(HealthDay News) – Ganetespib has anticancer activity in KRAS-mutant non-small-cell lung cancer (NSCLC) cells, and works synergistically with other clinical agents to increase cell death; and sorafenib also has clinical activity in patients with KRAS-mutant NSCLC, according to two studies presented at the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer: Biology, Therapy, and Personalized Medicine, held from January 8 to 11 in San Diego.

Jaime Acquaviva, PhD, from Synta Pharmaceuticals Corporation in Lexington, MA, and colleagues investigated whether ganetespib is effective in suppressing cell signaling nodes responsible for KRAS-driven NSCLC cell survival. The researchers found that ganetespib displayed in vitro anticancer activity in KRAS-mutant NSCLC cell lines. Compared with monotherapy, combining ganetespib with antimitotics, alkylating agents, or topoisomerase agents resulted in a 44, 61, and 26% increase in cell death, respectively. In vivo experiments in mice demonstrated improved tumor growth inhibition with a combination of ganetespib and a phosphoinositide-3-kinase/mammalian target of rapamycin inhibitor.

Woulter W. Mellema, MD, from the VU University Medical Center in Amsterdam, Netherlands, and colleagues investigated the role of sorafenib in a phase II trial in 57 patients with KRAS-positive NSCLC. The treatment consisted of 400 mg sorafenib until disease progression or unacceptable toxicity. The median duration of treatment was nine weeks, and median duration of response, 32 weeks. Median progression-free and overall survival were 2.3 and 4.9 months, respectively.

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“Treatment with sorafenib has relevant clinical activity in patients with KRAS mutational status. Further randomized study with this agent is warranted,” Mellema and colleagues write

The authors of the first study are employees of Synta Pharmaceuticals Corp., which manufactures ganetespib.

Abstract – Acquaviva
Abstract – Mellema
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