intervention, whereas only 3.4% of studies assessed QoL until the time of death.
Meaning
These findings suggest that many oncology studies only assess QoL during the intervention; future research should consider the long-term outcomes throughout the patient’s life.
Importance
Quality of life (QoL) is an important consideration in cancer medicine, especially because drugs are becoming more costly and may only result in modest gains in overall survival. However, there has been no descriptive analysis for the points at which QoL is measured in cancer trials.
Objective
To estimate the prevalence of studies that measure QoL at different points and see how many studies measure QoL for the entirety of a patient’s life.
Design, Setting, and Participants
This cross-sectional analysis includes all articles on oncology clinical trials in the 3 highest-impact oncology journals, published between July 2015 and June 2018, that reported QoL outcomes.
Main Outcomes and Measures
Data were abstracted on when QoL was assessed and the characteristics of these studies.
Results
For all 149 studies that met inclusion criteria, QoL assessment was high during treatment (104 articles [69.8%]), during follow-up (81 articles [54.4%]), and after the end of the intervention (68 articles [45.6%]). In 5 of the 149 studies (3.4%), QoL was assessed until death, including in only 1 of the 74 studies on metastatic or incurable cancers. Among these 5 studies, only 1 (20%) used a drug intervention, 1 (20%) used a behavioral intervention, and 2 (40%) used a radiation intervention; only 1 of 5 was in the metastatic setting. The number of studies that reported a positive QoL outcome (ie, QoL outcome was more favorable in the intervention group than in the control group) was between 42 of 81 articles (51.9%) and 16 of 28 articles (57.1%) for most QoL assessment points but only 1 of 5 articles (20%) for studies measuring QoL until death.
Conclusions and Relevance
This study found that most clinical trials assessed QoL during the treatment or intervention and often during a given amount of follow-up but infrequently assessed QoL on disease progression and rarely followed QoL until the end of the patient’s life. Most studies reporting QoL until the end of life reported worse QoL outcomes for the intervention group than the control group. Future research and policy recommendations should consider not just short-term QoL outcomes but QoL outcomes throughout the patient’s cancer care.
Health-related quality of life (QoL) and other patient-reported outcomes are vital to assessing patient perspective and experience. They reflect patient satisfaction and perceived benefits of an intervention that are not necessarily captured by other end points. These outcomes are commonly used in clinical trials, and regulatory and reimbursement agencies have begun to require these data as part of their evaluation process.1
Such QoL outcomes can be especially important in cancer clinical trials, where the intervention may not be designed to cure the disease but may only modestly prolong life. An analysis of 71 consecutively approved cancer drugs for solid tumors found that survival was increased by a median of 2.1 months.2 In such cases, improvement in QoL is an important consideration.
One overlooked consideration in the measurement of QoL is that even though drugs are often evaluated for their effects on overall survival across the remainder of a patient’s life, QoL may not be; QoL may only be measured during or at completion of therapy and may not be measured beyond therapy. In other words, the time span over which QoL is measured until the end of life is unknown. This is important because a drug may improve QoL in the short term, but those gains may be offset by worse QoL after therapy is complete, perhaps because of few remaining effective therapies or rapid progression of disease.
For this reason, we sought to characterize QoL measurement in randomized clinical trials (RCTs) in high-impact oncology journals. Specifically, we sought to estimate the prevalence of QoL being measured until the end of life, in addition to the duration of the study intervention or after a short follow-up.
Study Design and Search Strategy
This was a retrospective cross-sectional study that sought all RCTs that reported on QoL, including health-related QoL, in 3 high-impact oncology journals. We adhered to Strengthening the Reporting of Observational studies in EpidemiologyStrengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline. We selected articles for this analysis from the 3 highest-impact oncology journals, as per impact-factor scores on Scimago Journal and Country Rank, using the most recent years (July 2015 through June 2018) of Lancet Oncology, Journal of Clinical Oncology, and JAMA Oncology. For each of the journals, we searched for the term quality of life on the journal’s website, and we limited the search to research articles only. Selected articles needed to (1) be an RCT, (2) have performed the analysis in the originally randomized groups, (3) have evaluated QoL in the study, and (4) have reported the results of the QoL analysis in the study. We excluded research letters, because they did not provide adequate detail on methods, and we excluded studies that combined multiple RCTs. The search was performed on July 2, 2018. Because we used publicly available data, and this is not human subjects research in accordance with 45 CFR §46.102(f), we did not submit this study to an institutional review board or require informed consent procedures.
Information abstracted for each article included date of publication; cancer type; setting; whether the cancer under investigation was metastatic, advanced, and/or incurable (yes, no, or not applicable, for studies where the cancer was metastatic but the intervention was designed to test palliative care or not designed to improve duration of life); intervention type (a drug, behavioral intervention, radiation regimen, surgery, treatment algorithm, device, or procedure); whether overall survival was a primary or secondary end point or not indicated; the timing of the QoL assessment; the QoL metric or metrics; whether the QoL assessment was done during the intervention; and the results of the QoL outcome (positive, negative, or indeterminate). We also abstracted the median time to deterioration in QoL and median overall survival for studies that included participants with metastatic, advanced, or incurable cancer. In some cases, we searched for companion studies, when survival metrics were reported in a separate article, or on ClinicalTrials.gov, using the study identifier in the article. Two of a group of 3 reviewers (A.H., D.H-P., and/or J.G.) independently reviewed and abstracted data from each article. A third reviewer from this group adjudicated any discrepancies.
Based on the intervention duration and the timing of the QoL assessments, we abstracted data for 5 different QoL assessment points: during the intervention, at the end of treatment, after some follow-up time after completion of the intervention, until progression of cancer, and until death. In determining whether QoL was assessed at each point, we looked at the timing of reported QoL outcomes and not at the reportedly collected QoL data. Result outcomes were considered positive when the QoL results demonstrated a beneficial outcome or if there was no decline in QoL in the presence of improved disease progression or survival (primary outcome). Results were indeterminate when there were both improvements and declines in different QoL measures. Assessment until progression was affirmative if QoL was measured at the progression of disease or the discontinuation of treatment because of progression. Assessment of QoL until death was recorded as affirmative if either the study specifically stated that QoL was measured until death or until overall survival of the study cohort was less than 50%. Because of the small number of studies reporting on some of the intervention types, some categories were collapsed (eg, treatment algorithms, devices, and procedures were combined into a category called other and surgery, radiation, and chemoradiation were combined into a chemotherapy combination category).
Because we were specifically interested in determining whether QoL was reported until death, we wanted to compare median observation time with median overall survival. As a metric for median observation time, we used median time to deterioration. We then calculated median times to deterioration by QoL outcomes. For studies that did not report median time to deterioration and stopped reporting QoL data after progression or recurrence, we used median progression-free survival or median recurrence-free survival as a surrogate for median observation time. For studies that reported QoL on all participants and had set points (eg, 6 and 18 months) for assessing QoL instead of a set frequency, we used the latest period for which there were QoL results reported. For studies reporting QoL by weeks, we converted this value to months by dividing by 4, and when days were reported, we divided by 30, so all values would have the same unit.
Frequencies were calculated for categorical variables throughout. A χ2 test of independence was used to assess differences in study qualities between those that included metastatic or incurable cancers and those that did not. We also used χ2 tests to determine global differences in whether or not QoL was assessed (during treatment, at the end of treatment, after follow-up, until disease progression, or until death) for different intervention types and QoL outcomes. The Fisher exact test was used for comparisons where there were fewer than 5 counted items in a category. These methods were also used to determine differences, if any, in the proportion of positive outcomes between the different QoL-assessment periods (all studies and metastatic or incurable cancers only). The statistical analyses were done using R version 3.5.0 (R Project for Statistical Computing) and a 2-tailed P value less than .05 as the level of significance.
There were 856 articles reviewed for inclusion, of which 149 met inclusion criteria.3-151 Studies that were excluded were not RCTs or did not analyze data in randomized groups (544 articles), did not report or assess QoL (123 articles), reported QoL in a separate manuscript (38 articles), was a research letter (1 article), or was a study that combined 3 RCTs (1 article). Seventy-four studies included people with metastatic, advanced, and/or incurable cancers (49.7%); 42 studies included patients with cancers that were not metastatic, advanced, or incurable (28.2%); and 33 studies included interventions that were not designed to improve survival (22.1%). (All references are in the eAppendix in the Supplement.)
