In a Spanish phase II study (Atezo-Brain; GECP17/05) reported in the Journal of Clinical Oncology, Ernest Nadal, MD, PhD, and colleagues investigated the activity of the combination of atezolizumab with chemotherapy in patients with advanced nonsquamous non–small cell lung cancer (NSCLC) with untreated brain metastases.
Study Details
Forty patients with untreated brain metastases who had no neurologic symptoms or were asymptomatic with medical treatment were enrolled in the multicenter trial between November 2018 and December 2019. Treatment consisted of atezolizumab at 1,200 mg every 3 weeks with carboplatin area under the curve = 5 and pemetrexed at 500 mg/m2; after four to six cycles, patients received atezolizumab and pemetrexed maintenance therapy until disease progression or for up to 2 years. Dexamethasone at up to 4 mg once daily was permitted. A total of 22 patients (55%) were receiving corticosteroids at baseline. The primary endpoints were overall progression-free survival at 12 weeks and incidence of grade ≥ 3 adverse events during the first 9 weeks of treatment.
Ernest Nadal, MD, PhD
Key Findings
The overall 12-week progression-free survival rate was 62.2% (95% credibility interval [CrI] = 47.1%–76.2%).
The rate of grade 3 or 4 adverse events (no grade 5 events) during the first 9 weeks of treatment was 27.5%, including grade 3 or 4 neurologic events in five patients (12.5%). Most neurologic adverse events were grade 1 or 2.
Intracranial response was observed in 17 patients (42.7%, 95% CrI = 28.1%–57.9%), including complete response in 5. Median duration of intracranial response was 14 months (95% confidence interval [CI] = 10 months to not reached). Systemic response was observed in 18 patients (45%, 95% CrI = 28.1%–57.9%), with complete response in 1. Median duration of systemic response was 11.9 months (95% CI = 8.9 months to not reached).
At a minimum follow-up of 27 months, median intracranial progression-free survival was 6.9 months (95% CI = 4.7–11.9 months) and median systemic progression-free survival was 8.9 months (95% CI = 6.7–13.8 months). Median overall survival was 11.8 months (95% CI = 7.6–16.9 months), with 1- and 2-year rates of 50% (95% CI = 36.7%–68.2%) and 27.5% (95% CI = 16.6%–45.5%).
The investigators concluded, “Atezolizumab plus carboplatin and pemetrexed demonstrates activity in patients with advanced nonsquamous NSCLC with untreated brain metastases with an acceptable safety profile.”
Dr. Nadal, of the Department of Medical Oncology, Catalan Institute of Oncology, L’Hospitalet de Llobregat, Barcelona, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Roche. For full disclosures of the study authors, visit ascopubs.org.
