Phase II study of RAD001 (Everolimus) in previously treated small cell lung cancer (SCLC)

19017 Background: The mammalian Target of Rapamycin (mTOR) plays a central role in the PI3K/AKT signaling pathway, which may be important in the proliferative and antiapoptotic signaling in SCLC. RAD001 is an orally administered mTOR inhibitor with dose-dependent in vitro activity in SCLC cell lines and potent in vivo growth inhibition in xenograft models. Methods: Eligible patients (pts) had pathologically documented SCLC that relapsed after 1–2 prior chemotherapy regimens, ECOG performance status (PS) 0–2, and adequate bone marrow, kidney and liver function. Pts with untreated or symptomatic brain metastasis were excluded. RAD001 was administered orally continuously at a daily dose of 10 mg until disease progression or unacceptable toxicity. A cycle was 3 weeks with response assessment after every 2 cycles. The primary endpoint was the disease non-progression rate. Using a 2-stage design, 21 pts will be enrolled in the first stage. If ≥7 pts show disease stability or response, 21 additional pts will be accrued in the second stage. PI3K/AKT signaling pathway proteins (PTEN, AKT, pAKT, p-S6, p-4E-BP1) expression will be assessed by immunohistochemistry in baseline tumor tissue and will be correlated with response. Results: 17 pts have been enrolled: median age- 63 years (44 - 80); males- 6 (35%); PS0- 35%; PS1- 65%. Prior chemotherapy: Platinum/etoposide: 17 (100%), 2nd line- 2 (12%); prior radiation: chest- 8/17 (47%); brain- 9/17 (53%). 11 pts had sensitive relapses (i.e. >60 days from first-line chemotherapy completion). 1 pt did not complete the first cycle of RAD001, 5 received 1 cycle, and 10 (59%) ≥2 cycles; number of days on treatment: median- 42 days (3−117+). In 16 evaluable pts, there were no objective responses; 3 pts had stable disease (19%) as best response while 13 pts had progressive disease (81%). Duration of stable disease: 69 - 117+ days. No grade 3 or 4 toxicities were encountered. Grade 2 toxicities were as follows: fatigue (4), thrombocytopenia (3), elevated transaminases (2), anemia (2), rash (2), hypertriglyceridemia (1), and hypermagnesemia (1). Conclusions: Preliminary results show that RAD001 is well tolerated but has low activity as a single agent in unselected, previously treated pts with SCLC. Updated results and biomarker analysis will be available for presentation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis