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Dr. Jack West is a medical oncologist and thoracic oncology specialist who is the Founder and previously served as President & CEO, currently a member of the Board of Directors of the Global Resource for Advancing Cancer Education (GRACE)

 

mTOR Inhibitors for Small Cell Lung Cancer
Author
Howard (Jack) West, MD

We've covered the modest activity of a few mTOR inhibitors in NSCLC (see prior post), so now we'll turn to SCLC. Everolimus, an oral mTOR inhibitor, has been studied at 10 mg by mouth daily in patients with relapsed SCLC and had received 1 or 2 prior regimens and no brain metastases (abstract here). The investigators did a preliminary analysis of 19 patients, among whom there were no responses, and only 3 achieved stable disease. Though tolerated well enough, there wasn't enough of a signal to move forward with it. The IV mTOR inhibitor temsirolimus (Torisel) has also been studied in a more favorable prognosis scenario of maintenance therapy after a good response to first line chemo for extensive stage SCLC (abstract here). A total of 85 patients were treated with either of two doses, 25 mg IV weekly, or ten times that amount, 250 mg IV weekly. The median survival of 8 months was reasonable, but it was notably better at the higher dose (6.6 months vs. 9.5 months). The problem was that these patients also tend to do well, and the patients receiving temsirolimus didn't do better than the investigators would have expected otherwise. Because of this, there was little enthusiasm for continuing with it as a single agent in SCLC, but there was more interest in adding it to chemo for SCLC.

In fact, there is a study moving forward, being sponsored by Novartis, the makers of everolimus, the oral mTOR inhibitor, in combination with cisplatin and etoposide as first line therapy for extensive stage SCLC. The first portion is primarily checking whether it's safe and feasible to combine these agents as a triplet, and there is more information about that trial here.

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