273 - A Prospective, Randomized Controlled Study on the Time Window of Radiotherapy Combined with Targeted Therapy for Primary Tumor in Stage IV NSCLC
Presenter(s)
C. Hu1, Q. Li2,3, W. Ouyang4, Z. Ma5, W. Yang6, X. Chen7, H. Li8, Y. Hu2, S. Su9, B. Lu2, and F. Jin10; 1Guizhou Medical University, Guiyang, Guizhou, China, 2Department of Oncology, The Affiliated Hospital of Guizhou Medical University,and the Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, Guizhou, China, 3Affiliated Hospital of Guiyang Medical University and Guizhou Cancer Hospital, Guiyang, China, 4Department of Oncology, Affiliated Hospital of Guizhou Medical University,and Affiliated cancer Hospital of Guizhou Medical University., Guiyang, Guizhou, China, 5Department of Oncology, Affiliated cancer Hospital of Guizhou Medical University, Guiyang, China, 6Department of Oncology, Affiliated Hospital of Guizhou Medical University, and Guizhou Cancer Hospital, Guiyang, China, 7Department of Oncology, Affiliated Hospital of Guizhou Medical University,and Affiliated cancer Hospital of Guizhou Medical University., Guiyang, China, 8Department of Thoracic Oncology, Affiliated Hospital of Guizhou Medical University, and Guizhou Cancer Hospital, Guiyang, PR China;Teaching and Research Section of Oncology, Guizhou Medical University, Guiyang, PR China, Guiyang, China, 9Guizhou Cancer Hospital, Guiyang, Guizhou, China, 10Department of Oncology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
Purpose/Objective(s): To conduct a prospective, multicenter, randomized controlled clinical trial to find the appropriate radiotherapy time window for primary tumor radiotherapy combined with molecular targeted therapy in stage IV non-small cell lung cancer (NSCLC).
Materials/Methods: This equivalence design trial calculated the sample size based on an assumed objective response rate of 70%. With a power (1-ß) of 0.80 and a 1:1 randomization ratio, and accounting for a 10% dropout rate, the required sample size was determined to be 160 patients. Patients were assigned to Group A (concurrent radiotherapy group, with radiotherapy initiated within one week of starting TKI therapy) or Group B (radiotherapy group, with radiotherapy initiated 40-47 days after starting TKI therapy) in a 1:1 ratio. All statistical tests were two-sided, and a P-value = 0.05 was considered statistically significant. Survival data were analyzed using Kaplan-Meier curves with the log-rank test and Cox regression models to compare overall survival and treatment toxicity between the two groups.
Results:
From January 2020 to July 2025, 160 patients were enrolled (80 in Group A, with an EGFR mutation rate of 87.5%; 80 in Group B, with an EGFR mutation rate of 82.5%). There were 15 dropouts (9 in Group A and 6 in Group B). The last follow-up date was December 2025. The median follow-up time was 30 months (range, 5-64 months), and one patient was lost to follow-up. The median progression-free survival (PFS) times for Groups A and B were 16 months and 23 months, respectively. The 1-, 2-, and 3-year PFS rates were 61.0% vs. 67.6%, 26.2% vs. 42.1%, and 8.7% vs. 37.4%, respectively (?²=6.380, P=0.012). The median overall survival (OS) times for Groups A and B were 23 months and 27 months, respectively. The 1-, 2-, and 3-year OS rates were 69.8% vs. 70.3%, 46.7% vs. 51.6%, and 25.8% vs. 35.6%, respectively (?²=0.389, P=0.533). The incidence of the most common TKIs-related adverse events, rash and gastrointestinal reactions, did not differ significantly between the two groups when all patients were included in the drug-related adverse event analysis. Regarding radiotherapy-related toxicities, no fatal adverse events occurred in either group. The incidence of grade I-II radiation pneumonitis (RP) in Groups A and B was 23.7% and 12.7%, respectively, and the incidence of grade III-IV RP was 11.8% and 4.2% (?²=6.764, P=0.034). No significant differences were observed between the two groups in the incidence of radiation esophagitis, leukopenia, neutropenia, thrombocytopenia, or anemia.Conclusion: The results of this prospective, randomized controlled trial on the timing window of primary tumor radiotherapy combined with targeted therapy for stage IV NSCLC suggest that initiating primary tumor radiotherapy 40-47 days after the start of molecular targeted therapy can result in greater radiation field shrinkage, lead to longer progression-free survival (PFS), and reduce the incidence of radiation pneumonitis (RP).