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

Martin J. Edelman, Mikhail Dvorkin, Konstatin Laktionov, Alejandro Navarro, Oscar Juan-Vidal, Vadim Kozlov, Gil Golden, Odette Jordan, C. Q. Deng, Dmitriy Bentsion, Christos Chouaid, Hristo Dechev, Afshin Dowlati, Natalia Fernández Núñez, Olexandr Ivashchuk, Ivane Kiladze, Tsira Kortua, Natasha Leighl, Aleksandr Luft, Tamta MakharadzeYoung Joo Min, Xavier Quantin

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Introduction: Topotecan is approved as second-line treatment for small cell lung cancer (SCLC). Irinotecan is also frequently used given its more convenient schedule and superior tolerability. Preclinical studies support disialoganglioside (GD2) as an SCLC target and the combination of dinutuximab, an anti-GD2 antibody, plus irinotecan 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 Eastern Cooperative Oncology Group performance status 0–1 were randomized 2:2:1 to receive dinutuximab 16–17.5 mg/m2 intravenous (IV)/irinotecan 350 mg/m2 IV (day 1), irinotecan 350 mg/m2 IV (day 1), or topotecan 1.5 mg/m2 IV (days 1–5) in 21-day cycles. The primary endpoint was overall survival (OS); secondary 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 × 5 every 21 days. ClinicalTrials.gov Identifier. NCT03098030.

Original languageEnglish
Pages (from-to)135-142
Number of pages8
JournalLung Cancer
StatePublished - Apr 2022


  • Antibodies, Monoclonal
  • Antineoplastic Combined Chemotherapy Protocols/therapeutic use
  • Humans
  • Irinotecan/therapeutic use
  • Lung Neoplasms/pathology
  • Neoplasm Recurrence, Local/pathology
  • Small Cell Lung Carcinoma/drug therapy
  • Topotecan/therapeutic use


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