Long-Term Results of NRG Oncology RTOG 0617: Standard- Versus High-Dose Chemoradiotherapy With or Without Cetuximab for Unresectable Stage III Non–Small-Cell Lung Cancer

Abstract

PURPOSE RTOG 0617 compared standard-dose (SD; 60 Gy) versus high-dose (HD; 74 Gy) radiation with concurrent chemotherapy and determined the efficacy of cetuximab for stage III non–small-cell lung cancer (NSCLC). METHODS The study used a 2 × 2 factorial design with radiation dose as 1 factor and cetuximab as the other, with a primary end point of overall survival (OS). RESULTS Median follow-up was 5.1 years. There were 3 grade 5 adverse events (AEs) in the SD arm and 9 in the HD arm. Treatment-related grade ≥3 dysphagia and esophagitis occurred in 3.2% and 5.0% of patients in the SD arm v 12.1% and 17.4% in the HD arm, respectively ( P = .0005 and < .0001). There was no difference in pulmonary toxicity, with grade ≥3 AEs in 20.6% and 19.3%. Median OS was 28.7 v 20.3 months ( P = .0072) in the SD and HD arms, respectively, 5-year OS and progression-free survival (PFS) rates were 32.1% and 23% and 18.3% and 13% ( P = .055), respectively. Factors associated with improved OS on multivariable analysis were standard radiation dose, tumor location, institution accrual volume, esophagitis/dysphagia, planning target volume and heart V5. The use of cetuximab conferred no survival benefit at the expense of increased toxicity. The prior signal of benefit in patients with higher H scores was no longer apparent. The progression rate within 1 month of treatment completion in the SD arm was 4.6%. For comparison purposes, the resultant 2-year OS and PFS rates allowing for that dropout rate were 59.6% and 30.7%, respectively, in the SD arms. CONCLUSION A 60-Gy radiation dose with concurrent chemotherapy should remain the standard of care, with the OS rate being among the highest reported in the literature for stage III NSCLC. Cetuximab had no effect on OS. The 2-year OS rates in the control arm are similar to the PACIFIC trial.

Efficacy and safety of immune checkpoint inhibitor consolidation after chemoradiation in patients of Asian ethnicity with unresectable stage III non‐small cell lung cancer: Chinese multicenter report and literature review

“…2,3 Historically, the five-year overall survival (OS) rate for locally advanced NSCLC patients undergoing definitive concurrent chemoradiotherapy (cCRT) treatment has been reported to be 20%-30%. [4][5][6] Despite countless efforts to improve the prognosis of these patients over recent decades, little progress had been made prior to the advent of immune checkpoint inhibitor (ICI) therapy.…”

Association of Planning Target Volume with Patient Outcome in Inoperable Stage III NSCLC Treated with Chemoradiotherapy: A Comprehensive Single-Center Analysis

“…In 2011, Salama et al conducted a secondary analysis of the Cancer and Leukemia Group B (CALBG) 30,105 trial and found that a larger PTV and smaller total lung volume/PTV ratio were associated with increasing pulmonary toxicity in a univariate analysis [ 12 ]. Initial and long-term results of the Radiation Therapy Oncology Grou (RTOG) 0617 trial confirmed PTV as a prognosticator in inoperable stage III NSCLC treated with concurrent CRT in univariate and multivariate analyses [ 13 , 14 ]. Moreover, radiation therapy quality assurance within the PROCLAIM trial (Randomized Phase III Trial of Pemetrexed-Cisplatin or Etoposide-Cisplatin Plus Thoracic Radiation Therapy Followed by Consolidation Chemotherapy in Locally Advanced Nonsquamous Non-Small-Cell Lung Cancer) revealed that stage IIIB and PTV were associated with major violations in the delivered treatment plans [ 15 ].…”

Risk factors for esophagitis after hypofractionated palliative (chemo)radiotherapy for non-small cell lung cancer

“…The RTOG 0617 study compared curative standard-dose (60 Gy) versus high-dose (74 Gy) radiation with concurrent chemotherapy and determined the efficacy of cetuximab for stage III (NSCLC) [20].…”