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PURPOSE Although level 1 evidence supports 45-Gy twice-daily radiotherapy as standard for limited-stage small-cell lung cancer, most patients receive higher-dose once-daily regimens in clinical practice. Whether increasing radiotherapy dose improves outcomes remains to be prospectively demonstrated. METHODS This phase III trial, CALGB 30610/RTOG 0538 (ClinicalTrials.gov identifier: NCT00632853 ), was conducted in two stages. In the first stage, patients with limited-stage disease were randomly assigned to receive 45-Gy twice-daily, 70-Gy once-daily, or 61.2-Gy concomitant-boost radiotherapy, starting with either the first or second (of four total) chemotherapy cycles. In the second stage, allocation to the 61.2-Gy arm was discontinued following planned interim toxicity analysis, and the study continued with two remaining arms. The primary end point was overall survival (OS) in the intention-to-treat population. RESULTS Trial accrual opened on March 15, 2008, and closed on December 1, 2019. All patients randomly assigned to 45-Gy twice-daily (n = 313) or 70-Gy once-daily radiotherapy (n = 325) are included in this analysis. After a median follow-up of 4.7 years, OS was not improved on the once-daily arm (hazard ratio for death, 0.94; 95% CI, 0.76 to 1.17; P = .594). Median survival is 28.5 months for twice-daily treatment, and 30.1 months for once-daily treatment, with 5-year OS of 29% and 32%, respectively. Treatment was tolerable, and the frequency of severe adverse events, including esophageal and pulmonary toxicity, was similar on both arms. CONCLUSION Although 45-Gy twice-daily radiotherapy remains the standard of care, this study provides the most robust information available to help guide the choice of thoracic radiotherapy regimen for patients with limited-stage small-cell lung cancer.

7506 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.