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

Abstract

8107 Background: Everolimus (E) is an oral inhibitor of mammalian target of rapamycin (mTOR), a novel target for anti-cancer therapy that plays a central role in the PI3K/AKT signaling pathway and other pathways that mediate tumor growth, proliferation, and angiogenesis. E has shown preclinical activity in SCLC cell lines and xenograft models. Methods: Eligibility included SCLC with disease progression after up to 2 prior chemotherapy regimens, ECOG performance status (PS) 0–2, and adequate bone marrow, liver, and kidney function. Patients (pts) were treated with E 10 mg, orally, once daily. Primary endpoint was the disease control rate (DCR), i.e. complete response (CR), partial response (PR) and stable disease (SD), after 2 cycles of E (6 weeks) in pts who received at least 1 cycle. A 2-stage design was followed. PI3K/AKT signaling pathway molecular biomarkers (AKT, pAKT, PTEN, P-S6, p-4E- BP1) will be evaluated on baseline tumor tissue. Results: 40 pts were enrolled; 14 males/26 females; median age 64 years (44–80); PS 0: 17, PS 1: 23; prior chemotherapy status: 1 prior regimen/sensitive relapse (i.e. relapse >60 days from completion of first-line chemotherapy): 23 pts; 1 prior regimen/refractory: 4 pts; 2 prior regimens: 13 pts. 28 pts (70%) received ≥ 2 cycles of E, 7 (18%) 1 cycle and 5 (12%) did not complete the first cycle of E due to adverse events or early progression. Best response in 35 evaluable patients: 1 (3%) PR, 8 (23%) SD and 26 (74%) progression; DCR at 6 weeks was 26% with a duration of disease control of 2.7–6.3 months; median progression-free survival 1.4 months; and median overall survival 5.5 months. No grade 4 toxicity was seen. Grade 3 toxicities included thrombocytopenia (2), neutropenia (2), infection (1), pneumonitis (1), fatigue (1), elevated transaminases (1), hyperglycemia (1), diarrhea (1), and acute renal failure due to dehydration from diarrhea and poor oral intake (1). Conclusions: E is well tolerated but has limited single-agent antitumor activity in unselected patients with pretreated SCLC. [Table: see text]