High-Dose Once-Daily Thoracic Radiotherapy in Limited-Stage Small-Cell Lung Cancer: CALGB 30610 (Alliance)/RTOG 0538

Abstract

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.

Six versus four or five cycles of first‐line etoposide and platinum‐based chemotherapy combined with thoracic radiotherapy in patients with limited‐stage small‐cell lung cancer: A propensity score‐matched analysis of a prospective randomized trial

“…14 Some guidelines even recommend that 4 cycles be preferred in LS-SCLC. 8 Four cycles of chemotherapy were also recommended in a recent clinical study by Bogart J, 15 Grønberg 16 et al This choice might be attributed to the potential cumulative toxicity arising from the combination of high-intensity radiotherapy and chemotherapy. However, in the CONVERT trial 17 which was the phase 3 trial completed investigating thoracic radiotherapy in LS-SCLC, chemotherapy contained 4-6 cycles of EP every 3 weeks.…”

An Evidenced-Based Prior for Estimating the Treatment Effect of Phase III Randomized Trials in Oncology

“…To illustrate the potential value of estimating the probability of benefit, consider the results of two example phase III trials, the GEMPAX trial and CALGB 30610 (Alliance) / RTOG 0538, neither of which was included in the development of the phase III prior as both trials were recently published. 30,31 The GEMPAX trial compared second-line gemcitabine with paclitaxel versus gemcitabine alone for patients with metastatic pancreatic ductal adenocarcinoma. 30 GEMPAX showed an improvement in progression-free survival (HR 0.64, 95% CI 0.47 to 0.89) and overall response rate, but interpreted the primary endpoint of overall survival as “statistically negative” (HR 0.87, 95% CI 0.63 to 1.20) on the basis of a large P value (0.41).…”

Progress in radiotherapy for small‐cell lung cancer

“…In the C30610/RTOG-0538 trial, a further increase in dose to 70 Gy (70 Gy/35 fractions /2 Gy qd) was compared with the HFRT dose (45 Gy/30 fractions /1.5 Gy bid). 8 Respectively, the median OS was 30.1 and 28.5 months (p = 0.594), respectively, and the 5-year survival rates were 32% and 29%, respectively. The frequency of serious adverse events (including esophageal and pulmonary toxicities) was similar between the two groups.…”

“…Therefore, HFRT should be continued as the standard regimen. In the C30610/RTOG‐0538 trial, a further increase in dose to 70 Gy (70 Gy/35 fractions /2 Gy qd) was compared with the HFRT dose (45 Gy/30 fractions /1.5 Gy bid) 8 . Respectively, the median OS was 30.1 and 28.5 months ( p = 0.594), respectively, and the 5‐year survival rates were 32% and 29%, respectively.…”