Atezolizumab plus chemotherapy feasible for NSCLC with brain metastases
medwireNews: Treatment with carboplatin and pemetrexed plus atezolizumab shows promise for people with nonsquamous non-small-cell lung cancer (NSCLC) and asymptomatic, untreated brain metastases, phase 2 study findings indicate.
The results of the ATEZO-BRAIN trial were presented at the IASLC 2021 World Conference on Lung Cancer by Ernest Nadal from the Institut Català d’Oncologia – L’Hospitalet in Barcelona, Spain.
He explained that people “with untreated brain metastases […] have been excluded or underrepresented in clinical trials evaluating chemotherapy plus immunotherapy in the first line setting.”
To address this, Nadal and team recruited 40 chemotherapy-naïve patients (median age 62.5 years, 72.5% men) with stage IV nonsquamous NSCLC without EGFR or ALK mutations and asymptomatic untreated brain metastases. Of these, 42.5% were receiving dexamethasone ≤4 mg/day at baseline.
The patients were given atezolizumab 1200 mg plus carboplatin (5 AUCs) and pemetrexed 500 mg/m2 every 3 weeks for four to six cycles, followed by pemetrexed plus atezolizumab maintenance until disease progression, unacceptable toxicity, or 2 years.
The study was permitted to continue after 12 weeks when the progression-free survival (PFS) rate was calculated to be at least 50% and the maximum rate of grade 3–4 toxicity was below 35%, as specified using historical data for chemotherapy alone, the presenter explained.
Nadal reported that, after a median 17.3 months of follow up, the intracranial objective response rate (ORR) was 40.0%, including four (10.0%) complete responses, while the systemic ORR was 47.4%, all of which were partial responses.
He added that just four patients had discordant central nervous system and systemic responses: two had stable disease in the brain and progressive disease in the body, and two had progressive disease in the brain and a partial response in the body.
The co-primary endpoint of PFS was a median 6.8 months for intracranial disease and 8.9 months for systemic disease, with corresponding 18-month PFS rates of 24.9% and 10.4%. Median overall survival was 13.6 months and 32.0% of participants were still alive at 2 years.
In terms of the second co-primary endpoint of safety, Nadal told delegates that the majority of treatment-related adverse events (TRAEs) were of grade 1 or 2 in severity. Grade 3 or 4 events were observed in 27.5% of patients and were most commonly anemia (20.0%), back pain (10.0%), and thrombocytopenia (5.0%). There were no grade 5 TRAEs but three patients (7.5%) experienced a grade 4 event (thrombocytopenia, neutropenia, and hallucinations).
Nadal concluded: “The safety profile and efficacy of atezolizumab combined with carboplatin and pemetrexed is favorable in patients with NSCLC and untreated brain metastases, including those receiving corticoids.”
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