The Hedgehog pathway inhibitor sonidegib in combination with etoposide and cisplatin may be safe and effective in patients with newly diagnosed extensive stage small cell lung cancer, a study published in Lung Cancer has shown.1

Because the Hedgehog pathway plays a role in tumor initiation and progression of small cell lung cancer, researchers hypothesized that that pharmacologic blockade of Smoothened, the key Hedgehog regulator, may inhibit these processes. Therefore, researchers sought to determine the maximum tolerated dose of sonidegib, in combination with etoposide and cisplatin in treatment-naive patients.

For the study, researchers enrolled 15 patients with newly diagnosed extensive stage small cell lung cancer. All participants received sonidegib 400 mg or 800 mg orally daily plus cisplatin and etoposide for 4 to 6 21-day cycles. Patients who achieved a response or who had stable disease continued sonidegib treatment until disease progression or unacceptable toxicity. The dose of sonidegib could be de-escalated to 200 mg daily if necessary.

Investigators ultimately determined 800 mg daily as the recommended phase 2 dose of sonidegib in this regimen.  Results showed that 79% (95% CI, 49-95) of the evaluable 14 patients achieved a partial response as 1 patient was removed due to toxicity.

Researchers found that the most common grade 3 or greater adverse events were neutropenia, anemia, creatine phosphokinase elevation, fatigue, and nausea.

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The study also demonstrated that 1 patient with SOX2 amplification remained progression-free on maintenance sonidegib after 27 months of therapy. Further, circulating tumor cell (CTC) count at baseline was associated with the presence of liver metastases and CTC count after 1 cycle of treatment was associated with overall survival.

Reference

  1. Pietanza MC, Litvak AM, Varghese AM, et al. A phase I trial of the hedgehog inhibitor, sonidegib (LDE225), in combination with etoposide and cisplatin for the initial treatment of extensive stage small cell lung cancer [published online ahead of print April 25, 2016]. Lung Cancer. doi: 10.1016/j.lungcan.2016.04.014.