|The following article features coverage from the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Once-daily, high-dose thoracic radiotherapy (TRT) does not significantly improve survival compared with lower-dose, twice-daily TRT for limited-stage small cell lung cancer (LSCLC), according to phase 3 trial results presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.
There is Level 1 evidence supporting 45 Gy twice-daily TRT for 3 weeks in LSCLC, but the majority of patients are treated with a high dose of daily TRT in clinical practice, said Jeffrey A. Bogart, MD, of SUNY Upstate Medical University in Syracuse, New York, who presented the trial results at the meeting.
The trial, CALGB 30610/RTOG 0538 (ClinicalTrials.gov Identifier: NCT00632853), was designed to determine if administering once-daily, high-dose TRT would improve overall survival (OS), compared with 45 Gy twice-daily TRT in patients with LSCLC also receiving chemotherapy.
The trial was conducted in 2 stages. In the first stage, patients were randomized to 45 Gy twice daily for 3 weeks, 70 Gy once daily for 7 weeks, or 61.2 Gy concomitant boost for 5 weeks.
The second stage involved planned discontinuation of 1 high-dose arm based on an interim toxicity analysis, with patients then randomized 1:1 in the 2 remaining arms. TRT was given starting with either the first or second of 4 total chemotherapy cycles.
Ultimately, the concomitant-boost TRT arm was dropped, and patients were randomized to the other 2 arms. Dr Bogart presented data from the 638 patients who were randomized to 45 Gy twice-daily TRT (n = 313) or 70 Gy once-daily TRT (n = 325).
The patients had a median age of 63 years, 87% were White, 52% were women, and 95% had a performance status of 0 to 1. The chemotherapy backbone was cisplatin (81.3%) or carboplatin (18.7%).
At a median follow-up of 4 years, there was no significant difference in OS between once-daily and twice-daily TRT. The median OS was 30.5 months and 28.5 months, respectively (hazard ratio [HR], 0.94; 95% CI, 0.75-1.17, P =.591).
The 2-year OS was 56% for once-daily TRT and 58% for twice-daily TRT. The 4-year OS was 34% and 29%, respectively.
There was no significant difference in progression-free survival (PFS) between the arms. The median PFS was 14.2 months with once-daily TRT and 13.5 months with twice-daily TRT (HR, 0.98; 95% CI, 0.8-1.2; P =.857).
The 2-year PFS was 36% in both arms. The 5-year PFS was 24% with once-daily TRT and 25% with twice-daily TRT.
Rates of grade 3 or higher adverse events were largely similar between the arms. Common grade 3 or higher adverse events included febrile neutropenia (12.6% with once-daily TRT vs 13.6% with twice-daily TRT), dehydration (13% vs 14.2%), dyspnea (7.0% vs 4.3%), esophageal pain (12% vs 11%), and dysphagia (11.3% vs 9.5%).
There were 5 fatal adverse events in the once-daily TRT arm and 2 in the twice-daily TRT arm that were considered possibly, probably, or definitely treatment-related.
“CALGB 30610 failed to prove that 70 Gy once-daily radiotherapy significantly improves OS compared with standard 45 Gy twice-daily radiotherapy,” Dr Bogart said. “Outcomes in the 70 Gy cohort provide the best evidence available in support of once-daily, high-dose radiotherapy in limited-stage small cell lung cancer, but the study was not designed to assess whether 70 Gy high-dose daily radiotherapy was non-inferior to 45 Gy [twice daily].”
Disclosures: This research was supported by the National Institutes of Health. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Read more of Cancer Therapy Advisor’s coverage of the 2021 ASCO Annual Meeting by visiting the conference page.
Bogart JA, Wang XF, Masters GA, et al. Phase 3 comparison of high-dose once-daily (QD) thoracic radiotherapy (TRT) with standard twice-daily (BID) TRT in limited stage small cell lung cancer (LSCLC): CALGB 30610 (Alliance)/RTOG 0538. J Clin Oncol. 2021;39:(suppl 15; abstr 8505). doi:10.1200/JCO.2021.39.15_suppl.8505