KEY TAKEAWAYS
- ATEZO-BRAIN is a phase 2 clinical trial (NCT03526900) to assess the efficacy of atezolizumab + chemotherapy for patients with advanced NSCLC and untreated BM.
- Patients with NSCLC are administered atezolizumab + carboplatin with pemetrexed every three weeks for 4-6 cycles, followed by maintenance with pemetrexed + atezolizumab and evaluated in this randomized, single-arm, multicenter study.
- Researchers used RANO-BM or RECIST v1.1 criteria to measure PFS and OS rates at 12 weeks and two years.
- The study exhibited that Atezolizumab Plus Carboplatin & Pemetrexed resulted in 40% cerebral response, 47.5% systemic response, and a 30.5% 2-year OS rate.
In the ATEZO-BRAIN research, patients with advanced NSCLC with untreated brain metastases (BM) experienced a safe and favorable clinical outcome when treated with atezolizumab plus chemotherapy as frontline therapy (NCT03526900).
Patients with stage IV non-squamous NSCLC without EGFR or ALK genetic alterations and untreated BM were chosen for a randomized, single-arm, multicenter phase II trial study of the efficacy of atezolizumab + carboplatin with pemetrexed every three weeks for 4-6 cycles, followed by maintenance with pemetrexed + atezolizumab. Anticonvulsants and dexamethasone (DXM) ≤ 4mg qd were permitted for patients who did not display neurologic symptoms at baseline. The investigator-assessed progression-free survival (PFS) at 12 weeks using the RANO-BM or RECIST v1.1 criteria for brain or systemic disease were co-primary objectives. The final results and an exploratory analysis based on PD-L1 expression and pre-treatment with corticosteroids are shown in this study.
Twenty-two patients (55%) were receiving DXM at baseline, while twenty patients (50%) showed positive expression of PD-L1. The RANO-BM confirmed cerebral response in 16 patients (40%) (12 PR, 4 CR), while the systemic response was reached in 19 patients (47.5%). (all PR). Only four pts showed inconsistent physical and mental reactions. There was no correlation between baseline PD-L1 expression or corticosteroid use and systemic and intracranial response rate. The updated median (95% CI) systemic PFS was 8.9 (6.7 to 13.8), and intracranial PFS was 6.9 (5.0 to 14.0) as of December 31, 2021 (median follow-up, 20 months) (4.7 to 11.9). The median OS (95% CI) was 13.6 (9.72 to not reached) (18.4 to 50.4), and the expected two-year OS rate (95% CI) was 30.5%. Although PD-L1 positive patients had a longer median (95%CI) OS (16.2; 10.3 to not reached) than PD-L1 negative patients (10.7; 7.6 to not reached), this difference was not significant statistically (HR = 0.99; 95% CI 0.35 to 2.12). No statistically significant variations in OS existed between patients with baseline DXM therapy and those without. No major negative events were associated with the treatment, and the patients tolerated it well.
Patients with untreated BM from NSCLC have a promising 2-year OS rate and intracranial response rate when treated with atezolizumab plus carboplatin and pemetrexed, regardless of baseline corticosteroid treatment and PD-L1 expression, as shown in this revised analysis.
Source: https://meetings.asco.org/abstracts-presentations/209471
Clinical trial: https://clinicaltrials.gov/ct2/show/NCT03526900
Nadal, E., Rodriguez-Abreu, D., Massuti, B., Juan-Vidal, O., Huidobro Vence, G., Lopez, R., de Castro Carpeño, J., Estival, A., Campelo, R. G., Sullivan, I., Felip, E., Blasco, A., Guirado, M., Vilarino, N., Simo, M., Sanahuja, M., Hernandez, A., Navarro, V., & Bruna, J. (2022). 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. Journal of Clinical Oncology, 40(16_suppl), 9010–9010. https://doi.org/10.1200/jco.2022.40.16_suppl.9010
