Phase II study of everolimus (RAD001) in previously treated small cell lung cancer.
OBJECTIVE
Mammalian target of rapamycin (mTOR) is a promising target in small cell lung cancer (SCLC). We designed a phase II study of everolimus, an mTOR inhibitor, in previously treated, relapsed SCLC.


METHODS
Patients were treated with everolimus 10 mg orally daily until disease progression. The primary endpoint was disease control rate (DCR) at 6 weeks. PI3K/Akt signaling pathway biomarkers were evaluated on baseline tumor tissue.


RESULTS
A total of 40 patients were treated: 23 had 1 prior regimen/sensitive relapse, 4 had 1 prior regimen/refractory, and 13 had 2 prior regimens. Twenty-eight patients received 2 or more cycles of everolimus, 7 received 1 cycle, and 5 did not complete the first cycle. Best response in 35 evaluable patients: 1 (3%) partial response (in sensitive relapse), 8 (23%) stable disease, and 26 (74%) progression; DCR at 6 weeks was 26% (95% CI = 11-40). Median survival was 6.7 months and median time to progression was 1.3 months. Grade 3 toxicities included thrombocytopenia (n = 2), neutropenia (n = 2), infection (n = 2), pneumonitis (n = 1), fatigue (n = 1), elevated transaminases (n = 1), diarrhea (n = 2), and acute renal failure (n = 1). High phosphorylated AKT expression was modestly associated with overall survival (HR = 2.07; 95% CI = 0.97-4.43). Baseline S6 kinase protein expression was significantly higher in patients with disease control versus patients with progression (P = 0.0093).


CONCLUSIONS
Everolimus was well tolerated but had limited single-agent antitumor activity in unselected previously treated patients with relapsed SCLC. Further evaluation in combination regimens for patients with sensitive relapse may be considered.
University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
Ahmad
A
Tarhini
Athanasios
A
Kotsakis
William
W
Gooding
Yongli
Y
Shuai
Daniel
D
Petro
David
D
Friedland
Chandra P
CP
Belani
Sanja
S
Dacic
Athanassios
A
Argiris
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D018450:Disease Progression; D000068338:Everolimus; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016879:Salvage Therapy; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis
D000970:Antineoplastic Agents; D000068338:Everolimus; D020123:Sirolimus