Adding Ganetespib to Docetaxel Does Not Improve Salvage Therapy Outcomes for Patients With Advanced NSCLC

The addition of ganetespib to docetaxel does not improve efficacy for salvage therapy in patients with advanced stage non-small cell lung cancer (NSCLC) with an adenocarcinoma histology,  according to results of the GALAXY-2 trial presented at the International Association for the Study of Lung Cancer (IASLC) 17th Annual World Conference on Lung Cancer (WCLC) in Austria.¹

GALAXY-2 is a randomized, international, open-label study of docetaxel with or without ganetespib, a highly potent inhibitor of heat shock protein 90 (Hsp90), which functions as a chaperone to stabilize oncoproteins. Ganetespib previously showed efficacy in combination with docetaxel over docetaxel alone in second-line therapy of patients with advanced lung adenocarcinoma in a phase 2 study.

677 patients with stage IIIB or stage IV NSCLC with adenocarcinoma histology, EGFR and ALK wild-type who were diagnosed more than 6 months prior to the study were randomly assigned to receive either docetaxel alone (335 patients) or docetaxel plus ganetespib (337 patients). Patients in the first arm received docetaxel at 75mg/m² on day 1 of a 3 week cycle and patients in the second arm received docetaxel plus ganetespib at 150 mg/m² on days 1 and 15 of each cycle. Patients were stratified by performance status, lactate dehydrogenase (LDH) level, and geographic region.

Sixty percent of patients were female, 68% were younger than 65 years old, 18% were never-smokers, and 36% had a performance status of 0.

The median number of cycles delivered was 5 in the ganetespib plus docetaxel arm and 4 in the docetaxel only arm.

There was no significant difference in median overall survival (OS) between the 2 arms. Patients who were treated with ganetespib plus docetaxel had a median OS of 10.9 months compared with 10.5 months in patients treated with docetaxel alone.

Median progression-free survival (PFS) was also similar between the 2 arms: 4.2 for ganetespib plus docetaxel versus 4.3 months for docetaxel alone. There was no improvement with the addition of ganetespib for any secondary endpoint, including survival in the eLDH, EGFR and ALK-negative populations, response rate, or progression due to new metastatic lesions. The most common grade 3 and 4 treatment-related adverse event in both arms was neutropenia.

Reference

1. Pillai RN, Fennell DA, Kovcin V, et al. Phase 3 study of ganetespib, a heat shock protein 90 inhibitor, with docetaxel versus docetaxel in advanced non-small cell lung cancer (GALAXY-2). Paper presented at: International Association for the Study of Lung Cancer 17th World Conference on Lung Cancer; December 2016; Vienna, Austria.