Atezolizumab with or without bevacizumab and platinum-pemetrexed in patients with stage IIIB/IV non-squamous non-small cell lung cancer with EGFR mutation, ALK rearrangement or ROS1 fusion progressing after targeted therapies: a multicenter phase II open-label non-randomized study GFPC 06-2018
Mené en France sur 149 patients atteints d'un cancer du poumon non à petites cellules non épidermoïde de stade IIIB/IV présentant des mutations du gène EGFR ou des réarrangements des gènes ROS1 ou ALK, cet essai multicentrique non randomisé évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité d'un traitement combinant atézolizumab et chimiothérapie à base de pémétrexed et sels de platine, avec ou sans bévacizumab, après l'échec de thérapies ciblées
Background: Previous reports showed limited efficacy of immune checkpoint inhibitors (ICI) as single agent treatment for non-small cell lung cancer (NSCLC) with EGFR mutation or ALK/ROS1 fusion. We aimed at evaluating the efficacy and safety of ICI combined with chemotherapy and bevacizumab (when eligible) in this patient subgroup. Methods: We conducted a French national open-label multicenter non-randomized non-comparative phase II study in patients with stage IIIB/IV NSCLC, oncogenic addiction (EGFR mutation or ALK/ROS1 fusion), with disease progression after tyrosine-kinase inhibitor and no prior chemotherapy. Patients received platinum-pemetrexed-atezolizumab-bevacizumab (PPAB cohort) or, if not eligible to bevacizumab, platinum-pemetrexed-atezolizumab (PPA cohort). The primary endpoint was the objective response rate (ORR; RECIST v1.1) after 12 weeks, evaluated by blind independent central review. Results: 71 patients were included in PPAB cohort and 78 in PPA cohort (mean age, 60.4/66.1 years; women 69.0%/51.3%; EGFR mutation, 87.3%/89.7%; ALK rearrangement, 12.7%/5.1%; ROS1 fusion, 0%/6.4%, respectively). After 12 weeks, ORR was 58.2% (90%CI, 47.4–68.4) in PPAB cohort and 46.5% (90%CI, 36.3-56.9) in PPA cohort. Median PFS and OS were 7.3 (95%CI 6.9-9.0) months and 17.2 (95%CI 13.7-NA) months in PPAB cohort and 7.2 (95%CI 5.7-9.2) months and 16.8 (95%CI 13.5-NA) months in PPA cohort, respectively. Grade 3-4 adverse events (AEs) occurred in 69.1% of patients in PPAB cohort and 51.4% in PPA cohort; Grade 3-4 atezolizumab-related AEs occurred in 27.9% and 15.3%, respectively. Conclusion: Combination approach with atezolizumab with or without bevacizumab and platinum-pemetrexed achieved promising activity in metastatic EGFR-mutated or ALK/ROS1-rearranged NSCLC after TKI failure, with acceptable safety profile.