According to researchers, 3 to 5% of patients with mNSCLC have ERBB2 (HER2) mutations. However, no targeted treatments are approved by the FDA for this population. To evaluate the efficacy of trastuzumab in ERBB2-mutant mNSCLC, we compared it to non-targeted treatments. Patients with mNSCLC who had ERBB2 changes detected by next-generation sequencing were included in this retrospective, single-institution analysis. The response evaluation criteria in solid tumors (RECT) 1.1 criteria were used to find the best overall answer. Investigators found 3 groups of patients: ERBB2-mutant/EGFR-wildtype mNSCLC (n=33), ERBB2-amplified/EGFR-wildtype mNSCLC without ERBB2 mutations (n=6), and ERBB2-altered/EGFR-mutant mNSCLC (n=8). There were 23 cases of A775_G776insYVMA, 4 cases of Gly778_Pro780dup, 3 cases of Ser310Phe, and 5 cases of other mutations. The median overall survival (OS) for the 33 people with ERBB2-mutant/EGFR-wildtype mNSCLC was 17.7 months for those with A775_G776insYVMA and 52.9 months for those without it (Cox regression multivariable HR:5.03, 95% CI:1.37-18.51, P=.02). This is a big difference. Trastuzumab-based therapies were linked to longer overall survival for people with mNSCLC with A775_G776insYVMA (20.3 vs. 9.8 months; multivariable HR:0.19, 95% CI:0.04-0.87, P=.032). For the 33 patients with ERBB2-mutant/EGFR-wildtype mNSCLC, the objective response rate and disease control rate (median tumor size change) were 40.0% and 80.0% (-35.8%), respectively, for patients treated with trastuzumab deruxtecan; 0% and 30.0% (-5.2%) for trastuzumab emtansine; and 7.1% and 50.0% (-13.0%) for trastuzumab/chemotherapy combinations. Most trastuzumab-based regimens in this real-world investigation showed very modest effectiveness against ERBB2-mutant/EGFR-wildtype mNSCLC; however, trastuzumab deruxtecan had the highest response rates and best tumor size reduction. Those with A775_G776insYVMA who received any trastuzumab-based therapy had longer overall survival. For patients with ERBB2-mutant/EGFR-wildtype NSCLC, there is still a need for FDA-approved targeted treatments.

Source:lungs cancer sciencedirect.com/science/article/abs/pii/S1525730422001280