Randomized phase II trial comparing the efficacy of standard-dose with high-dose twice-daily thoracic radiotherapy (TRT) in limited disease small-cell lung cancer (LD SCLC).

Authors

Bjorn H. Gronberg

Bjorn Henning Gronberg

Department of Clinical and Molecular Medicine, NTNU, Norwegian University of Science and Technology and Department of Oncology, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway

Bjorn Henning Gronberg , Kristin Toftaker Killingberg , Øystein Fløtten , Maria Moksnes Bjaanæs , Tesfaye Madebo , Seppo Langer , Tine Schytte , Odd Terje Brustugun , Jan Nyman , Kristin Stokke , Tarje Onsøien Halvorsen

Organizations

Department of Clinical and Molecular Medicine, NTNU, Norwegian University of Science and Technology and Department of Oncology, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway, Department of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway, Department of Oncology, Oslo University Hospital, Oslo, Norway, Department of Pulmonology, Stavanger University Hospital, Stavanger, Norway, Department of Oncology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark, Department of Oncology, Odense University Hospital, Odense, Denmark, Section of Oncology, Drammen Hospital, Vestre Viken Health Trust, Drammen, Norway, Department of Oncology, Sahlgrenska University Hospital and Sahlgrenska Academy, Gothenburg, Sweden, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology and The Cancer Clinic, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway

Research Funding

Other
The Norwegian Cancer Society and The Liaison Committee for Education, Research and Innovation in Central Norway

Background: Concurrent chemoradiotherapy is the standard treatment of LD SCLC. Some patients are cured, but most relapse and better treatment is needed. 45 Gy in 30 fractions BID is the most recommended TRT-schedule. Studies suggest that a higher TRT-dose might prolong survival, but hitherto, this has not been confirmed in randomized trials. We aimed to investigate whether high-dose BID TRT of 60 Gy in 40 fractions was feasible, tolerated, and improved survival. Methods: Patients > 18 years, performance status (PS) 0-2 and confirmed LD SCLC were to receive 4 courses of platinum/etoposide and were randomized to BID TRT of 60 or 45 Gy. Responders were offered prophylactic cranial irradiation of 25-30 Gy. Primary endpoint was 2-year survival; secondary endpoints were toxicity, progression free survival (PFS), and overall survival (OS). To demonstrate a 25% improvement of 2-year survival from 53% to 66% with a one-sided α = .10 and β = .80, 75 patients were required on each arm. Results: Between 2014-2018, 176 patients were enrolled at 22 Scandinavian hospitals. 160 completed TRT per protocol and were eligible for the present analyses (60 Gy: n = 84, 45 Gy: n = 76). Median age was 65, 58% women, 90% PS 0-1. There were no significant differences in grade 3–4 esophagitis (60 Gy: 19%, 45 Gy: 18%, p = .92) or grade 3–4 pneumonitis (60 Gy: 4%, 45 Gy: 0%, p = .10). There was a trend towards more neutropenic infections on the 45 Gy arm (60 Gy: 21%, 45 Gy: 36%, p = .05). There were no significant differences in other grade 3-4 toxicity. Three patients died during the study treatment period (60 Gy: one neutropenic infection and one aortic dissection; 45 Gy: one thrombocytopenic bleeding). There were no statistically significant differences in response rates (60 Gy: 88% [95% CI 81-95], 45 Gy: 85% [95% CI 76-93], p = .52) or median PFS (60 Gy: 20 months [95% CI 11-29], 45 Gy: 14 months [95% CI 10-19], p = .31). Significantly more patients on the 60 Gy arm were alive after 2 years (60 Gy: 73% [95% CI 63-83], 45 Gy: 46% [95% CI 36-60], p = .001), and they had a significantly longer median overall survival (60 Gy: 42 months [95% CI 32-51], 45 Gy: 23 months [95% CI 17-28], HR .63 [95% CI .41-.96], p = .031). Conclusions: LD SCLC patients who received BID TRT of 60 Gy had a statistically significant and numerically substantial benefit in terms of 2-year survival (primary endpoint) and median overall survival compared with those who received BID TRT of 45 Gy. The higher TRT dose did not cause more toxicity than the standard dose. Clinical trial information: NCT02041845

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Abstract Details

Meeting

2020 ASCO Virtual Scientific Program

Session Type

Oral Abstract Session

Session Title

Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers

Track

Lung Cancer

Sub Track

Small Cell Lung Cancer

Clinical Trial Registration Number

NCT02041845

Citation

J Clin Oncol 38: 2020 (suppl; abstr 9007)

DOI

10.1200/JCO.2020.38.15_suppl.9007

Abstract #

9007

Abstract Disclosures