Response to first-line chemotherapy regimen to predict efficacy of nivolumab in lung cancer.

Abstract

3026 Background: Nivolumab is a monoclonal antibody, targeting PD-1 receptor and demonstrating durable clinical benefit in 20% of metastatic NSCLC patients in second and further treatment lines. The expression of one of the PD-1 ligand, PD-L1 assessed by IHC is associated with better outcome. However, robust predictive markers of efficacy are lacking. Methods: 115 pts with stage IV NSCLC (42 squamous, 73 adenocarcinoma) were included in this retrospective study in 4 different institutions. They received nivolumab (3 mg/kg IV Q2W) after at least one line of systemic platinum-based chemotherapy. Response to first line chemotherapy and to nivolumab (RECIST 1.1) was determined on CT scan by two physicians. Association between best response to first-line regimen and PFS, OS or response to nivolumab was determined using both Chi2 and Cox analysis. Results: 46 (40%), 44 (38%) and 25 (22%) patients experimented PR, SD and PD to first-line platinum-based chemotherapy. 25 (22%), 34 (29.5%), 56 (48.5%) experimented PR, SD and PD to nivolumab. 59.5% (53/89) of patients who experimented clinical benefit (SD+PR) to first-line also experimented clinical benefit to nivolumab while only 20% (5/25) of patients with PD as best response to chemotherapy experimented clinical benefit to nivolumab (Chi2 test p = 0.002). The type of first-line doublet chemotherapy did not influence the response rate to nivolumab. Cox uni and multivariate models included age, histology and performance status underlined that patients with clinical benefit from chemotherapy had improved PFS with nivolumab (P = 0.002) (median PFS on nivolumab regimen of 4.9, 3.3 and 1.8 months for patients with PR, SD and PD to first-line, respectively). Similar results were obtained for OS (P = 0.03). Conclusions: Our data suggest that response to first-line chemotherapy may be a good surrogate marker of response, PFS and OS to post-platinum nivolumab in metastatic NSCLC.