Long-Term Results of RTOG 0617: A Randomized Phase 3 Comparison of Standard Dose Versus High Dose Conformal Chemoradiation Therapy +/- Cetuximab for Stage III NSCLC

Abstract

concurrent chemoradiotherapy for locally advanced non-small cell lung cancer (NSCLC). We performed a prospective trial examining dose-painted intensity-modulated radiotherapy (IMRT) as a strategy to improve the efficacy and safety of chemoradiotherapy for NSCLC. Materials/Methods: Patients with inoperable stage IIB-III NSCLC and ECOG performance status 0-2 who underwent staging PET were eligible for this single-arm study. All patients were treated with a 25-fraction course of dose-painted IMRT. Tumors or lymph nodes with MTV exceeding 25 cc were deemed "high risk" and received 65 Gy. Lesions smaller than 25 cc were considered "low risk" and treated with 57 Gy until November 2014, when the study was amended to reduce the prescription dose for such lesions to 52.5 Gy. All patients received concurrent weekly carboplatin (AUC 2) and paclitaxel (45 mg/m 2) during radiotherapy, and consolidation chemotherapy with the same agents was optional. Patients underwent post-treatment PET 12-16 weeks after completion of IMRT. The primary study endpoint was the absence of high residual metabolic activity (maximum SUV > 6) in the lungs and regional lymph nodes on post-treatment PET. Results: Thirty-five enrolled subjects with 116 hypermetabolic tumors and lymph nodes were eligible for analysis. The primary endpoint was met for 24/30 patients (80%) who underwent post-treatment PET, satisfying our pre-specified efficacy objective. Median follow-up duration for living patients is 17.0 months. Median survival time has not been reached. One and two-year actuarial rates of overall survival are 71% and 51%, respectively. Twenty-three patients (66%) have developed disease progression. Progression in a tumor or lymph node targeted with radiotherapy was observed in five patients at the time of first disease progression. Treating progression in other sites and death without progression as competing risks, the two-year cumulative incidence rate of local disease progression in 25 high-risk lesions is 9%. The two-year cumulative incidence rate of local disease progression in the 91 low-risk lesions that were treated with a low radiotherapy dose is 3%. Conclusion: Dose-painted IMRT based on pre-treatment PET metrics with concurrent chemotherapy for locally advanced NSCLC yields high rates of metabolic response, local disease control, and overall survival. This strategy should be pursued to maximize the therapeutic ratio of radiotherapy in this setting.

Three-Year Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC—Update from PACIFIC

“…[1][2][3] The historical standard of care for patients with unresectable stage III NSCLC was platinum-based doublet chemotherapy concurrent with radiotherapy (chemoradiotherapy [CRT]) with curative intent; however, patient prognosis with this treatment was poor, with 5-year survival rates of approximately 15 to 30%. 4,5 In 2017, management of stage III NSCLC changed with publication of results from the PACIFIC trial and subsequent worldwide health authority approvals of durvalumab in this setting.…”

Small‐spot intensity‐modulated proton therapy and volumetric‐modulated arc therapies for patients with locally advanced non‐small‐cell lung cancer: A dosimetric comparative study

“…Radiotherapy combined with chemotherapy is standard treatment for stage III NSCLC patients with unresectable tumors, but the potential toxic effects of radiation limit the feasibility for delivering adequate tumoricidal dose to targets in most patients . With photon radiation and concurrent chemotherapy, the long‐term results from RTOG 0617 reported 5‐year overall survival (5‐year OS) of 32.1% (standard dose arm with 60 Gy) and 23% (high dose arm of 74 Gy) for unresectable NSCLC patients . The fact that dose escalation has led to worse overall survival is possibly due to higher cardiac toxicity .…”

Interdisciplinary multimodality management of stage III nonsmall cell lung cancer

“…In the non-concurrent setting, shortening the overall treatment time of radiotherapy led to a significant increase in 5-year overall survival [59]. In concurrent chemoradiotherapy, no regimen has been shown to be superior to 60 Gy delivered in 30 daily fractions of 2 Gy [60][61][62]. Dose escalation >60 Gy in 30 daily fractions by adding 2 Gy fractions up to 74 Gy was detrimental for survival.…”

“…Until now the clinical data with tyrosine kinase inhibitors (TKIs) are inconclusive [91]. Unfortunately, the RTOG0617 phase III trial did not show a beneficial effect of adding cetuximab to CCRT [61,62].…”