As reported in The Lancet Oncology by Baize et al, a French phase III trial has shown significant improvement in progression-free survival with second-line carboplatin plus etoposide vs topotecan in patients with chemotherapy-sensitive relapsed small cell lung cancer.
As noted by the investigators, topotecan is currently the only drug approved in Europe for second-line treatment of small cell lung cancer.
The open-label multicenter trial enrolled patients with advanced or locally relapsed disease who had responded to first-line platinum plus etoposide treatment and had relapse or progression at ≥ 90 days after completion of first-line treatment. A total of 162 patients (intent-to-treat population) were randomly assigned between July 2013 and July 2018 to a maximum of six 3-week cycles of carboplatin at AUC 5 on day 1 plus etoposide at 100 mg/m² from day 1 to day 3 (n = 81) or oral topotecan at 2.3 mg/m² from day 1 to day 5. The primary endpoint was progression-free survival on central review.
Median follow-up was 22.7 months. Median progression-free survival was 4.7 months (90% confidence interval [CI] = 3.9–5.5 months) in the combination group vs 2.7 months (90% CI = 2.3–3.2 months) in the topotecan group (hazard ratio [HR] = 0.57, 90% CI = 0.41–0.73; P = .0041).
Among the 156 patients with available data, 58% of the combination group and 68% of the topotecan group received third-line chemotherapy after study treatment. Median overall survival was 7.5 months (95% CI = 5.4–9.5 months) in the combination group vs 7.4 months (95% CI = 6.0–8.7 months) in the topotecan group (HR = 1.03, 95% CI = 0.87–1.19, P = .94).
Objective response was observed in 49% vs 25% of patients (P = .0024) and median duration of response was 5.4 months vs 4.1 months. At 6 months, 31% vs 10% of patients had not experienced a disease progression event.
The most frequent grade 3 or 4 adverse events were neutropenia (14% in the combination group vs 22% in the topotecan group), thrombocytopenia (31% vs 36%), anemia (25% vs 21%), febrile neutropenia (6% vs 11%), and asthenia (9% vs 10%). Serious adverse events with hospitalization occurred in 37% vs 43% of patients.
Treatment-related adverse events led to treatment discontinuation in 17% vs 12% of patients, with the most common cause being thrombocytopenia. Two treatment-related deaths occurred in the topotecan group—both due to febrile neutropenia with sepsis—and none occurred in the combination group.
The investigators concluded, “Our results suggest that carboplatin plus etoposide rechallenge can be considered as a reasonable second-line chemotherapy option for patients with sensitive relapsed small cell lung cancer.”
Christos Chouaid, MD, of the Service de Pneumologie, CHI Créteil, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Amgen and the French Lung Cancer Group (Groupe Français de Pneumo-Cancérologie). For full disclosures of the study authors, visit thelancet.com.