Hsp90 Inhibition With Ganetespib as a Lung Cancer Treatment

Suresh S. Ramalingam, MD, a professor of medical oncology at the Winship Cancer Institute of Emory University in Atlanta, Georgia, discusses the investigation of the heat shock protein (Hsp) 90 inhibitor ganetespib as a treatment for patients with advanced lung cancer.

Heat shock proteins chaperone newly formed proteins to become structurally active and perform their biologic function, Ramalingam notes. Blocking this process by the inhibition of Hsp90 with an agent like ganetespib renders these new proteins inactive. Altogether, Ramalingam notes, there are over 200 known proteins associated with Hsp90, many of which are important to the development of lung cancer, including EGFR and ALK.

The promise with ganetespib is that by inhibiting Hsp90, multiple oncoproteins that fuel lung cancer would also be simultaneously inhibited. This theory was tested in the phase II GALAXY-1 trial that explored ganetespib as a second-line treatment for patients with advanced lung adenocarcinoma. When compared to docetaxel, ganetespib improved overall survival by 2.4 months. Moreover, Ramalingam notes, these outcomes were more pronounced in patients diagnosed at least 6 months prior to treatment, with an overall survival improvement of 4.3 months.

Clinical Pearls

As it stands, this is the first randomized trial to document efficacy for Hsp90 inhibition in cancer, Ramalingam suggests. If this remains true in a phase III trial there will be broad implications in other types of cancer.

• Several proteins are associated with Hsp90, many of which are important to the development of lung cancer
• The phase II GALAXY-1 trial explored the Hsp90 inhibitor ganetespib as a second-line treatment for patients with advanced lung adenocarcinoma
• In GALAXY-1, second-line ganetespib improved overall survival by 2.4 months longer than docetaxel
• GALAXY-1 was the first randomized trial to document the efficacy of an Hsp90 inhibitor in cancer