Among eligible studies of metastatic, advanced, or incurable cancers (Table 1), 40 studies were published in Lancet Oncology, 31 studies in the Journal of Clinical Oncology, and 3 studies in JAMA Oncology. Quality of life was the primary study outcome in 2 studies (4.1%), whereas most studies did not have QoL as a primary end point (72 articles [95.9%]). Most studies used a drug intervention (68 articles [90.7%]). Forty-four studies (60.0%) reported a positive QoL outcome, 24 studies (32.0%) had negative outcomes, and 6 studies (8.0%) had indeterminate findings (eAppendix in the Supplement).
Among eligible studies with cancers that were not advanced, metastatic, or incurable and studies that used an intervention not designed to improve survival (Table 1), 25 were published in Lancet Oncology,42 in the Journal of Clinical Oncology, and 8 in JAMA Oncology. Quality of life was the primary study outcome in 10.8% (9 studies), whereas most studies did not have QoL as a primary end point (66 articles [89.2%]). Most studies used a drug intervention (33 articles [44.6%]), 21 studies used a behavioral intervention (27.0%), 9 studies used therapeutic radiation as an intervention (12.2%), 1 study concerned a surgery intervention (1.4%), 8 studies used a chemotherapy regimen (with or without surgery, radiation, or another drug [10.8%]), and 3 studies had some other type of intervention (a device, treatment algorithm, or procedure [4.1%]). The most common QoL outcome was positive (40 articles [52.7%]); 31 studies (41.9%) had negative outcomes, and 4 (5.4%) had indeterminate outcomes (eAppendix in the Supplement).
For all studies and interventions, QoL assessment was high during the intervention (66 articles [89.2%] on metastatic cancers; 38 articles [50.7%] on nonmetastatic cancers), after the end of the intervention (33 articles [44.6%] on metastatic cancers; 35 articles [46.7%] on nonmetastatic cancers), and during follow-up (32 articles [43.2%] on metastatic cancers; 49 articles [65.3%] on nonmetastatic cancers) (Table 1). The assessment of QoL until the time of death was low for studies of both metastatic cancers (1 article [1.4%]) and nonmetastatic cancers (4 articles [5.3%]) (eAppendix in the Supplement).
For studies that measured QoL during treatment, 87 studies (83.7%) used a drug intervention and 8 studies (7.7%) used a behavioral intervention (Table 2). For studies that measured QoL until the end of treatment, 50 studies (73.5%) used a drug intervention and 11 studies (16.2%) used a behavioral intervention. For studies that measured QoL after some amount of follow-up time, 46 studies (56%) used a drug intervention and 14 studies (17.3%) used a behavioral intervention. For studies measuring QoL on progression, 25 studies (89.3%) used a drug intervention and none used a behavioral intervention. For studies that measured QoL until death, only 1 study (20%) used a drug intervention, 1 study (20%) used a behavioral intervention, and 2 studies (40%) used a radiation intervention (eAppendix in the Supplement).
The number of studies that reported a positive QoL outcome was 59 (56.7%) for studies that measured QoL during treatment (Table 3), 35 (51.5%) for studies that measured QoL at the end of treatment, 42 (51.9%) for studies measuring QoL after some amount of follow-up time, 16 (57.1%) for studies measuring QoL on progression, and 1 (20%) for studies measuring QoL until death (eAppendix in the Supplement). Similar patterns in the distribution of positive QoL outcomes were seen for studies that included metastatic, advanced, or incurable cancers. Figure 1 (for studies in which the median overall survival was reached) and Figure 2 (for studies in which the median overall survival was not reached) show the comparison of overall survival and the duration that QoL was assessed in studies that included patients with metastatic, advanced, or incurable cancers.
In a systematic sampling of QoL studies in high-impact oncology journals, we found that most studies assessed QoL during the treatment or intervention and often during a given amount of follow-up but often did not assess QoL on progression and rarely assessed QoL until the end of the patient’s life. Specifically, we found that QoL was only measured until the end of life in 1 of the 74 studies assessing QoL among patients with metastatic or incurable cancers. An evaluation of QoL beyond treatment may be especially informative for patients with advanced cancers, because available treatments may offer only marginal survival gains at the expense of potential toxicity or harm.152
Assessing QoL until death is particularly noteworthy, considering only 20% of studies that reported QoL until death also reported improvements in QoL with the treatment. In other words, most studies that assessed QoL until the end of life found no QoL benefit from the intervention. Whereas those that measured QoL during treatment reported QoL improvement from the intervention in 56.7% of studies. Those that reported QoL at other points had a similar percentage of positive findings as those that reported QoL during treatment. These results suggest that the typical length of QoL assessment may be inadequate in fully capturing the full outcome of the intervention on patient QoL.
We found that a high percentage of studies that measured QoL used a drug intervention. While it was beyond the scope of this study to estimate the percentage of drug clinical trials that examine QoL, current estimates from prior research indicate that the frequency of patient-reported outcomes are being increasingly used in registered clinical trials.153 Guidance by the US Food and Drug Administration encouraging better use of patient-reported outcomes in drug clinical trials and professional organizations in oncology proposing standardized approaches to evaluating clinical trial results may be encouraging progress in the number of drug studies reporting on QoL.
To our knowledge, this is the first study to evaluate the points for when QoL assessments were made in oncology trials. Not only do we report whether studies assessed QoL until death, but the numbers we have presented show that there are large differences in most studies between median survival time and median time to follow-up. Our findings that QoL had positive results in 56% of studies are slightly higher than 1 study154 that found that 42% of recently approved oncology drugs improved QoL but are more similar to another study.155 The differences may be because of the types of interventions included in the study and the way that QoL outcomes were coded. It is difficult to know whether these results are true to the total population of patients who receive these interventions or if they only apply to people who do well on these drugs. In many studies, QoL is not measured after a patient has progressed, and because no further QoL measurements are assessed, we do not know the subsequent status of their QoL.
A further consideration in oncology studies is that many drugs being tested in clinical trials do not even report on QoL. Recently, it was reported that almost half of drugs for advanced or metastatic solid tumors being tested in phase 3 trials between 2010 and 2015 do not include a QoL outcome, and for those that do, about a quarter of the studies did not report prespecified QoL outcomes.156 For drugs approved by the Europeans Medicines Agency (2009-2013) that did not show improvement in overall survival during postmarketing studies, only about 11% showed an improvement in QoL.155 Similarly, only 14% of clinical trials registered on ClinicalTrials.gov listed a patient-reported outcome as an outcome of interest.157 For the studies we reviewed, only about 7% reported that QoL was a primary outcome. These results collectively suggest the low priority given to QoL assessments, even though most cancer drugs do not improve patient-centered outcomes, such as overall survival,155,158 and less than half of approved cancer drugs showed improvement in QoL.154 There seems to be discordance between the importance of QoL between researchers and patients, because most patients want to discuss QoL issues with their physicians.159
There are several limitations to our work. First, we only examined articles from the 3 highest-impact oncology journals, which may have limited the generalizability of these findings. Similarly, journals may focus on certain types of outcomes, which may bias the results and make them less generalizable. Second, we used the author’s determination of what was considered an appropriate measurement of QoL, and not all QoL metrics measured the same facets of QoL. Most studies used an established survey from either the European Organisation for Research and Treatment or the Functional Assessment of Cancer Therapy, which are widely used, but some instruments were not as well-validated or only focused on functional or emotional facets of QoL. Third, it was not always clear when QoL assessments were done because of insufficient or unclear reporting of methods. To help limit misclassification, at least 2 reviewers and sometimes 3 independently coded QoL assessments. Finally, QoL measurement may not always be reflective of actual QoL, and we were limited to how each study assessed QoL.
