Background Remarkable breakthroughs in immune checkpoint inhibitors (ICIs) for treating driverless target lung cancers have resulted in significant patient survival benefits. However, the efficacy of this approach in lung cancer patients with HER2 mutation remains debatable.
Methods Through retrospective analysis of pooled data from two large randomized trials, Phase II POPLAR (NCT01903993) and Phase III OAK (NCT02008227), we identified 1137 cases of previously treated non-small cell lung cancer (NSCLC) with sufficient blood specimens for bTMB testing who randomly assigned to receive atezolizumab (n =429) or docetaxel (n =708). The primary objective of this analysis was to assess the efficacy of immunotherapy in HER2-positive patients.
Results A total of 35 of all patients were HER2 positive (35/1137, 3.07%). Of these patients receiving immunotherapy (n=11) and chemotherapy (n=24), mPFS was 4.21 and 5.17 months, respectively [hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.25–1.3]. No significant correlation between HER2 positivity and the efficacy of chemotherapy and immunotherapy. Multivariate analysis also showed no significant correlation between HER2 positivity and PFS or OS in all patients receiving immunotherapy (n=429). The mPFS for HER2-positive (n=10) versus HER2-negative (n=419) patients was 2.84m, 2.73m (HR 0.89, 95% CI 0.44–1.8) and mOS was 15.5m, 12.6m (HR 0.68, 95% CI 0.28–1.65). In addition, bTMB-high had a longer mOS compared to bTMB-low in both the allimmunotherapy population and HER2-positive patients (13.24 vs. 9.49 months, P < 0.05; 11.14 vs. 6.49 months, P < 0.05). The bTMB is a predictive biomarker for OS in atezolizumab-treated NSCLC patients compared to docetaxel-treated patients (bTMB-high: HR Ate vs. Dtx = 1.47 [95% CI: 0.60–3.58], P = 0.401; bTMB-low: HR Ate vs. Dtx = 0.56 [95% CI: 0.20–1.59], P = 0.279).
Conclusions Regardless of docetaxel and atezolizumab in second-line were less effective in HER2-positive NSCLC patients. However, bTMB is a potential biomarker for immunotherapy in HER2-positive NSCLC.
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