Chemotherapy with or without maintenance sunitinib for untreated extensive-stage small cell lung cancer: A randomized, placebo controlled phase II study CALGB 30504 (ALLIANCE)

Abstract

BACKGROUND: Sunitinib (S) inhibits small cell lung cancer (SCLC) targets VEGFR1-3, PDGFR, and KIT. We tested whether giving S after chemotherapy (C) for extensive stage SCLC improves progression free survival (PFS). METHODS: CALGB 30504 was a randomized, double-blind, placebo (P) controlled phase II study for untreated SCLC, performance status 0-2, adequate organ function, and no S risk factors: bleeding, hypertension, or brain metastases. Enrollment was prior to C: cisplatin 80 mg/m2 or carboplatin AUC5 day 1 plus etoposide 100 mg/m2days 1-3 every 21 days 4-6 cycles. Patients without progression after C were stratified cisplatin vs carboplatin, and 4-5 vs 6 cycles C, and randomized 1:1 to P or S 37.5 mg daily until progression assessed every 6 weeks. Prophylactic cranial irradiation was offered to responders (CR or PR) to start about 4-6 weeks after C. S was held during radiation. Crossover from P to S was allowed at progression. Primary endpoint was PFS (from time of randomization) for maintenance (M) P vs S using a 1-sided log rank test with a=0.15; 80 randomized and treated patients provide »89% power to detect a hazard ratio (HR) of 1.67. RESULTS: Between 5/09 and 12/11, 144 enrolled and 138 received C. Ninety five were randomized to P vs S; 10 did not receive M due to progression, refusal, and AE (5 each arm). Eighty five received M, 41 P and 44 S. Demographics were balanced. M toxicities grade > 3 and incidence > 5% included (%): grade 3 (S: fatigue 19, neutrophils 10, leukocytes 7, platelets 7) (P: fatigue 5); grade 4 (S: 1case GI hemorrhage, 1case lipase) P zero; grade 5 zero both arms. Efficacy (90% CI): PFS on maintenance after C was P 2.3 mo (CI: 1.7-2.6) and S 3.8 mo (2.7-4.4) (HR=1.54, CI 1.03-2.32, p=0.04). Overall survival (OS) was P 6.7 mo (5.5-9.5) and S 8.8 mo (8.0-9.8) (HR=1.10, CI 0.71-1.70, p=0.36). At progression on P, 17 received S and among 14 evaluable 10 (71%) had stable disease receiving 2-9 cycles S. CONCLUSIONS: The primary objective was met showing improved PFS for maintenance S. There was a non-significant trend toward improved OS despite crossover design. S was well tolerated. Further study of sunitinib after chemotherapy for SCLC is justified. Clinical trial information: NCT00453154.