Maintenance Bevacizumab, Pemetrexed, or Both in Advanced Nonsquamous NSCLC
In the phase III ECOG-ACRIN 5508 trial, reported in the Journal of Clinical Oncology by Ramalingam et al, maintenance pemetrexed or bevacizumab was associated with no significant improvement in overall survival vs the bevacizumab control group alone, and was associated with greater toxicity in patients with advanced nonsquamous non–small cell lung cancer (NSCLC).
Study Details
The multicenter trial enrolled 1,516 patients with no prior treatment for advanced disease between August 2010 and April 2015. Patients received carboplatin (AUC 6), paclitaxel (200 mg/m2), and bevacizumab (15 mg/kg) every 3 weeks for up to four cycles. Patients without progression after four cycles of induction were randomly assigned to receive maintenance therapy with bevacizumab (15 mg/kg), pemetrexed (500 mg/m2), or the combination every 3 weeks, with treatment continued until disease progression, unacceptable toxicity, or withdrawal of consent.
A total of 874 patients were randomly assigned to the bevacizumab group (n = 287), the pemetrexed group (n = 294), or the combination group (n = 293). Results were released to the study team in October 2018 after full data maturity had been reached. The primary endpoint was overall survival, with the bevacizumab group serving as the control group.
Survival and Adverse Events
Median follow-up was 50.6 months. Median overall survival was 14.4 months in the bevacizumab group vs 15.9 months in the pemetrexed group (hazard ratio [HR] = 0.86, P = .12) and 16.4 months in the combination group (HR = 0.9, P = .28). Median progression-free survival was 4.2 months in the bevacizumab group vs 5.1 months in the pemetrexed group (HR = 0.85, P = .06) and 7.5 months in the combination group (HR = 0.67, P < .001).
Grade ≥ 3 adverse events occurred in 30% of the bevacizumab group, 38% of the pemetrexed group, and 51% of the combination group (P < .001 vs bevacizumab). Compared with the bevacizumab group, the pemetrexed group had a higher incidence of grade 3 or 4 anemia, fatigue, lymphopenia, neutropenia, thrombocytopenia, and leukopenia, whereas the bevacizumab group had a higher incidence of grade 3 or 4 proteinuria and hypertension vs the pemetrexed group. The combination group had a higher incidence of anemia, fatigue, lymphopenia, neutropenia, thrombocytopenia, and leukopenia vs the bevacizumab group.
The investigators concluded, “Single-agent bevacizumab or pemetrexed is efficacious as maintenance therapy for advanced nonsquamous NSCLC. Because of a lack of survival benefit and higher toxicity, the combination of bevacizumab and pemetrexed cannot be recommended.”
Suresh S. Ramalingam, MD, of Winship Cancer Institute, Emory University School of Medicine, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit jco.ascopubs.org.
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