What are the real-world survival outcomes associated with use of pertuzumab and trastuzumab emtansine (T-DM1) for ERBB2-positive metastatic breast cancer?
In this cohort study of 795 women in Ontario, Canada, median survival with pertuzumab (43 months) and T-DM1 (15 months) were substantially shorter than outcomes reported in previous pivotal trials. The reduced survival in the pertuzumab group may be explained by the older age of patients in routine practice; among the T-DM1 cohort, median survival was shorter for patients with prior receipt of pertuzumab than in the pertuzumab-naive subgroup.
Median survival in the real-world appears inferior to results of pivotal trials, and differences in outcome likely reflect differences in patient population and previous lines of therapy in routine practice.
Clinical trials have shown that the addition of pertuzumab to trastuzumab-based chemotherapy for first-line treatment of ERBB2-positive metastatic breast cancer is associated with considerable improvement in overall survival (OS). In the second-line setting, trastuzumab emtansine (T-DM1) improves OS compared with capecitabine/lapatinib in patients previously treated with trastuzumab-based chemotherapy. However, there are few data describing long-term real-world outcomes with these agents.
To describe practice patterns and outcomes associated with pertuzumab and T-DM1 in routine clinical practice.
Design, Setting, and Participants
This population-based retrospective cohort study used the Ontario Cancer Registry linked to electronic treatment databases to identify all patients treated with pertuzumab and T-DM1 following reimbursement approval in Ontario, Canada, which has a single-payer public health system. Participants included women with stage IV ERBB2-positive metastatic breast cancer receiving treatment with pertuzumab for first-line metastatic indication from December 2013 through December 2017, and those treated with T-DM1 from May 2014 through December 2017. Pertuzumab and T-DM1 cohorts were analyzed separately. Data were analyzed December 2019 to December 2020.
Treatment with pertuzumab or T-DM1.
Main Outcomes and Measures
The primary outcome was OS, determined using the Kaplan-Meier method. Factors associated with OS were identified using a Cox proportional hazard model.
The median (interquartile range [IQR]) age of the 795 women who received pertuzumab and 506 women who received T-DM1 was 57 (49-67) and 56 (48-66) years, respectively. Among the entire population, the median (IQR) OS and time on treatment was 43 (16.2-unavailable) and 14 (6.0-26.2) months, respectively. In the T-DM1 cohort, the proportion of pertuzumab-naive patients decreased over time from 68 of 91 [74.7%] in 2014 to 16 of 89 [18.0%] in 2017 (P < .001). The median (IQR) OS and time on treatment was 15 (6.7-27.7) and 4 (1.4-9.0) months, respectively. Median OS was shorter for patients with prior pertuzumab treatment than in the pertuzumab-naive subgroup (12 vs 19 months; adjusted hazard ratio, 0.70; 95% CI, 0.55-0.89; P = .004).
Conclusions and Relevance
In this population-based cohort study, the survival of patients treated with pertuzumab and T-DM1 in routine practice appeared inferior to results from pivotal clinical trials. Differences in outcome likely reflect differences in patient population and previous lines of therapy in routine practice. Further work is needed to understand the effectiveness of T-DM1 after pertuzumab exposure.
Identify all potential conflicts of interest that might be relevant to your comment.
Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.
Err on the side of full disclosure.
If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.
Not all submitted comments are published. Please see our commenting policy for details.
Ethier J, Desautels D, Robinson A, Amir E, Kong W, Booth CM. Practice Patterns and Outcomes of Novel Targeted Agents for the Treatment of ERBB2-Positive Metastatic Breast Cancer. JAMA Oncol. Published online July 08, 2021. doi:10.1001/jamaoncol.2021.2140
Customize your JAMA Network experience by selecting one or more topics from the list below.
Create a personal account or sign in to: