Jeffrey D. Bradley, MD

As reported in the Journal of Clinical Oncology by Jeffrey D. Bradley, MD, and colleagues, long-term results of the phase III NRG Oncology/RTOG 0617 trial indicate that standard-dose radiotherapy should remain the standard of care in chemoradiotherapy for nonresectable stage III non–small cell lung cancer (NSCLC). The addition of cetuximab to treatment provided no survival benefit.

Study Details

In the 2 x 2 factorial trial, 549 patients were randomly assigned to receive either:

• Carboplatin/paclitaxel chemotherapy plus concurrent standard-dose radiotherapy at 60 Gy without (n = 166) or with cetuximab (n = 147)
• High-dose radiotherapy at 74 Gy without (n = 121) or with cetuximab (n = 110).

The primary endpoint was overall survival.

Key Findings

Median follow-up was 5.1 years. Median overall survival was 28.7 months in the standard-dose group vs 20.3 months in the high-dose group (P = .0072).

The addition of cetuximab did not improve progression-free or overall survival (P = .977 for overall survival with vs without cetuximab) and was associated with increased toxicity (treatment-related grade ≥ 3 toxicity in 87% vs 71%).

Five-year overall survival was 32.1% vs 23.0% (hazard ratio [HR] = 1.35, 95% confidence interval [CI] = 1.08–1.69) and 5-year progression-free survival was 18.3% vs 13.0% (HR = 1.22, 95% CI = 1.00–1.51).

Grade 5 adverse events occurred in three patients in the standard-dose group vs nine in the high-dose group. Treatment-related grade ≥ 3 dysphagia and esophagitis occurred in 3.2% and 5.0% of patients in the standard-dose group vs 12.1% and 17.4% in the high-dose group (P = .0005 and P < .0001). Grade ≥ 3 pulmonary toxicity occurred in 20.6% vs 19.3% of patients.

On multivariate analysis, factors significantly associated with improved overall survival were standard radiation dose, tumor location, institution accrual volume, esophagitis/dysphagia, planning target volume, and heart V5.

The investigators concluded, “A 60 Gy radiation dose with concurrent chemotherapy should remain the standard of care, with the [overall survival] rate being among the highest reported in the literature for stage III NSCLC. Cetuximab had no effect on [overall survival].”

Dr. Bradley, of the Department of Radiation Oncology, Siteman Cancer Center at Washington University School of Medicine, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by National Cancer Institute grants and Eli Lilly. For full disclosures of the study authors, visit ascopubs.org.