Atezolizumab promising for treating NSCLC brain metastases

In treatment-naïve subjects with non-squamous non-small-cell lung cancer (NSCLC) and asymptomatic brain metastases, immune checkpoint inhibitor atezolizumab in combination with carboplatin plus pemetrexed prolonged progression-free survival (PFS) in a phase 2 trial [1].

Patients with brain metastases are often excluded from clinical trials; yet, the prognosis for people with brain metastases is very poor. Prof. Ernest Nadal (Catalan Institute of Oncology, Spain) presented the multicentre, non-randomised, phase 2 ATEZO-BRAIN trial (NCT03526900), which was designed to evaluate the efficacy of atezolizumab with respect to PFS rate in patients with NSCLC with asymptomatic brain metastasis. ATEZO-BRAIN recruited 40 such patients, excluding any patients with EGFR mutations or ALK fusions. Baseline use of corticosteroids was permitted. Patients completed 4 to 6 cycles of carboplatin (AUC5 on day 1 of each 3-week cycle) plus pemetrexed (500 mg/m2 intravenously on day 1 of each 3-week cycle) and atezolizumab (1,200 mg intravenously on day 1 of each 3-week cycle), then continued maintenance pemetrexed and atezolizumab until either unacceptable toxicity was reached, their disease progressed, or they completed 2 years of therapy. In addition, folic acid, vitamin B12, and dexamethasone 4 mg twice daily was administered one day before and after pemetrexed treatment.

Co-primary endpoints were safety, and investigator-based PFS according to Response Assessment in Neuro-Oncology (RANO) and Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 criteria for brain and systemic disease respectively.

Following a median of 4 cycles of carboplatin and 8.5 cycles of pemetrexed and atezolizumab, the primary rate of PFS at 12 weeks was 60%. Fatigue and anaemia were the most frequently reported adverse events. Most treatment-related adverse events were grade 1 or 2; the grade 3–4 toxicity rate was 27.5%. There were no fatal adverse events.

After a median follow-up period of 17.3 months, the median systemic PFS was 8.9 months, with an 18-month PFS rate of 24.9%. The median intracranial PFS was 6.9 months, with an 18-month PFS rate of 10.4%. The 2-year overall survival rate was 32%.

The investigators concluded that the safety profile and efficacy of atezolizumab combined with carboplatin and pemetrexed is favourable for patients who have NSCLC and untreated brain metastases.

1. Nadal E. Atezo-Brain: Single arm phase 2 study of atezolizumab plus chemotherapy in stage 4 NSCLC with untreated brain metastases. OA 09.02, WCLC 2021, 8–14 September.

 

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Posted on 21 September, 202115 February, 2024