ERBB gene mutations may affect the efficacy of therapies targeting the ERBB signaling pathway. Goss et al evaluated the association between the ERBB family of mutations and outcomes in afatinib- or erlotinib-treated patients with lung squamous cell carcinoma using samples from the LUX-Lung 8 trial. Of 245 evaluable patients, 53 had tumors with at least 1 ERBB mutation. Among afatinib-treated patients, progression-free and overall survival were longer in those with ERBB mutation–positive disease—in particular HER2 mutations—than in those without. HER2 mutations may be a biomarker for prioritizing afatinib treatment in this population. Gandara et al provide an Invited Commentary.
Invited Commentary
Joensuu et al report the results of the SOLD trial examining adjuvant trastuzumab treatment duration for HER2-positive breast cancer. Patients with HER2-positive, lymph node–positive (or node negative with large cancers), nonmetastatic breast cancer were randomized to chemotherapy consisting of 3 cycles of 3-weekly docetaxel plus trastuzumab for 9 weeks, followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide. After 9 weeks, trastuzumab was discontinued in arm 1, whereas arm 2 received trastuzumab to complete 1 year. Disease-free survival in the 9-week arm was not noninferior. This study suggests that chemotherapy and 1 year of trastuzumab therapy should remain standard of care.
Programmed cell death ligand 1 (PD-L1) protein expression and gene amplification has been associated with clinical response to immune checkpoint blockade for some cancers. To determine the prevalence of PD-L1 expression, Goodman et al analyzed 118 187 samples derived from the Foundation Medicine deidentified database. Overall, 0.7% of solid-tumor samples showed PD-L1 amplification, most often in breast or nasopharyngeal carcinoma, lung or head and neck squamous cell carcinoma, soft-tissue sarcoma, thyroid anaplastic carcinoma, and kidney sarcomatoid carcinoma. These data confirm that PD-L1 gene amplification occurs only in a small subset of solid tumors.
When patients with acute myeloid leukemia (AML) experience relapse after allogeneic transplant, what is the optimal treatment: donor lymphocyte infusion or a second allogeneic transplant? In a cohort study from the European Society for Blood and Marrow Transplantation, Kharfan-Dabaja et al evaluated clinical outcomes in 418 adults with AML who relapsed after initial allogeneic transplant. There was no difference in overall survival at 2 or 5 years between the 137 individuals who received a second allogeneic transplant and the 281 who received donor lymphocyte infusion. Overall survival was optimal when either treatment was given during complete remission.
NRG Oncology RTOG 0618 tested stereotactic body radiation therapy (SBRT) in treating patients with operable early-stage lung cancer. Timmerman et al report the long-term results of the use of SBRT rather than surgery in 26 patients. The SBRT dose was 54 Gy delivered in three 18-Gy fractions over 1.5 to 2 weeks. The 4-year estimates of disease-free and overall survival were 57% and 56%, respectively. Only 2 patients had grade 3 adverse events. The authors conclude that SBRT seems to be associated with a high rate of primary tumor control and low treatment-related morbidity.
Related Article