In conclusion, we found that of studies that report on QoL, most assessed QoL during or shortly after the intervention, but few measured QoL until the end of the patient’s life. This is informative because many of the studies that measure QoL until death report worse QoL outcomes for patients in the intervention group, and yet QoL studies with shorter periods measured are increasingly being used for determining health policy decisions.160 To justify a therapy’s use based on improved QoL, it is important to show that a therapy improves QoL across the remainder of a patient’s life and not merely while that patient is receiving treatment. Combination or novel therapies may reduce the benefit of salvage medications and lead to worse QoL after progression, negating QoL gains while on therapy, but this would only be known if studies collect QoL during this time. Future research and policy recommendations should consider not just short-term QoL outcomes but QoL outcomes throughout the patient’s life.
Accepted for Publication: January 13, 2020.
Published: March 4, 2020. doi:10.1001/jamanetworkopen.2020.0363
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Haslam A et al. JAMA Network Open.
Corresponding Author: Alyson Haslam, PhD, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239 (haslama@ohsu.edu).
Author Contributions: Dr Haslam had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Haslam, Prasad.
Acquisition, analysis, or interpretation of data: Haslam, Herrera-Perez, Gill.
Drafting of the manuscript: Haslam.
Critical revision of the manuscript for important intellectual content: Herrera-Perez, Gill, Prasad.
Statistical analysis: Haslam.
Supervision: Prasad.
Conflict of Interest Disclosures: Dr Prasad reports receiving royalties from his book Ending Medical Reversal, an advance for a forthcoming book, Malignant: How Bad Policy and Bad Medicine Work Against Cancer Patients, funding from the Laura and John Arnold Foundation and Arnold Ventures, honoraria for grand rounds and lectures from several universities, medical centers, and professional societies, and payments for writing contributions to Medscape. He has completed uncompensated work at the Veterans Affairs Medical Center in Portland, Oregon, and the Health Technology Assessment Subcommittee of the Oregon Health Authority. Dr Prasad is host of the Plenary Session podcast, which has Patreon backers. No other disclosures were reported.
2.Fojo
T, Mailankody
S, Lo
A. Unintended consequences of expensive cancer therapeutics—the pursuit of marginal indications and a me-too mentality that stifles innovation and creativity: the John Conley Lecture.
JAMA Otolaryngol Head Neck Surg. 2014;140(12):1225-1236. doi:
10.1001/jamaoto.2014.1570PubMedGoogle ScholarCrossref 3.Dreno
B, Thompson
JF, Smithers
BM,
et al. MAGE-A3 immunotherapeutic as adjuvant therapy for patients with resected, MAGE-A3-positive, stage III melanoma (DERMA): a double-blind, randomised, placebo-controlled, phase 3 trial.
Lancet Oncol. 2018;19(7):916-929. doi:
10.1016/S1470-2045(18)30254-7PubMedGoogle ScholarCrossref 4.Clarke
N, Wiechno
P, Alekseev
B,
et al. Olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a randomised, double-blind, placebo-controlled, phase 2 trial.
Lancet Oncol. 2018;19(7):975-986. doi:
10.1016/S1470-2045(18)30365-6PubMedGoogle ScholarCrossref 6.Schäfer
R, Strnad
V, Polgár
C,
et al; Groupe Européen de Curiethérapie of European Society for Radiotherapy and Oncology (GEC-ESTRO). Quality-of-life results for accelerated partial breast irradiation with interstitial brachytherapy versus whole-breast irradiation in early breast cancer after breast-conserving surgery (GEC-ESTRO): 5-year results of a randomised, phase 3 trial.
Lancet Oncol. 2018;19(6):834-844. doi:
10.1016/S1470-2045(18)30195-5PubMedGoogle ScholarCrossref 7.Rimassa
L, Assenat
E, Peck-Radosavljevic
M,
et al. Tivantinib for second-line treatment of MET-high, advanced hepatocellular carcinoma (METIV-HCC): a final analysis of a phase 3, randomised, placebo-controlled study.
Lancet Oncol. 2018;19(5):682-693. doi:
10.1016/S1470-2045(18)30146-3PubMedGoogle ScholarCrossref 8.Iveson
TJ, Kerr
RS, Saunders
MP,
et al. 3 versus 6 months of adjuvant oxaliplatin-fluoropyrimidine combination therapy for colorectal cancer (SCOT): an international, randomised, phase 3, non-inferiority trial.
Lancet Oncol. 2018;19(4):562-578. doi:
10.1016/S1470-2045(18)30093-7PubMedGoogle ScholarCrossref 10.Chi
KN, Protheroe
A, Rodríguez-Antolín
A,
et al. Patient-reported outcomes following abiraterone acetate plus prednisone added to androgen deprivation therapy in patients with newly diagnosed metastatic castration-naive prostate cancer (LATITUDE): an international, randomised phase 3 trial.
Lancet Oncol. 2018;19(2):194-206. doi:
10.1016/S1470-2045(17)30911-7PubMedGoogle ScholarCrossref 11.Hurvitz
SA, Martin
M, Symmans
WF,
et al. Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial.
Lancet Oncol. 2018;19(1):115-126. doi:
10.1016/S1470-2045(17)30716-7PubMedGoogle ScholarCrossref 12.Zhong
W-Z, Wang
Q, Mao
WM,
et al; ADJUVANT investigators. Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II-IIIA (N1-N2)
EGFR-mutant NSCLC (ADJUVANT/CTONG1104): a randomised, open-label, phase 3 study.
Lancet Oncol. 2018;19(1):139-148. doi:
10.1016/S1470-2045(17)30729-5PubMedGoogle ScholarCrossref 13.Colleoni
M, Luo
W, Karlsson
P,
et al; SOLE Investigators. Extended adjuvant intermittent letrozole versus continuous letrozole in postmenopausal women with breast cancer (SOLE): a multicentre, open-label, randomised, phase 3 trial.
Lancet Oncol. 2018;19(1):127-138. doi:
10.1016/S1470-2045(17)30715-5PubMedGoogle ScholarCrossref 14.Brahmer
JR, Rodríguez-Abreu
D, Robinson
AG,
et al. Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced,
PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial.
Lancet Oncol. 2017;18(12):1600-1609. doi:
10.1016/S1470-2045(17)30690-3PubMedGoogle ScholarCrossref 15.Bang
Y-J, Xu
RH, Chin
K,
et al. Olaparib in combination with paclitaxel in patients with advanced gastric cancer who have progressed following first-line therapy (GOLD): a double-blind, randomised, placebo-controlled, phase 3 trial.
Lancet Oncol. 2017;18(12):1637-1651. doi:
10.1016/S1470-2045(17)30682-4PubMedGoogle ScholarCrossref 16.Vilgrain
V, Pereira
H, Assenat
E,
et al; SARAH Trial Group. Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial.
Lancet Oncol. 2017;18(12):1624-1636. doi:
10.1016/S1470-2045(17)30683-6PubMedGoogle ScholarCrossref 17.Wu
Y-L, Cheng
Y, Zhou
X,
et al. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial.
Lancet Oncol. 2017;18(11):1454-1466. doi:
10.1016/S1470-2045(17)30608-3PubMedGoogle ScholarCrossref 18.Seddon
B, Strauss
SJ, Whelan
J,
et al. Gemcitabine and docetaxel versus doxorubicin as first-line treatment in previously untreated advanced unresectable or metastatic soft-tissue sarcomas (GeDDiS): a randomised controlled phase 3 trial.
Lancet Oncol. 2017;18(10):1397-1410. doi:
10.1016/S1470-2045(17)30622-8PubMedGoogle ScholarCrossref 19.Weller
M, Butowski
N, Tran
DD,
et al; ACT IV trial investigators. Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial.
Lancet Oncol. 2017;18(10):1373-1385. doi:
10.1016/S1470-2045(17)30517-XPubMedGoogle ScholarCrossref 20.Pavel
ME, Singh
S, Strosberg
JR,
et al. Health-related quality of life for everolimus versus placebo in patients with advanced, non-functional, well-differentiated gastrointestinal or lung neuroendocrine tumours (RADIANT-4): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.
Lancet Oncol. 2017;18(10):1411-1422. doi:
10.1016/S1470-2045(17)30471-0PubMedGoogle ScholarCrossref 21.Kim
S-B, Dent
R, Im
SA,
et al; LOTUS investigators. Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.
Lancet Oncol. 2017;18(10):1360-1372. doi:
10.1016/S1470-2045(17)30450-3PubMedGoogle ScholarCrossref 22.Alderson
D, Cunningham
D, Nankivell
M,
et al. Neoadjuvant cisplatin and fluorouracil versus epirubicin, cisplatin, and capecitabine followed by resection in patients with oesophageal adenocarcinoma (UK MRC OE05): an open-label, randomised phase 3 trial.
Lancet Oncol. 2017;18(9):1249-1260. doi:
10.1016/S1470-2045(17)30447-3PubMedGoogle ScholarCrossref 23.Duchesne
GM, Woo
HH, King
M,
et al. Health-related quality of life for immediate versus delayed androgen-deprivation therapy in patients with asymptomatic, non-curable prostate cancer (TROG 03.06 and VCOG PR 01-03 [TOAD]): a randomised, multicentre, non-blinded, phase 3 trial.
Lancet Oncol. 2017;18(9):1192-1201. doi:
10.1016/S1470-2045(17)30426-6PubMedGoogle ScholarCrossref 24.Pujade-Lauraine
E, Ledermann
JA, Selle
F,
et al; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a
BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial.
Lancet Oncol. 2017;18(9):1274-1284. doi:
10.1016/S1470-2045(17)30469-2PubMedGoogle ScholarCrossref 25.Maio
M, Scherpereel
A, Calabrò
L,
et al. Tremelimumab as second-line or third-line treatment in relapsed malignant mesothelioma (DETERMINE): a multicentre, international, randomised, double-blind, placebo-controlled phase 2b trial.
Lancet Oncol. 2017;18(9):1261-1273. doi:
10.1016/S1470-2045(17)30446-1PubMedGoogle ScholarCrossref 26.Brown
PD, Ballman
KV, Cerhan
JH,
et al. Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial.
Lancet Oncol. 2017;18(8):1049-1060. doi:
10.1016/S1470-2045(17)30441-2PubMedGoogle ScholarCrossref 27.Harrington
KJ, Ferris
RL, Blumenschein
G
Jr,
et al. Nivolumab versus standard, single-agent therapy of investigator’s choice in recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141): health-related quality-of-life results from a randomised, phase 3 trial.
Lancet Oncol. 2017;18(8):1104-1115. doi:
10.1016/S1470-2045(17)30421-7PubMedGoogle ScholarCrossref 28.Tap
WD, Papai
Z, Van Tine
BA,
et al. Doxorubicin plus evofosfamide versus doxorubicin alone in locally advanced, unresectable or metastatic soft-tissue sarcoma (TH CR-406/SARC021): an international, multicentre, open-label, randomised phase 3 trial.
Lancet Oncol. 2017;18(8):1089-1103. doi:
10.1016/S1470-2045(17)30381-9PubMedGoogle ScholarCrossref 29.Shaw
AT, Kim
TM, Crinò
L,
et al. Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomised, controlled, open-label, phase 3 trial.
Lancet Oncol. 2017;18(7):874-886. doi:
10.1016/S1470-2045(17)30339-XPubMedGoogle ScholarCrossref 30.Cameron
D, Morden
JP, Canney
P,
et al; TACT2 Investigators. Accelerated versus standard epirubicin followed by cyclophosphamide, methotrexate, and fluorouracil or capecitabine as adjuvant therapy for breast cancer in the randomised UK TACT2 trial (CRUK/05/19): a multicentre, phase 3, open-label, randomised, controlled trial.
Lancet Oncol. 2017;18(7):929-945. doi:
10.1016/S1470-2045(17)30404-7PubMedGoogle ScholarCrossref 31.Coleman
RL, Brady
MF, Herzog
TJ,
et al. Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial.
Lancet Oncol. 2017;18(6):779-791. doi:
10.1016/S1470-2045(17)30279-6PubMedGoogle ScholarCrossref 33.Coens
C, Suciu
S, Chiarion-Sileni
V,
et al. Health-related quality of life with adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): secondary outcomes of a multinational, randomised, double-blind, phase 3 trial.
Lancet Oncol. 2017;18(3):393-403. doi:
10.1016/S1470-2045(17)30015-3PubMedGoogle ScholarCrossref 34.Soulières
D, Faivre
S, Mesía
R,
et al. Buparlisib and paclitaxel in patients with platinum-pretreated recurrent or metastatic squamous cell carcinoma of the head and neck (BERIL-1): a randomised, double-blind, placebo-controlled phase 2 trial.
Lancet Oncol. 2017;18(3):323-335. doi:
10.1016/S1470-2045(17)30064-5PubMedGoogle ScholarCrossref 36.Azzouzi
A-R, Vincendeau
S, Barret
E,
et al; PCM301 Study Group. Padeliporfin vascular-targeted photodynamic therapy versus active surveillance in men with low-risk prostate cancer (CLIN1001 PCM301): an open-label, phase 3, randomised controlled trial.
Lancet Oncol. 2017;18(2):181-191. doi:
10.1016/S1470-2045(16)30661-1PubMedGoogle ScholarCrossref 39.Ascierto
PA, McArthur
GA, Dréno
B,
et al. Cobimetinib combined with vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial.
Lancet Oncol. 2016;17(9):1248-1260. doi:
10.1016/S1470-2045(16)30122-XPubMedGoogle ScholarCrossref 40.de Boer
SM, Powell
ME, Mileshkin
L,
et al; PORTEC study group. Toxicity and quality of life after adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): an open-label, multicentre, randomised, phase 3 trial.
Lancet Oncol. 2016;17(8):1114-1126. doi:
10.1016/S1470-2045(16)30120-6PubMedGoogle ScholarCrossref 41.Clive
AO, Taylor
H, Dobson
L,
et al. Prophylactic radiotherapy for the prevention of procedure-tract metastases after surgical and large-bore pleural procedures in malignant pleural mesothelioma (SMART): a multicentre, open-label, phase 3, randomised controlled trial.
Lancet Oncol. 2016;17(8):1094-1104. doi:
10.1016/S1470-2045(16)30095-XPubMedGoogle ScholarCrossref 43.Carrie
C, Hasbini
A, de Laroche
G,
et al. Salvage radiotherapy with or without short-term hormone therapy for rising prostate-specific antigen concentration after radical prostatectomy (GETUG-AFU 16): a randomised, multicentre, open-label phase 3 trial.
Lancet Oncol. 2016;17(6):747-756. doi:
10.1016/S1470-2045(16)00111-XPubMedGoogle ScholarCrossref 44.Bendixen
M, Jørgensen
OD, Kronborg
C, Andersen
C, Licht
PB. Postoperative pain and quality of life after lobectomy via video-assisted thoracoscopic surgery or anterolateral thoracotomy for early stage lung cancer: a randomised controlled trial.
Lancet Oncol. 2016;17(6):836-844. doi:
10.1016/S1470-2045(16)00173-XPubMedGoogle ScholarCrossref 45.Duchesne
GM, Woo
HH, Bassett
JK,
et al. Timing of androgen-deprivation therapy in patients with prostate cancer with a rising PSA (TROG 03.06 and VCOG PR 01-03 [TOAD]): a randomised, multicentre, non-blinded, phase 3 trial.
Lancet Oncol. 2016;17(6):727-737. doi:
10.1016/S1470-2045(16)00107-8PubMedGoogle ScholarCrossref 46.Vansteenkiste
JF, Cho
BC, Vanakesa
T,
et al. Efficacy of the MAGE-A3 cancer immunotherapeutic as adjuvant therapy in patients with resected MAGE-A3-positive non-small-cell lung cancer (MAGRIT): a randomised, double-blind, placebo-controlled, phase 3 trial.
Lancet Oncol. 2016;17(6):822-835. doi:
10.1016/S1470-2045(16)00099-1PubMedGoogle ScholarCrossref 47.Park
K, Tan
EH, O’Byrne
K,
et al. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial.
Lancet Oncol. 2016;17(5):577-589. doi:
10.1016/S1470-2045(16)30033-XPubMedGoogle ScholarCrossref 48.Trněný
M, Lamy
T, Walewski
J,
et al; SPRINT trial investigators and in collaboration with the European Mantle Cell Lymphoma Network. Lenalidomide versus investigator’s choice in relapsed or refractory mantle cell lymphoma (MCL-002; SPRINT): a phase 2, randomised, multicentre trial.
