1016P GFPC 06-2018: A multicentre phase II, open-label, non-randomized study evaluating platinum-pemetrexed-atezolizumab (+/- bevacizumab) for patients with stage IIIB/IV non-squamous NSCLC with EGFR mutation, ALK rearrangement or ROS1 fusion progressing after targeted therapies

Abstract

For patients (pts) with stage IIIB/IV NSCLC without oncogenic addiction (OA), immuno-checkpoint inhibitors (ICI) have emerged as a standard first-line treatment. Literature suggests a lower efficacy of ICI as single treatment in pts with OA, notably EGFR mutation or ALK/ROS1 rearrangement. Assuming adding chemotherapy to immunotherapy (CT-IO) may improve the management of pts with OA, we implemented a trial to assess the efficacy of this combination in this setting. We conducted a national, open, multicentre, non-randomized Phase II Study with two parallel cohorts: A (Platinum-Pemetrexed-Atezolizumab-Bevacizumab) and B (Platinum-Pemetrexed-Atezolizumab). Main eligibility criteria were: stage IIIB/IV NSCLC with EGFR mutation or ALK/ROS1 rearrangement progression after ≥1 targeted therapy and no prior chemotherapy and eligible for Bevacizumab (A). The primary endpoint was objective response rate (ORR) after 4 cycles (RECIST 1.1) evaluated by masked, independent central review. The secondary endpoints were PFS, OS and safety profile. For cohort A, an ORR of 35% (p0) was undesirable (and p1=50% expected). For cohort B, p0=30% and p1=45%. 149 pts were included (71 in A, 78 in B): for A/B respectively, mean age, 60.4/66.1 years; men 31/49%; alteration for EGFR 87/90%, ALK 13/5%, ROS1 0/6%. ORR was 58.2% (90% CI 47.4-68.4%, p<0.01) in A and 46.5% (90% CI 36.3-56.8%, p<0.01) in B. Disease control rate at 12 weeks was 89.6% (A) and 81.7% (B). Median PFS and OS were respectively 7.3 months (95% CI 6.9- 9.0), 17.2 months (95% CI 13.7-NA) in A and 7.2 months (95% CI 5.7-9.2), 16.8 months (95% CI 13.5-NA) in B. Grade 3-4 adverse events (AE) occurred in 69.1/51.4% (A/B). Severe immune-related AE occurred in 27.9/15.3% (A/B). No toxicity-related death was observed. Combination approach of Platinum-Pemetrexed-Atezolizumab-Bevacizumab or Platinum-Pemetrexed-Atezolizumab achieved promising efficacy in metastatic EGFR/ALK mutated NSCLC after TKI failure, with acceptable tolerance profile.