A Multicentered, Randomized Phase III Study of Definitive vs. Palliative Radiotherapy to Primary Tumor for Stage IV Non-Small Cell Lung Cancer with Less than Three Metastatic Organs: CSWOG China

Abstract

To investigate the local-regional progression-free survival (LPFS), overall survival (OS), progression-free survival (PFS), local control rate of primary tumor (LCRP), and toxicity of definitive radiotherapy (concurrent chemoradiotherapy of 63 Gy) compared with palliative radiotherapy (concurrent chemoradiotherapy of 45 Gy) to primary tumor in newly diagnosed stage Ⅳ non-small cell lung cancer with less than three metastatic organs. A randomized, multicentered phase Ⅲ study (ChicTR-TRC-13003749), in a 1:1 ratio, included patients with newly diagnosed stage Ⅳ NSCLC with less than three metastatic organs. The EGFR mutation was wide type or unknown mainly. The patients were divided into 63 Gy of definitive radiotherapy (D63) and 45 Gy of palliative radiotherapy (P45). The primary endpoints were LPFS, OS. Secondary endpoints included PFS, LCRP, objective response rate (ORR) and toxicity. Three hundred forty-four patients were enrolled in 14 cancer centers. The median LPFS for group D63 was 18 months (95% CI, 13.02 to 22.98) better than 13 months for group P45 (95% CI, 10.13 to 15.87). LPFS for 1, 2, and 5 years were 62.9% vs. 50.4%, 36.9% vs. 24%, 20.5% vs. 5.5%, respectively (χ2 = 9.997, P = 0.002). The 36.1% reduction in the hazard ratio for local-regional progression or death for D63. The MST for group D63 was 19 months (95% CI, 14.59 to 23.41) better than 15 months for group P45 (95% CI, 10.72 to 19.28), and the 1-, 2-, and 5-years OS were 70.2% vs. 52.2%, 41.3% vs. 30.7%, 16.2% vs. 11.3%, respectively (χ2 = 3.874, P = 0.049). PFS was 37% reduction in the hazard ratio for disease progression or death for D63 (χ2 = 12.49, P = 0.000). The 1, 2, 5-year LCRP of group D63 is better than group P45 (χ2 = 8.747, P = 0.003). The incidences of RE and grade Ⅲ-Ⅳ RP in group D63 were higher than in group P45 (P<0.05). Phase Ⅲ clinical trials achieved satisfactory results. LPFS, OS and PFS was longer with definitive than palliative radiotherapy of primary tumor for stage Ⅳ NSCLC with less than three metastatic organs. Significantly prolonged. The toxicity was accepted.