New Chaperone-Targeting Ganetespib Prolongs Survival in Advanced Lung Cancer

CHICAGO―Adding the novel heat shock protein (HSP)-90 inhibitor ganetespib to docetaxel in salvage therapy is associated with prolonged overall survival (OS) compared to docetaxel alone among patients diagnosed with advanced adenocarcinoma lung cancer, report authors of the large randomized, first-in-class phase 2 GALAXY-1 clinical trial, presented at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting.

“This is the first randomized study to demonstrate therapeutic benefit with a heat shock protein inhibitor in patients with cancer,” reported lead author Suresh S. Ramalingam, MD, of the Winship Cancer Institute at Emory University in Atlanta, GA.  “Ganetespib combined with docetaxel was well tolerated with an acceptable safety profile in adenocarcinoma patients.”

A phase 3 GALAXY-3 trial is already under way, he noted.

HSP90 is a chaperone, a class of molecules involved in proteins assuming the functional configurations, or shapes, required to perform biologic functions. Proteins involved in lung tumor growth, including EGFR and ALK, require HSP-90, so blocking chaperones can disrupt these oncoproteins' contributions to tumor growth, Dr. Ramalingam explained.

This new anticancer strategy could also prove useful in circumventing tumor drug resistance, he noted.

A total of 252 patients diagnosed with adenocarcinoma of the lung, were randomly assigned 1:1 to receive docetaxel (75 mg/m2 on day 1 of a 3-week cycle) either with or without ganetespib (150 mg/m2 on days 1 and 15, on a 3-week cycle).

Patients in the ganetespib group had prolonged OS compared to docetaxel alone (9.8 vs 7.4 months; hazard ratio [HR], 0.73; P=0.041), Dr. Ramalingam reported.

An even more dramatic 67% OS prolongation was seen among patients treated at least 6 months after their initial diagnosis of advanced lung cancer (10.7 vs 6.4 months; HR, 0.55; P=0.0034). This is the patient population under study in the ongoing GALAXY-3 trial.

Approximately half of non-small cell lung cancers in the United States are adenocarcinomas, Dr. Ramalingam noted.

“Patients with this common form and stage of lung cancer urgently need more effective treatments,” he said.