Addition of ganetespib to docetaxel improved response, survival in lung adenocarcinoma

  • June 13, 2013

CHICAGO — The addition of ganetespib to docetaxel induced higher overall response rates and extended survival compared with docetaxel alone as salvage therapy in patients with lung adenocarcinoma, according to phase 2 results presented at the ASCO Annual Meeting.

The heat shock protein class of inhibitors are “important chaperone proteins for several key cellular oncogenic proteins,” said Suresh S. Ramalingam, MD, chief of thoracic oncology and director of medical oncology at the Emory University School of Medicine.

Prior studies showed ganetespib (Synta), an HSP90 inhibitor, demonstrated a favorable safety profile and single-agent clinical activity.

In the GALAXY-1 study, Ramalingam and colleagues randomly assigned 252 patients with advanced lung adenocarcinoma to treatment with docetaxel plus ganetespib (n=125) or docetaxel alone (n=127).

Docetaxel was administered at 75 mg/m² on day 1 of a 3-week cycle. In the combination arm, docetaxel was given on day 1 and ganetespib was administered at 150 mg/ m² on days 1 and 15.

The co-primary endpoints were PFS in patients with elevated LDH levels or tumors harboring KRAS mutations. Key secondary endpoints included OS and PFS in all adenocarcinoma patients.

Study results demonstrated that median PFS was 4.5 months in the combination group and 3.2 months in the docetaxel-alone group (HR=0.84; 90% CI, 0.65-1.07). OS was 9.8 months in the combination group and 7.4 months among patients assigned to docetaxel alone (HR=0.82; 90% CI, 0.62-1.09).

In particular, patients whose time from diagnosis of metastatic disease to start of therapy was at least 6 months (n=175; 69% of patients) exhibited a 67% improvement in OS with the combination of ganetespib and docetaxel.

“Ganetespib was tolerated well in combination with docetaxel in this patient population with advanced stage lung adenocarcinoma,” Ramalingam said. “In this analysis, the combination of docetaxel with ganetespib improved OS compared with docetaxel alone, and the median OS was improved by approximately 30% in patients with lung adenocarcinoma. Based on these promising results, we have initiated a phase 3 trial for GALAXY-2 that will have a similar design but will only include a patient population of those <6 months from the time of diagnosis for salvage therapy of lung adenocarcinoma.”

Common adverse events included neutropenia (38% combination vs. 37% docetaxel), fatigue (4% vs. 3%), anemia (7% vs. 6%) diarrhea (3% vs. 0%) and fever with neutropenia (8% vs. 2%).

“This is the first randomized study to demonstrate therapeutic benefit with a heat shock protein inhibitor in patients with cancer,” Ramalingam said. “We hope that the ongoing phase 3 study will confirm our findings, as patients with this common form and stage of lung cancer urgently need more effective treatments.”

For more information:

Ramalingam SS. Abstract #CRA8007. Presented at: ASCO Annual Meeting; May 31-June 4, 2013; Chicago.

Disclosure: The researchers report consulting/advisory positions with and research funding/honoraria from with Synta Pharmaceuticals.

Perspective
Alex A. Adjei, MD, PhD, FACP

Alex A. Adjei

  • The Hsp90 inhibitors have been in the clinic for more than a decade. Earlier drugs were toxic and had limited efficacy. Ganetespib is a third-generation compound showing initial evidence of clinical activity. However, this is a phase 2 study, and in lung cancer, a plethora of such initially promising phase 2 studies have failed in larger phase 3 trials. Thus, we should await the results of the phase 3 trial of ganetespib before declaring victory, but we are cautiously optimistic.

    • Alex A. Adjei, MD, PhD
    • Senior vice president of clinical research
      Professor and chair, department of medicine
      Katherine Anne Gioia Chair in cancer medicine
      Roswell Park Cancer Institute
      Buffalo, N.Y.
  • Disclosures: Adjei reports no relevant financial disclosures.
Perspective

Marjorie G. Zauderer

  • Ganetespib, in combination with docetaxel, shows promising early results in lung adenocarcinoma. We’re hopeful about the outcome of an ongoing phase 3 study, which could help more patients with this form of advanced lung cancer access this promising drug.

    • Marjorie G. Zauderer, MD
    • Medical oncologist
      Thoracic Oncology Service
      Memorial Sloan-Kettering Cancer