Updated analysis from the ATEZO-BRAIN trial: Atezolizumab plus carboplatin and pemetrexed in patients with advanced nonsquamous non–small cell lung cancer with untreated brain metastases.
Ernest Nadal, Delvys Rodríguez‐Abreu, Bartomeu Massutí, Oscar Juan-Vidal, Gerardo Huidobro Vence, Rafael López‐López, Javier de Castro, Anna Estival, Rosario García Campelo, Ivana Sullivan, Enriqueta Felip, Ana Blasco, M. Guirado, Noelia Vilariño, Marta Simó, Marta Sanahuja, Anna Hernández‐Aguilera, Valentín Navarro, Jordi Bruna
Abstract
9010 Background: Atezolizumab plus chemotherapy was safe and yielded promising clinical outcome as frontline therapy for patients (pts) with advanced NSCLC with untreated brain metastases (BM) in the ATEZO-BRAIN study (NCT03526900). Methods: A multicenter single-arm phase II trial with a Bayesian design for evaluating the safety and efficacy of atezolizumab plus carboplatin with pemetrexed every 3 weeks for 4-6 cycles, followed by maintenance with pemetrexed plus atezolizumab in pts with stage IV non-squamous NSCLC without EGFR or ALK genetic alterations and untreated BM. Pts not presented neurologic symptoms at baseline; but anticonvulsants and dexamethasone (DXM) ≤ 4mg qd were allowed. Co-primary endpoints were safety and investigator-assessed progression-free survival (PFS) at 12 weeks according to RANO-BM and RECIST v1.1 for brain and systemic disease, respectively. Here we present the final data and an exploratory analysis based on PD-L1 expression and corticosteroid treatment at baseline. Results: Out of 40 pts included in the study, 22 (55%) were receiving DXM at baseline and 20 (50%) had positive expression of PD-L1. Sixteen (40%) pts had confirmed intracranial response based on RANO-BM (12 PR, 4 CR) and 19 (47.5%) pts achieved systemic response (all PR). Only 4 pts had discordant responses between the body and the brain. No differences were observed in the overall systemic and intracranial response rate according to the PD-L1 expression or the use of corticosteroids at baseline. As of December 31, 2021 (median follow-up, 20 months), the updated median (95% CI) systemic PFS was 8.9 (6.7 to 13.8) and intracranial PFS was 6.9 (4.7 to 11.9). Median (95% CI) OS was 13.6 (9.72 to not reached) and estimated 2-year OS rate (95% CI) was 30.5% (18.4 to 50.4). Median (95%CI) OS was longer for PD-L1 positive pts (16.2; 10.3 to not reached) compared to PD-L1 negative pts (10.7; 7.6 to not reached) but differences were not statistically significant due to the limited statistical power (HR = 0.99; 95% CI 0.35 to 2.12). No significant differences in OS were observed between pts receiving or not baseline DXM treatment. Treatment was well tolerated and no grade 5 toxicities were observed. Conclusions: In this updated analysis, treatment with atezolizumab plus carboplatin and pemetrexed yields a promising 2-year OS rate and intracranial response rate in patients with untreated BM from NSCLC, regardless of treatment with corticosteroids at baseline and PD-L1 expression. Clinical trial information: NCT03526900.