Lancet Oncol. 2016;17(3):319-331. doi:
10.1016/S1470-2045(15)00559-8PubMedGoogle ScholarCrossref 49.Chan
A, Delaloge
S, Holmes
FA,
et al; ExteNET Study Group. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.
Lancet Oncol. 2016;17(3):367-377. doi:
10.1016/S1470-2045(15)00551-3PubMedGoogle ScholarCrossref 51.Walker
I, Panzarella
T, Couban
S,
et al; Canadian Blood and Marrow Transplant Group. Pretreatment with anti-thymocyte globulin versus no anti-thymocyte globulin in patients with haematological malignancies undergoing haemopoietic cell transplantation from unrelated donors: a randomised, controlled, open-label, phase 3, multicentre trial.
Lancet Oncol. 2016;17(2):164-173. doi:
10.1016/S1470-2045(15)00462-3PubMedGoogle ScholarCrossref 53.Takashima
T, Mukai
H, Hara
F,
et al; SELECT BC Study Group. Taxanes versus S-1 as the first-line chemotherapy for metastatic breast cancer (SELECT BC): an open-label, non-inferiority, randomised phase 3 trial.
Lancet Oncol. 2016;17(1):90-98. doi:
10.1016/S1470-2045(15)00411-8PubMedGoogle ScholarCrossref 54.du Bois
A, Kristensen
G, Ray-Coquard
I,
et al; AGO Study Group led Gynecologic Cancer Intergroup/European Network of Gynaecologic Oncology Trials Groups Intergroup Consortium. Standard first-line chemotherapy with or without nintedanib for advanced ovarian cancer (AGO-OVAR 12): a randomised, double-blind, placebo-controlled phase 3 trial.
Lancet Oncol. 2016;17(1):78-89. doi:
10.1016/S1470-2045(15)00366-6PubMedGoogle ScholarCrossref 55.Place
AE, Stevenson
KE, Vrooman
LM,
et al. Intravenous pegylated asparaginase versus intramuscular native Escherichia coli L-asparaginase in newly diagnosed childhood acute lymphoblastic leukaemia (DFCI 05-001): a randomised, open-label phase 3 trial.
Lancet Oncol. 2015;16(16):1677-1690. doi:
10.1016/S1470-2045(15)00363-0PubMedGoogle ScholarCrossref 56.Stahel
RA, Riesterer
O, Xyrafas
A,
et al. Neoadjuvant chemotherapy and extrapleural pneumonectomy of malignant pleural mesothelioma with or without hemithoracic radiotherapy (SAKK 17/04): a randomised, international, multicentre phase 2 trial.
Lancet Oncol. 2015;16(16):1651-1658. doi:
10.1016/S1470-2045(15)00208-9PubMedGoogle ScholarCrossref 57.Wilkins
A, Mossop
H, Syndikus
I,
et al. Hypofractionated radiotherapy versus conventionally fractionated radiotherapy for patients with intermediate-risk localised prostate cancer: 2-year patient-reported outcomes of the randomised, non-inferiority, phase 3 CHHiP trial.
Lancet Oncol. 2015;16(16):1605-1616. doi:
10.1016/S1470-2045(15)00280-6PubMedGoogle ScholarCrossref 58.Chow
E, Meyer
RM, Ding
K,
et al. Dexamethasone in the prophylaxis of radiation-induced pain flare after palliative radiotherapy for bone metastases: a double-blind, randomised placebo-controlled, phase 3 trial.
Lancet Oncol. 2015;16(15):1463-1472. doi:
10.1016/S1470-2045(15)00199-0PubMedGoogle ScholarCrossref 59.Perez
EA, Awada
A, O’Shaughnessy
J,
et al. Etirinotecan pegol (NKTR-102) versus treatment of physician’s choice in women with advanced breast cancer previously treated with an anthracycline, a taxane, and capecitabine (BEACON): a randomised, open-label, multicentre, phase 3 trial.
Lancet Oncol. 2015;16(15):1556-1568. doi:
10.1016/S1470-2045(15)00332-0PubMedGoogle ScholarCrossref 60.Symonds
RP, Gourley
C, Davidson
S,
et al. Cediranib combined with carboplatin and paclitaxel in patients with metastatic or recurrent cervical cancer (CIRCCa): a randomised, double-blind, placebo-controlled phase 2 trial.
Lancet Oncol. 2015;16(15):1515-1524. doi:
10.1016/S1470-2045(15)00220-XPubMedGoogle ScholarCrossref 61.Grob
JJ, Amonkar
MM, Karaszewska
B,
et al. Comparison of dabrafenib and trametinib combination therapy with vemurafenib monotherapy on health-related quality of life in patients with unresectable or metastatic cutaneous BRAF Val600-mutation-positive melanoma (COMBI-v): results of a phase 3, open-label, randomised trial.
Lancet Oncol. 2015;16(13):1389-1398. doi:
10.1016/S1470-2045(15)00087-XPubMedGoogle ScholarCrossref 62.Burnett
AK, Russell
NH, Hills
RK,
et al; UK National Cancer Research Institute Acute Myeloid Leukaemia Working Group. Arsenic trioxide and all-trans retinoic acid treatment for acute promyelocytic leukaemia in all risk groups (AML17): results of a randomised, controlled, phase 3 trial.
Lancet Oncol. 2015;16(13):1295-1305. doi:
10.1016/S1470-2045(15)00193-XPubMedGoogle ScholarCrossref 63.van Oers
MHJ, Kuliczkowski
K, Smolej
L,
et al; PROLONG study investigators. Ofatumumab maintenance versus observation in relapsed chronic lymphocytic leukaemia (PROLONG): an open-label, multicentre, randomised phase 3 study.
Lancet Oncol. 2015;16(13):1370-1379. doi:
10.1016/S1470-2045(15)00143-6PubMedGoogle ScholarCrossref 64.Hegewisch-Becker
S, Graeven
U, Lerchenmüller
CA,
et al. Maintenance strategies after first-line oxaliplatin plus fluoropyrimidine plus bevacizumab for patients with metastatic colorectal cancer (AIO 0207): a randomised, non-inferiority, open-label, phase 3 trial.
Lancet Oncol. 2015;16(13):1355-1369. doi:
10.1016/S1470-2045(15)00042-XPubMedGoogle ScholarCrossref 65.Henderson
MA, Burmeister
BH, Ainslie
J,
et al. Adjuvant lymph-node field radiotherapy versus observation only in patients with melanoma at high risk of further lymph-node field relapse after lymphadenectomy (ANZMTG 01.02/TROG 02.01): 6-year follow-up of a phase 3, randomised controlled trial.
Lancet Oncol. 2015;16(9):1049-1060. doi:
10.1016/S1470-2045(15)00187-4PubMedGoogle ScholarCrossref 66.Soria
J-C, Wu
YL, Nakagawa
K,
et al. Gefitinib plus chemotherapy versus placebo plus chemotherapy in EGFR-mutation-positive non-small-cell lung cancer after progression on first-line gefitinib (IMPRESS): a phase 3 randomised trial.
Lancet Oncol. 2015;16(8):990-998. doi:
10.1016/S1470-2045(15)00121-7PubMedGoogle ScholarCrossref 67.Soria
J-C, Felip
E, Cobo
M,
et al; LUX-Lung 8 Investigators. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial.
Lancet Oncol. 2015;16(8):897-907. doi:
10.1016/S1470-2045(15)00006-6PubMedGoogle ScholarCrossref 68.Lee
CK, Novello
S, Rydén
A, Mann
H, Mok
T. Patient-reported symptoms and impact of treatment with osimertinib versus chemotherapy in advanced non-small-cell lung cancer: the AURA3 trial.
J Clin Oncol. 2018;36(18):1853-1860. doi:
10.1200/JCO.2017.77.2293PubMedGoogle ScholarCrossref 69.Strosberg
J, Wolin
E, Chasen
B,
et al; NETTER-1 Study Group. Health-related quality of life in patients with progressive midgut neuroendocrine tumors treated with
177Lu-dotatate in the phase III NETTER-1 trial.
