A randomized phase II study of linsitinib (OSI-906) versus Topotecan in patients with relapsed small-cell lung cancer

Alberto A. Chiappori, Gregory A. Otterson, Afshin Dowlati, Anne M. Traynor, Leora Horn, Taofeek K. Owonikoko, Helen J. Ross, Christine L. Hann, Taher Abu Hejleh, Jorge Nieva, Xiuhua Zhao, Michael Schell, Daniel M. Sullivan

Research output: Contribution to journalArticlepeer-review

Abstract

Background. Treatment of relapsed small-cell lung cancer (SCLC) remains suboptimal. Insulin growth factor-1 receptor (IGF-1R) signaling plays a role in growth, survival, and chemoresistance in SCLC. Linsitinib is a potent IGF-1R tyrosine kinase inhibitor that potentially may be active against SCLC. Methods. In this phase II study,8 eligible patients were randomly assigned in a 1:2 ratio to topotecan (1.5 mg/m2 intravenously or 2.3mg/m2 orally, daily for 5days for4 cycles)or linsitinib (150mg orally twice daily until progression). The primary endpoint was progression-free survival. Patients with relapsed SCLC, platinum sensitive or resistant, performance status (PS) 0–2, and adequate hematologic, renal, and hepatic function were enrolled. Patients with diabetes, cirrhosis, and those taking insulinotropic agents were excluded. Crossover to linsitinibwas allowed at progression. Results. Fifteen patients received topotecan (8 resistant, 3 with PS 2) and 29 received linsitinib (16 resistant, 5 with PS 2). Two partial responses were observed with topotecan. Only 4 of 15 patients with topotecan and 1 of 29 with linsitinib achieved stable disease. Median progression-free survival was 3.0 (95% confidence interval [CI], 1.5–3.6) and 1.2 (95% CI, 1.1–1.4) months for topotecan and linsitinib, respectively (p = .0001). Median survival was 5.3 (95% CI, 2.2–7.6) and 3.4 (95% CI, 1.8–5.6) months for topotecan and linsitinib, respectively (p = .71). Grade 3/4 adverse events (>5% incidence) included anemia, thrombocytopenia, neutropenia/leukopenia, diarrhea, fatigue, dehydration, and hypokalemia for topotecan; and thrombocytopenia, fatigue, and alanine aminotransferase/aspartate aminotransferase elevations for linsitinib. Conclusion. Linsitinib was safe but showed no clinical activity in unselected, relapsed SCLC patients.

Original languageEnglish (US)
Pages (from-to)1163-1164
Number of pages2
JournalOncologist
Volume21
Issue number10
DOIs
StatePublished - Oct 2016

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'A randomized phase II study of linsitinib (OSI-906) versus Topotecan in patients with relapsed small-cell lung cancer'. Together they form a unique fingerprint.

Cite this