Randomized Phase III Study of Ganetespib, a Heat Shock Protein 90 Inhibitor, With Docetaxel Versus Docetaxel in Advanced Non-Small-Cell Lung Cancer (GALAXY-2).

Abstract

PURPOSE:

Ganetespib, a highly potent heat shock protein 90 inhibitor, blocks multiple oncogenic pathways, resulting in antitumor activity. We evaluated the combination of ganetespib and docetaxel for second-line therapy of patients with advanced adenocarcinoma of the lung.

PATIENTS AND METHODS:

In this international phase III trial, patients with stage IIIB or IV adenocarcinoma diagnosed > 6 months before study entry and 1 prior systemic therapy were randomly assigned (1:1) to ganetespib 150 mg/m2 on days 1 and 15 with docetaxel 75 mg/m2 on day 1 of a 21-day cycle or to docetaxel alone. The primary end point was overall survival (OS).

RESULTS:

Of 677 enrolled patients, 335 were randomly assigned to ganetespib and docetaxel and 337 were assigned to docetaxel. The trial was stopped early as a result of futility at a planned interim analysis. The median OS time was 10.9 months (95% CI, 9.0 to 12.3 months) in the ganetespib and docetaxel arm compared with 10.5 months (95% CI, 8.6 to 12.2 months) in docetaxel arm (hazard ratio [HR], 1.11; 95% CI, 0.899 to 1.372; P = .329). Median progression-free survival was 4.2 months in the ganetespib and docetaxel arm and 4.3 months in the docetaxel arm (HR, 1.16; 95% CI, 0.96 to 1.403; P = .119). The addition of ganetespib did not improve outcomes compared with docetaxel alone for any secondary end point, including survival in the elevated lactate dehydrogenase or EGFR and ALK wild-type populations. The most common grade 3 or 4 adverse event in both arms was neutropenia (30.9% with ganetespib and docetaxel v 25% with docetaxel).

CONCLUSION:

The addition of ganetespib to docetaxel did not result in improved survival for salvage therapy of patients with advanced-stage lung adenocarcinoma.

• Authors: Rathi N Pillai, Dean A Fennell, Vladimir Kovcin, Tudor-Eliade Ciuleanu, Rodryg Ramlau, Dariusz Kowalski, Michael Schenker, Ilker Yalcin, Florentina Teofilovici, Vojo M Vukovic, Suresh S Ramalingam
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 38 Issue 6 Pg. 613-622 (02 20 2020) ISSN: 1527-7755 [Electronic] United States
• PMID: 31829907 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• HSP90 Heat-Shock Proteins
• STA 9090
• Triazoles
• Docetaxel

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, mortality)
• Docetaxel (therapeutic use)
• Female
• HSP90 Heat-Shock Proteins (antagonists & inhibitors)
• Humans
• Lung Neoplasms (drug therapy, mortality)
• Male
• Middle Aged
• Progression-Free Survival
• Salvage Therapy (methods)
• Treatment Outcome
• Triazoles (therapeutic use)