J Clin Oncol. 2018;36(25):2578-2584. doi:
10.1200/JCO.2018.78.5865PubMedGoogle ScholarCrossref 70.Vaughn
DJ, Bellmunt
J, Fradet
Y,
et al. Health-related quality-of-life analysis from KEYNOTE-045: a phase III study of pembrolizumab versus chemotherapy for previously treated advanced urothelial cancer.
J Clin Oncol. 2018;36(16):1579-1587. doi:
10.1200/JCO.2017.76.9562PubMedGoogle ScholarCrossref 71.De Ruysscher
D, Dingemans
AC, Praag
J,
et al. Prophylactic cranial irradiation versus observation in radically treated stage III non-small-cell lung cancer: a randomized phase III NVALT-11/DLCRG-02 study.
J Clin Oncol. 2018;36(23):2366-2377. doi:
10.1200/JCO.2017.77.5817PubMedGoogle ScholarCrossref 72.Porceddu
SV, Bressel
M, Poulsen
MG,
et al. Postoperative concurrent chemoradiotherapy versus postoperative radiotherapy in high-risk cutaneous squamous cell carcinoma of the head and neck: the randomized phase III TROG 05.01 trial.
J Clin Oncol. 2018;36(13):1275-1283. doi:
10.1200/JCO.2017.77.0941PubMedGoogle ScholarCrossref 73.Morgans
AK, Chen
YH, Sweeney
CJ,
et al. Quality of life during treatment with chemohormonal therapy: analysis of E3805 chemohormonal androgen ablation randomized trial in prostate cancer.
J Clin Oncol. 2018;36(11):1088-1095. doi:
10.1200/JCO.2017.75.3335PubMedGoogle ScholarCrossref 74.Ito
Y, Tsuda
T, Minatogawa
H,
et al. Placebo-controlled, double-blinded phase iii study comparing dexamethasone on day 1 with dexamethasone on days 1 to 3 with combined neurokinin-1 receptor antagonist and palonosetron in high-emetogenic chemotherapy.
J Clin Oncol. 2018;36(10):1000-1006. doi:
10.1200/JCO.2017.74.4375PubMedGoogle ScholarCrossref 76.Johnston
SRD, Hegg
R, Im
SA,
et al. Phase III, randomized study of dual human epidermal growth factor receptor 2 (HER2) blockade with lapatinib plus trastuzumab in combination with an aromatase inhibitor in postmenopausal women with HER2-positive, hormone receptor-positive metastatic breast cancer: ALTERNATIVE.
J Clin Oncol. 2018;36(8):741-748. doi:
10.1200/JCO.2017.74.7824PubMedGoogle ScholarCrossref 77.Cella
D, Escudier
B, Tannir
NM,
et al. Quality of life outcomes for cabozantinib versus everolimus in patients with metastatic renal cell carcinoma: METEOR phase III randomized trial.
J Clin Oncol. 2018;36(8):757-764. doi:
10.1200/JCO.2017.75.2170PubMedGoogle ScholarCrossref 78.Aparicio
T, Ghiringhelli
F, Boige
V,
et al; PRODIGE 9 Investigators. Bevacizumab maintenance versus no maintenance during chemotherapy-free intervals in metastatic colorectal cancer: a randomized phase III trial (PRODIGE 9).
J Clin Oncol. 2018;36(7):674-681. doi:
10.1200/JCO.2017.75.2931PubMedGoogle ScholarCrossref 80.Ost
P, Reynders
D, Decaestecker
K,
et al. Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence: a prospective, randomized, multicenter phase II trial.
J Clin Oncol. 2018;36(5):446-453. doi:
10.1200/JCO.2017.75.4853PubMedGoogle ScholarCrossref 81.Larkin
J, Minor
D, D’Angelo
S,
et al. Overall survival in patients with advanced melanoma who received nivolumab versus investigator’s choice chemotherapy in CheckMate 037: a randomized, controlled, open-label phase III trial.
J Clin Oncol. 2018;36(4):383-390. doi:
10.1200/JCO.2016.71.8023PubMedGoogle ScholarCrossref 82.Henry
NL, Unger
JM, Schott
AF,
et al. Randomized, multicenter, placebo-controlled clinical trial of duloxetine versus placebo for aromatase inhibitor-associated arthralgias in early-stage breast cancer: SWOG S1202.
J Clin Oncol. 2018;36(4):326-332. doi:
10.1200/JCO.2017.74.6651PubMedGoogle ScholarCrossref 83.Noordman
BJ, Verdam
MGE, Lagarde
SM,
et al. Effect of neoadjuvant chemoradiotherapy on health-related quality of life in esophageal or junctional cancer: results from the randomized CROSS trial.
J Clin Oncol. 2018;36(3):268-275. doi:
10.1200/JCO.2017.73.7718PubMedGoogle ScholarCrossref 84.Motzer
RJ, Haas
NB, Donskov
F,
et al; PROTECT investigators. Randomized phase III trial of adjuvant pazopanib versus placebo after nephrectomy in patients with localized or locally advanced renal cell carcinoma.
J Clin Oncol. 2017;35(35):3916-3923. doi:
10.1200/JCO.2017.73.5324PubMedGoogle ScholarCrossref 85.Zhang
L, Qu
X, Teng
Y,
et al. Efficacy of thalidomide in preventing delayed nausea and vomiting induced by highly emetogenic chemotherapy: a randomized, multicenter, double-blind, placebo-controlled phase III trial (CLOG1302 study).
J Clin Oncol. 2017;35(31):3558-3565. doi:
10.1200/JCO.2017.72.2538PubMedGoogle ScholarCrossref 86.Pignata
S, Scambia
G, Bologna
A,
et al. Randomized controlled trial testing the efficacy of platinum-free interval prolongation in advanced ovarian cancer: the MITO-8, MaNGO, BGOG-Ov1, AGO-Ovar2.16, ENGOT-Ov1, GCIG study.
J Clin Oncol. 2017;35(29):3347-3353. doi:
10.1200/JCO.2017.73.4293PubMedGoogle ScholarCrossref 87.Oudard
S, Fizazi
K, Sengeløv
L,
et al. Cabazitaxel versus docetaxel as first-line therapy for patients with metastatic castration-resistant prostate cancer: a randomized phase III trial—FIRSTANA.
J Clin Oncol. 2017;35(28):3189-3197. doi:
10.1200/JCO.2016.72.1068PubMedGoogle ScholarCrossref 88.Eisenberger
M, Hardy-Bessard
AC, Kim
CS,
et al; Phase III Study Comparing a Reduced Dose of Cabazitaxel. Phase III study comparing a reduced dose of cabazitaxel (20 mg/m
2) and the currently approved dose (25 mg/m
2) in postdocetaxel patients with metastatic castration-resistant prostate cancer—PROSELICA.
J Clin Oncol. 2017;35(28):3198-3206. doi:
10.1200/JCO.2016.72.1076PubMedGoogle ScholarCrossref 89.Kim
D-W, Tiseo
M, Ahn
MJ,
et al. Brigatinib in patients with crizotinib-refractory anaplastic lymphoma kinase-positive non-small-cell lung cancer: a randomized, multicenter phase II trial.
J Clin Oncol. 2017;35(22):2490-2498. doi:
10.1200/JCO.2016.71.5904PubMedGoogle ScholarCrossref 91.Agarwala
SS, Lee
SJ, Yip
W,
et al. Phase III randomized study of 4 weeks of high-dose interferon-α-2b in stage T2bNO, T3a-bNO, T4a-bNO, and T1-4N1a-2a (microscopic) melanoma: a trial of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group (E1697).
J Clin Oncol. 2017;35(8):885-892. doi:
10.1200/JCO.2016.70.2951PubMedGoogle ScholarCrossref 92.Platzbecker
U, Avvisati
G, Cicconi
L,
et al. Improved outcomes with retinoic acid and arsenic trioxide compared with retinoic acid and chemotherapy in non-high-risk acute promyelocytic leukemia: final results of the randomized Italian-German APL0406 trial.
