The following is a summary of “Phase II Trial of Atezolizumab Combined With Carboplatin and Pemetrexed for Patients With Advanced Nonsquamous Non–Small-Cell Lung Cancer With Untreated Brain Metastases,” published in the October 2023 issue of Oncology by Nadal, et al.
For an Atezo-Brain study, researchers sought to assess the effectiveness of atezolizumab in combination with chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC) who had untreated brain metastases, a group typically excluded from clinical trials.
The single-arm phase II clinical trial enrolled patients with advanced nonsquamous NSCLC who had untreated brain metastases but did not show neurological or manageable symptoms with medical treatment. Dexamethasone, a corticosteroid, was allowed up to a maximum daily dose of 4 mg. The treatment regimen involved administering atezolizumab in combination with carboplatin and pemetrexed for four to six cycles, followed by continued treatment with atezolizumab and pemetrexed until disease progression or a maximum duration of 2 years. The primary endpoints of the study were to determine the progression-free survival (PFS) rate at 12 weeks and the incidence of severe (grade ≥3) adverse events during the first 9 weeks. Intracranial outcomes were assessed using response assessment criteria specific to brain metastases in neuro-oncology.
Forty patients were enrolled in the study, with 22 of them (55%) already receiving corticosteroids at the beginning of the trial. The overall 12-week PFS rate was 62.2% (with a 95% credibility interval ranging from 47.1 to 76.2). The rate of severe (grade 3/4) adverse events during the initial 9 weeks of treatment was 27.5%. While most neurologic events were of grade 1 or 2 severity, five patients (12.5%) experienced severe (grade 3-4) neurologic events. With a median follow-up duration of 31 months, the median PFS for intracranial disease was 6.9 months, with a response rate of 42.7% (95% CI, 28.1 to 57.9). Systemic median PFS was 8.9 months, with a response rate of 45% (95% CI, 28.1 to 57.9). The median overall survival (OS) was 11.8 months (95% CI, 7.6 to 16.9), and the 2-year OS rate was 27.5% (95% CI, 16.6 to 45.5).
Atezolizumab, in combination with carboplatin and pemetrexed, demonstrated efficacy in patients with advanced nonsquamous NSCLC who have untreated brain metastases, with an acceptable safety profile.