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.

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.

Intracranial activity of first-line immune checkpoint inhibitors combined with chemotherapy in advanced non-small cell lung cancer

“…[15,23,24] Interestingly, in the Atezo-Brain study, patients with PD-L1-positive NSCLCs exhibited a trend of better OS with first-line atezolizumab plus chemotherapy than those with PD-L1negative status; however, the difference was not statistically significant due to limited statistical power. [18] In terms of treatment safety, the overall AE rate in the ICI + chemo group was 55.9%, with a 11.8% grade 3- 4 AE rate. No new or unexpected safety signals were observed, and all AEs in both groups were manageable.…”

Safety and efficacy of immune checkpoint blockade in patients with advanced nonsmall cell lung cancer and brain metastasis

“…The 18‐month systemic PFS rate reached 24.9% in comparison with 10.4% intracranially. Finally, the median OS (mOS) was 13.6 months (95% CI, 9.72‐not reached) and 30.5% (95% CI, 18.4%‐50.4%) of the participants were alive at 2 years 70,71 …”

“…80 According to the updated analysis from the atezo-brain trial, no grade 5 trAEs occurred and the combination treatment with atezolizumab plus chemotherapy was well tolerated. 71 It is also worth noting that approximately 96% of patients in the BM subgroup, who received the atezolizumab-based quadruplet in the Impower150 trial, experienced at least one irAE regardless of the received treatment.…”

Chemoimmunotherapy for Untreated Lung Cancer Brain Metastases: Systemic Before Local Therapy?

“…In the article that accompanies this editorial, Nadal et al 8 present the results of a single-arm, multicenter phase II study (Atezo-Brain) investigating the safety and efficacy of atezolizumab in combination with carboplatin and pemetrexed in patients with advanced, nonsquamous non–small-cell lung cancer with clinically stable, untreated brain metastases. In addition to demonstrating the intracranial safety and efficacy of chemoimmunotherapy, even in patients with a considerable burden of intracranial disease, the results from this study suggest that the use of systemic therapy before local therapy allows for the delay of whole-brain radiation therapy while preserving the quality of life and function of patients with clinically stable brain metastases.…”

“…In the article that accompanies this editorial, Nadal et al 8 add to the limited body of literature a report of the safety and efficacy of the anti–PD-L1-targeting immune checkpoint inhibitor, atezolizumab, combined with carboplatin and pemetrexed in a single-arm, multicenter phase II clinical trial that included 40 patients with advanced, nonsquamous NSCLC and untreated, clinically stable brain metastases. Notably, the study required at least one brain metastasis measuring 10 mm or greater, there was no upper limit on intracranial disease burden, and patients on corticosteroids (equivalent to a total daily dose of dexamethasone ≤ 4 mg) were included.…”