Randomized phase 3 study of the anti-disialoganglioside antibody dinutuximab and irinotecan vs irinotecan or topotecan for second-line treatment of small cell lung cancer

Introduction: Topotecan is approved as second-line treatment for smal l ce l l lung cancer (SCLC). Irinotecan is also frequently used given its more convenient schedule and superior tolerability. Preclinical studies support dis-ialoganglioside (GD2) as an SCLC target and the combination of dinutuximab, an anti-GD2 antibody, plus iri-notecan in this setting. We tested dinutuximab/irinotecan versus irinotecan or topotecan as second-line therapy in relapsed/refractory (RR) SCLC. Materials and methods: Patients with RR SCLC and Easter n Cooperative Oncolog y Group performance status 0-1 were randomized 2:2:1 to receive dinutuximab 16-17.5 mg/m(2) intravenous (IV)/irinotecan 350 mg/m(2) IV (day 1), irinotecan 350 mg/m(2) IV (day 1), or topotecan 1.5 mg/m(2) IV (days 1-5) in 21-day cycles. The prima r y endpoint was overa l l survival (OS); seconda r y endpoints were progression-free survival (PFS), objective response rate (ORR; complete response [CR] + partial response [PR]), and clinical benefit rate (CBR; CR + PR + stable disease). Safety/tolerability were also assessed. Results: A total of 471 patients were randomized to dinutuximab/irinotecan (n = 187), irinotecan (n = 190), or topotecan (n = 94). Age, sex, performance status, prior therapies, and metastatic disease sites were similar between groups. Survival and response rates were not improved for patients receiving dinutuximab/irinotecan versus those receiving irinotecan or topotecan (median OS 6.9 vs 7.0 vs 7.4 months [p = 0.3132]; median PFS 3.5 vs 3.0 vs 3.4 months [p = 0.3482]; ORR confirmed 17.1% vs 18.9% vs 20.2% [p = 0.8043]; and CBR 67.4% vs 58.9% vs 68.1% [p = 0.0989]), respectively. Grade 3/4 adverse events (>= 5% receiving dinutuximab/irinotecan) included neutropenia, anemia, diarrhea, and asthenia. Conclusions: Dinutuximab/irinotecan treatment did not result in improved OS in RR SCLC versus irinotecan alone. Irinotecan administered every 21 days demonstrated comparable activity to topotecan administered daily x 5 every 21 days.