Combination of chemotherapy and immune checkpoint inhibitors shows promise in NSCLC patients with untreated brain metastases

Reviewed by Emily Henderson, B.Sc.Sep 12 2021

Treatment with atezolizumab plus carboplatin and pemetrexed was safe and yielded promising brain progression-free survival in patients with nonsquamous non-small cell lung cancer with untreated and asymptomatic brain metastases. The study was presented today at the IASLC 2021 World Conference on Lung Cancer.

According to Ernest Nadal, MD, of the Catalan Institute of Oncology/IDIBELL, L'Hospitalet, Barcelona, Spain, patients with untreated brain metastases have been excluded or underrepresented in clinical trials conducted in the first line setting evaluating the combination of chemotherapy plus immune checkpoint inhibitors.

To determine the safety and efficacy of chemotherapy plus atezolizumab in patients with NSCLC with asymptomatic untreated brain metastases, Dr. Nadal and his co-researchers at 11 clinical sites enrolled 40 patients with stage IV non-squamous NSLC without EGFR or ALK genetic alterations with untreated brain metastases. All enrolled patients had not been previously treated with chemotherapy.

Patients received carboplatin and pemetrexed plus atezolizumab every 3 weeks for four to six cycles, followed by maintenance with pemetrexed plus atezolizumab until progressive disease or a maximum of 2 years. Co-primary endpoints were safety and investigator-assessed progression-free survival at 12 weeks.

At 12 weeks, 16 (40%) patients had a response and 19 (47.5%) had stable disease in the central nervous system, while 19 (47.5%) had a systemic response. Only four patients had discordance between their central nervous system and systemic responses (two with partial disease in the brain and a partial response in the body, and two with stable disease in the brain and partial disease in the body).

At 12 weeks, the overall progression-free survival rate was 60% and grade 3-4 toxicity was 27.5%. Intracranial and systemic progression-free survival were 6.9 months (95% CI 4.7-12.1) and 8.9 months, (95% CI 6.7- 13.8), respectively. Treatment was well tolerated, and no grade five toxicities were observed. Treatment-related adverse events grade 3 in 5% or greater of patients included anemia (8 patients), back pain (4 patients), thrombocytopenia (two patients) and dyspnea, pneumonitis and ALT (1 patient each). Three patients had grade 4 treatment-related adverse events consisting of thrombocytopenia, neutropenia, and hallucinations.

Treatment with atezolizumab plus carboplatin and pemetrexed was safe and yielded promising brain progression-free survival in patients with nonsquamous NSCLC with untreated and asymptomatic brain metastases."

Dr. Ernest Nadal, MD, Catalan Institute of Oncology/IDIBELL, L'Hospitalet, Barcelona, Spain