Long-Term Survival Rates More Than Double Previous Estimates for Locally Advanced Lung Cancer


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Jeffrey D. Bradley, MD, FASTRO

Jeffrey D. Bradley, MD, FASTRO

THE LONG-TERM RESULTS of a phase III clinical trial indicate that survival rates for patients receiving chemoradiation for unresectable, locally advanced non–small cell lung cancer (NSCLC) may be more than twice as high as previous estimates, setting a new benchmark of survival for patients with inoperable stage III NSCLC. The trial, RTOG 0617, also confirms that a standard dose of radiation therapy is preferable to a higher dose and that cetuximab (Erbitux) offers no additional survival benefit for these patients. these findings were presented at the 59th Annual Meeting of the American Society for Radiation Oncology (ASTRO) in San Diego by Jeffrey D. Bradley, MD, FASTRO, the principal investigator of the RTOG 0617 trial and Professor of Radiation Oncology and Director of the S.L. King Center for Proton Therapy at the Washington University School of Medicine in St. Louis.1 

Study Details 

PATIENTS ENROLLED in this randomized trial were assigned to one of two chemoradiation dose groups. Standard-dose treatment consisted of 60-Gy total radiation dose, and high-dose patients received a 74-Gy total dose. Radiation was delivered in 2-Gy daily fractions through either intensity-modulated radiation therapy or three-dimensional conformal radiation therapy. All patients received concurrent weekly chemotherapy with paclitaxel and carboplatin. Patients also were randomized to receive either cetuximab or a placebo. 

Across the 185 institutions in the United States and Canada that participated in RTOG 0617, a total of 544 patients with unresectable stage III NSCLC were accrued, and 496 were eligible for analysis. The median patient age was 64 years, and most patients were male (59%) and white (41%). 

Survival rates at 5 years following chemoradiation were higher for patients in the standard-dose treatment arm than for those in the high-dose arm. Median overall survival following standard-dose treatment was 28.7 months (95% confidence interval [CI] = 24–38.4), compared with 20.3 months (95% CI = 18–24) for the high-dose cohort (hazard ratio 1.35, P = .004). Five-year overall survival rates were 32.1% and 23% for the standard-dose and high-dose arms, respectively (P = .004). Progression-free survival rates at 5 years were 18.3% and 13% for the standard-dose and high-dose arms, respectively (P = .055). 

On a multivariate analysis, differences in overall survival were driven by radiation dose (favoring the standard-dose regimen; P = .03), planning target volume (P = .022), the accrual volume of the treating institution (P = .017), presence of esophagitis/dysphagia (P = .008), and V5 heart dose/volume (P = .005). 

Treatment-related side effects were more pronounced with the high-dose regimen. There were three treatment-related deaths in the standard-dose arm, compared with nine in the high-dose arm. Rates of treatment-related grade 3 or higher toxicity for the standard-dose and high-dose arms, respectively, follow: dysphagia in 3.2% vs 12.1% (P < .0001); esophagitis in 5.0% vs 17.4% (P < .0001); and severe pulmonary events in 20.6% vs 19.3% (P > .05). 

Cetuximab (delivered as a 400-mg dose on day 1, then 250-mg doses weekly thereafter) did not confer a benefit for overall survival at 5 years. Median overall survival for patients who received cetuximab was 24 months (95% CI = 20.4–30), compared with 24 months (95% CI = 20.5–28.8) for those who did not (hazard ratio 1.0, P = .048). ■

DISCLOSURE: For full disclosures of the study authors, visit www.redjournal.org. 

REFERENCE 

1. Bradley JD, et al: Long-term results of RTOG 0617. 2017 ASTRO Annual Meeting. Abstract 227.



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