A multicenter phase II study of ganetespib monotherapy in patients with genotypically defined advanced non-small cell lung cancer

Mark A. Socinski, Jonathan Goldman, Iman El-Hariry, Marianna Koczywas, Vojo Vukovic, Leora Horn, Eugene Paschold, Ravi Salgia, Howard West, Lecia V. Sequist, Philip Bonomi, Julie Brahmer, Lin Chi Chen, Alan Sandler, Chandra P. Belani, Timothy Webb, Harry Harper, Mark Huberman, Suresh Ramalingam, Kwok Kin WongFlorentina Teo Filovici, Wei Guo, Geoffrey I. Shapiro

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Abstract

Purpose: Ganetespib is a novel inhibitor of the heat shock protein 90 (Hsp90), a chaperone protein critical to tumor growth and proliferation. In this phase II study, we evaluated the activity and tolerability of ganetespib in previously treated patients with non-small cell lung cancer (NSCLC). Experimental Design: Patients were enrolled into cohort A (mutant EGFR), B (mutant KRAS), or C (no EGFR or KRAS mutations). Patients were treated with 200 mg/m2 ganetespib by intravenous infusion once weekly for 3 weeks followed by 1 week of rest, until disease progression. The primary endpoint was progression-free survival (PFS) at 16 weeks. Secondary endpoints included objective response (ORR), duration of treatment, tolerability, median PFS, overall survival (OS), and correlative studies. Results: Ninety-nine patients with a median of 2 prior systemic therapies were enrolled; 98 were assigned to cohort A (n = 15), B (n = 17), or C (n = 66), with PFS rates at 16 weeks of 13.3%, 5.9%, and 19.7%, respectively. Four patients (4%) achieved partial response (PR); all had disease that harbored anaplastic lymphoma kinase (ALK) gene rearrangement, retrospectively detected by FISH (n = 1) or PCR-based assays (n = 3), in crizotinib-naïve patients enrolled to cohort C. Eight patients (8.1%) experienced treatment-related serious adverse events (AE); 2 of these (cardiac arrest and renal failure) resulted in death. The most common AEs were diarrhea, fatigue, nausea, and anorexia. Conclusions: Ganetespib monotherapy showed a manageable side effect profile as well as clinical activity in heavily pretreated patients with advanced NSCLCs, particularly in patients with tumors harboring ALK gene rearrangement.

Original languageEnglish (US)
Pages (from-to)3068-3077
Number of pages10
JournalClinical Cancer Research
Volume19
Issue number11
DOIs
StatePublished - Jun 1 2013

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Socinski, M. A., Goldman, J., El-Hariry, I., Koczywas, M., Vukovic, V., Horn, L., Paschold, E., Salgia, R., West, H., Sequist, L. V., Bonomi, P., Brahmer, J., Chen, L. C., Sandler, A., Belani, C. P., Webb, T., Harper, H., Huberman, M., Ramalingam, S., ... Shapiro, G. I. (2013). A multicenter phase II study of ganetespib monotherapy in patients with genotypically defined advanced non-small cell lung cancer. Clinical Cancer Research, 19(11), 3068-3077. https://doi.org/10.1158/1078-0432.CCR-12-3381