J Clin Oncol. 2017;35(6):605-612. doi:
10.1200/JCO.2016.67.1982PubMedGoogle ScholarCrossref 93.Lee
SM, Falzon
M, Blackhall
F,
et al. Randomized prospective biomarker trial of ercc1 for comparing platinum and nonplatinum therapy in advanced non-small-cell lung cancer: ERCC1 trial (ET).
J Clin Oncol. 2017;35(4):402-411. doi:
10.1200/JCO.2016.68.1841PubMedGoogle ScholarCrossref 94.Perez
EA, Barrios
C, Eiermann
W,
et al. Trastuzumab emtansine with or without pertuzumab versus trastuzumab plus taxane for human epidermal growth factor receptor 2-positive, advanced breast cancer: primary results from the phase III MARIANNE study.
J Clin Oncol. 2017;35(2):141-148. doi:
10.1200/JCO.2016.67.4887PubMedGoogle ScholarCrossref 96.Liu
JF, Ray-Coquard
I, Selle
F,
et al. Randomized phase II trial of seribantumab in combination with paclitaxel in patients with advanced platinum-resistant or -refractory ovarian cancer.
J Clin Oncol. 2016;34(36):4345-4353. doi:
10.1200/JCO.2016.67.1891PubMedGoogle ScholarCrossref 97.Stewart
AK, Dimopoulos
MA, Masszi
T,
et al. Health-related quality-of-life results from the open-label, randomized, phase III ASPIRE trial evaluating carfilzomib, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone in patients with relapsed multiple myeloma.
J Clin Oncol. 2016;34(32):3921-3930. doi:
10.1200/JCO.2016.66.9648PubMedGoogle ScholarCrossref 98.Gill
S, Ko
YJ, Cripps
C,
et al. PANCREOX: a randomized phase III study of fluorouracil/leucovorin with or without oxaliplatin for second-line advanced pancreatic cancer in patients who have received gemcitabine-based chemotherapy.
J Clin Oncol. 2016;34(32):3914-3920. doi:
10.1200/JCO.2016.68.5776PubMedGoogle ScholarCrossref 99.Hulin
C, Belch
A, Shustik
C,
et al. Updated outcomes and impact of age with lenalidomide and low-dose dexamethasone or melphalan, prednisone, and thalidomide in the randomized, phase III FIRST trial.
J Clin Oncol. 2016;34(30):3609-3617. doi:
10.1200/JCO.2016.66.7295PubMedGoogle ScholarCrossref 100.Santini
V, Almeida
A, Giagounidis
A,
et al; Randomized Phase III Study of Lenalidomide Versus Placebo in RBC Transfusion-Dependent Patients With Lower-Risk Non-del. Randomized phase III study of lenalidomide versus placebo in RBC transfusion-dependent patients with lower-risk Non-del(5q) myelodysplastic syndromes and ineligible for or refractory to erythropoiesis-stimulating agents.
J Clin Oncol. 2016;34(25):2988-2996. doi:
10.1200/JCO.2015.66.0118PubMedGoogle ScholarCrossref 103.Segelov
E, Thavaneswaran
S, Waring
PM,
et al. Response to cetuximab with or without irinotecan in patients with refractory metastatic colorectal cancer harboring the KRAS G13D mutation: Australasian Gastro-Intestinal Trials Group ICECREAM study.
J Clin Oncol. 2016;34(19):2258-2264. doi:
10.1200/JCO.2015.65.6843PubMedGoogle ScholarCrossref 105.Bolla
M, Maingon
P, Carrie
C,
et al. Short androgen suppression and radiation dose escalation for intermediate- and high-risk localized prostate cancer: results of EORTC trial 22991.
J Clin Oncol. 2016;34(15):1748-1756. doi:
10.1200/JCO.2015.64.8055PubMedGoogle ScholarCrossref 106.Herrlinger
U, Schäfer
N, Steinbach
JP,
et al. Bevacizumab plus irinotecan versus temozolomide in newly diagnosed O6-methylguanine-DNA methyltransferase nonmethylated glioblastoma: the randomized GLARIUS trial.
J Clin Oncol. 2016;34(14):1611-1619. doi:
10.1200/JCO.2015.63.4691PubMedGoogle ScholarCrossref 107.Ribi
K, Luo
W, Bernhard
J,
et al. Adjuvant tamoxifen plus ovarian function suppression versus tamoxifen alone in premenopausal women with early breast cancer: patient-reported outcomes in the Suppression of Ovarian Function trial.
J Clin Oncol. 2016;34(14):1601-1610. doi:
10.1200/JCO.2015.64.8675PubMedGoogle ScholarCrossref 108.Corre
R, Greillier
L, Le Caër
H,
et al. Use of a comprehensive geriatric assessment for the management of elderly patients with advanced non-small-cell lung cancer: the phase III randomized ESOGIA-GFPC-GECP 08-02 study.
J Clin Oncol. 2016;34(13):1476-1483. doi:
10.1200/JCO.2015.63.5839PubMedGoogle ScholarCrossref 109.Li
J, Qin
S, Xu
J,
et al. Randomized, double-blind, placebo-controlled phase III trial of apatinib in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction.
J Clin Oncol. 2016;34(13):1448-1454. doi:
10.1200/JCO.2015.63.5995PubMedGoogle ScholarCrossref 110.Melosky
B, Anderson
H, Burkes
RL,
et al. Pan Canadian rash trial: a randomized phase III trial evaluating the impact of a prophylactic skin treatment regimen on epidermal growth factor receptor-tyrosine kinase inhibitor-induced skin toxicities in patients with metastatic lung cancer.
J Clin Oncol. 2016;34(8):810-815. doi:
10.1200/JCO.2015.62.3918PubMedGoogle ScholarCrossref 111.Pujade-Lauraine
E, Selle
F, Weber
B,
et al. Volasertib versus chemotherapy in platinum-resistant or -refractory ovarian cancer: a randomized phase II Groupe des Investigateurs Nationaux pour l’Etude des Cancers de l’Ovaire Study.
J Clin Oncol. 2016;34(7):706-713. doi:
10.1200/JCO.2015.62.1474PubMedGoogle ScholarCrossref 113.Hecht
JR, Bang
YJ, Qin
SK,
et al. Lapatinib in combination with capecitabine plus oxaliplatin in human epidermal growth factor receptor 2-positive advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma: TRIO-013/LOGiC—a randomized phase III trial.
J Clin Oncol. 2016;34(5):443-451. doi:
10.1200/JCO.2015.62.6598PubMedGoogle ScholarCrossref 115.Harrington
K, Temam
S, Mehanna
H,
et al. Postoperative adjuvant lapatinib and concurrent chemoradiotherapy followed by maintenance lapatinib monotherapy in high-risk patients with resected squamous cell carcinoma of the head and neck: a phase III, randomized, double-blind, placebo-controlled study.
J Clin Oncol. 2015;33(35):4202-4209. doi:
10.1200/JCO.2015.61.4370PubMedGoogle ScholarCrossref 116.Ghadjar
P, Hayoz
S, Bernhard
J,
et al. Acute toxicity and quality of life after dose-intensified salvage radiation therapy for biochemically recurrent prostate cancer after prostatectomy: first results of the randomized trial SAKK 09/10.
J Clin Oncol. 2015;33(35):4158-4166. doi:
10.1200/JCO.2015.63.3529PubMedGoogle ScholarCrossref 117.Mohr
P, Hauschild
A, Trefzer
U,
et al. Intermittent high-dose intravenous interferon alfa-2b for adjuvant treatment of stage III melanoma: final analysis of a randomized phase III Dermatologic Cooperative Oncology Group trial.
J Clin Oncol. 2015;33(34):4077-4084. doi:
10.1200/JCO.2014.59.6932PubMedGoogle ScholarCrossref 118.Hurwitz
HI, Uppal
N, Wagner
SA,
et al. Randomized, double-blind, phase II study of ruxolitinib or placebo in combination with capecitabine in patients with metastatic pancreatic cancer for whom therapy with gemcitabine has failed.
J Clin Oncol. 2015;33(34):4039-4047. doi:
10.1200/JCO.2015.61.4578PubMedGoogle ScholarCrossref 120.Borget
I, Bonastre
J, Catargi
B,
et al. Quality of life and cost-effectiveness assessment of radioiodine ablation strategies in patients with thyroid cancer: results from the randomized phase III ESTIMABL trial.
J Clin Oncol. 2015;33(26):2885-2892. doi:
10.1200/JCO.2015.61.6722PubMedGoogle ScholarCrossref 121.Hofheinz
R-D, Gencer
D, Schulz
H,
et al. Mapisal versus urea cream as prophylaxis for capecitabine-associated hand-foot syndrome: a randomized phase III trial of the AIO Quality of Life Working Group.
J Clin Oncol. 2015;33(22):2444-2449. doi:
10.1200/JCO.2014.60.4587PubMedGoogle ScholarCrossref 122.Brundage
M, Sydes
MR, Parulekar
WR,
et al. Impact of radiotherapy when added to androgen-deprivation therapy for locally advanced prostate cancer: long-term quality-of-life outcomes from the NCIC CTG PR3/MRC PR07 randomized trial.
J Clin Oncol. 2015;33(19):2151-2157. doi:
10.1200/JCO.2014.57.8724PubMedGoogle ScholarCrossref 123.Taphoorn
MJB, Henriksson
R, Bottomley
A,
et al. Health-related quality of life in a randomized phase III study of bevacizumab, temozolomide, and radiotherapy in newly diagnosed glioblastoma.
J Clin Oncol. 2015;33(19):2166-2175. doi:
10.1200/JCO.2014.60.3217PubMedGoogle ScholarCrossref 124.Taphoorn
MJB, Dirven
L, Kanner
AA,
et al. Influence of treatment with tumor-treating fields on health-related quality of life of patients with newly diagnosed glioblastoma: a secondary analysis of a randomized clinical trial.
JAMA Oncol. 2018;4(4):495-504. doi:
10.1001/jamaoncol.2017.5082PubMedGoogle ScholarCrossref 125.Cirkel
GA, Hamberg
P, Sleijfer
S,
et al; Dutch WIN-O Consortium. Alternating treatment with pazopanib and everolimus vs continuous pazopanib to delay disease progression in patients with metastatic clear cell renal cell cancer: the ROPETAR randomized clinical trial.
JAMA Oncol. 2017;3(4):501-508. doi:
10.1001/jamaoncol.2016.5202PubMedGoogle ScholarCrossref 126.Melisko
ME, Goldman
ME, Hwang
J,
et al. Vaginal testosterone cream vs estradiol vaginal ring for vaginal dryness or decreased libido in women receiving aromatase inhibitors for early-stage breast cancer: a randomized clinical trial.
JAMA Oncol. 2017;3(3):313-319. doi:
10.1001/jamaoncol.2016.3904PubMedGoogle ScholarCrossref 127.Siu
LL, Waldron
JN, Chen
BE,
et al. Effect of standard radiotherapy with cisplatin vs accelerated radiotherapy with panitumumab in locoregionally advanced squamous cell head and neck carcinoma: a randomized clinical trial.
JAMA Oncol. 2017;3(2):220-226. doi:
10.1001/jamaoncol.2016.4510PubMedGoogle ScholarCrossref 128.Awada
A, Colomer
R, Inoue
K,
et al. Neratinib plus paclitaxel vs trastuzumab plus paclitaxel in previously untreated metastatic
ERBB2-positive breast cancer: the NEfERT-T randomized clinical trial.
JAMA Oncol. 2016;2(12):1557-1564. doi:
10.1001/jamaoncol.2016.0237PubMedGoogle ScholarCrossref 129.Movsas
B, Hu
C, Sloan
J,
et al. Quality of life analysis of a radiation dose-escalation study of patients with non-small-cell lung cancer: a secondary analysis of the Radiation Therapy Oncology Group 0617 randomized clinical trial.
JAMA Oncol. 2016;2(3):359-367. doi:
10.1001/jamaoncol.2015.3969PubMedGoogle ScholarCrossref 134.El-Jawahri
A, Traeger
L, Greer
JA,
et al. Effect of inpatient palliative care during hematopoietic stem-cell transplant on psychological distress 6 months after transplant: results of a randomized clinical trial.
J Clin Oncol. 2017;35(32):3714-3721. doi:
10.1200/JCO.2017.73.2800PubMedGoogle ScholarCrossref 135.van de Wal
M, Thewes
B, Gielissen
M, Speckens
A, Prins
J. Efficacy of blended cognitive behavior therapy for high fear of recurrence in breast, prostate, and colorectal cancer survivors: the SWORD study, a randomized controlled trial.
J Clin Oncol. 2017;35(19):2173-2183. doi:
10.1200/JCO.2016.70.5301PubMedGoogle ScholarCrossref 137.Hummel
SB, van Lankveld
JJDM, Oldenburg
HSA,
et al. Efficacy of internet-based cognitive behavioral therapy in improving sexual functioning of breast cancer survivors: results of a randomized controlled trial.
J Clin Oncol. 2017;35(12):1328-1340. doi:
10.1200/JCO.2016.69.6021PubMedGoogle ScholarCrossref 141.Dieng
M, Butow
PN, Costa
DS,
et al. Psychoeducational intervention to reduce fear of cancer recurrence in people at high risk of developing another primary melanoma: results of a randomized controlled trial.
J Clin Oncol. 2016;34(36):4405-4414. doi:
10.1200/JCO.2016.68.2278PubMedGoogle ScholarCrossref 142.Johannsen
M, O’Connor
M, O’Toole
MS, Jensen
AB, Højris
I, Zachariae
R. Efficacy of mindfulness-based cognitive therapy on late post-treatment pain in women treated for primary breast cancer: a randomized controlled trial.
J Clin Oncol. 2016;34(28):3390-3399. doi:
10.1200/JCO.2015.65.0770PubMedGoogle ScholarCrossref 143.Lengacher
CA, Reich
RR, Paterson
CL,
et al. Examination of broad symptom improvement resulting from mindfulness-based stress reduction in breast cancer survivors: a randomized controlled trial.
J Clin Oncol. 2016;34(24):2827-2834. doi:
10.1200/JCO.2015.65.7874PubMedGoogle ScholarCrossref 146.Nicolaije
KAH, Ezendam
NP, Vos
MC,
et al. Impact of an automatically generated cancer survivorship care plan on patient-reported outcomes in routine clinical practice: longitudinal outcomes of a pragmatic, cluster randomized trial.
J Clin Oncol. 2015;33(31):3550-3559. doi:
10.1200/JCO.2014.60.3399PubMedGoogle ScholarCrossref 147.van den Berg
SW, Gielissen
MF, Custers
JA, van der Graaf
WT, Ottevanger
PB, Prins
JB. BREATH: web-based self-management for psychological adjustment after primary breast cancer—results of a multicenter randomized controlled trial.
J Clin Oncol. 2015;33(25):2763-2771. doi:
10.1200/JCO.2013.54.9386PubMedGoogle ScholarCrossref 148.Epstein
RM, Duberstein
PR, Fenton
JJ,
et al. Effect of a patient-centered communication intervention on oncologist-patient communication, quality of life, and health care utilization in advanced cancer: the VOICE randomized clinical trial.
JAMA Oncol. 2017;3(1):92-100.
PubMedGoogle Scholar 149.Zick
SM, Sen
A, Wyatt
GK, Murphy
SL, Arnedt
JT, Harris
RE. Investigation of 2 types of self-administered acupressure for persistent cancer-related fatigue in breast cancer survivors: a randomized clinical trial.
JAMA Oncol. 2016;2(11):1470-1476. doi:
10.1001/jamaoncol.2016.1867PubMedGoogle ScholarCrossref 153.Mercieca-Bebber
R, King
MT, Calvert
MJ, Stockler
MR, Friedlander
M. The importance of patient-reported outcomes in clinical trials and strategies for future optimization.
Patient Relat Outcome Meas. 2018;9:353-367. doi:
10.2147/PROM.S156279PubMedGoogle ScholarCrossref 155.Davis
C, Naci
H, Gurpinar
E, Poplavska
E, Pinto
A, Aggarwal
A. Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13.
BMJ. 2017;359:j4530. doi:
10.1136/bmj.j4530PubMedGoogle ScholarCrossref