2 - Initial Results of NRG Oncology NRG-GI003: A Phase III Randomized Trial of Protons vs. Photons for Hepatocellular Carcinoma (HCC)
Presenter(s)
T. S. Hong1,2, K. Winter3, E. J. Koay4, A. Kilcoyne5, J. Franses6, J. A. Wolfgang7, J. W. Sohn8, L. A. Kachnic9, D. G. Duda10, J. Y. Wo11, H. J. Roberts5, E. B. Ludmir12, S. S. Noticewala12, J. R. Kharofa13, J. K. Molitoris14, P. R. Patel15, A. Thompson16, R. Kabarriti17, K. L. Pitter18, and C. H. Crane19; 1Dana Farber Cancer Institute and Beth Israel Deaconess Medical Center, Boston, MA, 2Dana-Farber Cancer Institute, Boston, MA, 3NRG Oncology Statistics and Data Management Center, Philadelphia, PA, 4Department of Gastrointestinal Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 5Massachusetts General Hospital, Boston, MA, 6University of Chicago Comprehensive Cancer Center, Chicago, IL, 7Massachusetts General Hospital, Harvard Medical School, Boston, MA, 8Beth Israel Deaconess Medical Center, Boston, MA, 9Department of Radiation Oncology, Columbia University Irving Medical Center, New York, NY, 10Houston Methodist, Houston, TX, 11Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 12Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 13Department of Radiation Oncology, University of Cincinnati Cancer Center, Cincinnati, OH, 14Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, 15Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, 16Department of Radiation Oncology, Corewell Health William Beaumont University Hospital, Royal Oak, MI, 17Department of Radiation Oncology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, 18Memorial Sloan Kettering Cancer Center, New York, NY, 19Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
Purpose/Objective(s):
Protons may benefit patients with HCC due to favorable dose distributions and the ability to spare non-target liver. This study hypothesized that overall survival (OS) would improve with proton therapy vs photon therapy in patients with advanced HCC.Materials/Methods:
Eligible patients had pathologically or radiographically-proven unresectable or locally recurrent HCC, Zubrod performance status (PS) 0-1, Child-Pugh (CP) A or B7, 1-3 HCCs (1 HCC =15 cm, 2 HCC largest =10 cm, 3 HCC largest =6 cm) with tumor vascular thrombus (TVT) allowed if combined with a single lesion =1 cm and =15 cm. Patients were stratified by planned fractions (5 vs 15) and tumor vascular thrombosis (Yes vs No) and then randomized 1:1 to proton therapy or photon therapy given in 5 fractions (30-50 Gy) or 15 fractions (37.5-67.5 Gy) individualized based on liver-GTV mean dose. The primary endpoint was OS and secondary endpoints were progression-free survival (PFS), local progression (LP), and adverse events (AEs – CTCAEv4). An eligible sample size of 112 patients for 88 OS events provides 80% power with a 1-sided alpha=0.05 to detect the hypothesized OS hazard ratio (HR)=0.58 favoring protons, including 1 interim analysis at 63 OS events. OS was estimated by the Kaplan-Meier method and treatment arms were compared using a log-rank test.Results:
Of the 117 patients screened from June 2017 to January 2026, 116 patients were randomized and 115 eligible/analyzed: protons (n=57) and photons (n=58). Median age was 72; 93% had CP A cirrhosis; 75% had no prior treatment; 57% had single tumors, 17% 2 tumors, 3% 3 tumors, and 23% had TVT with a single lesion. At the planned interim analysis, the trial was released for reporting by the NRG Oncology Data Monitoring Committee based on the futility boundary being crossed (HR>1). Median (min-max) follow-up was 20 months (0.13-81.7). Protons did not show an improvement in OS compared to photons (1-sided p=0.83, HR=1.30, 90% CI 0.83-2.04). Univariate 24-month OS (90% CIs) was 56.2% (43.9-68.4) for protons and 69.3% (57.3-81.2) for photons. Protons did not show an improvement in PFS (2-sided p=0.92, HR=1.02, 95% CI 0.65-1.62). The 24-month PFS (95% CIs) was 31.6% (17.8-45.4) for protons and 30.4% (15.9-44.8) for photons. Protons did not show a significant improvement in LP (2-sided p=0.54, HR=0.80, 95% CI 0.36-1.77). The 24-month LP (95% CIs) was 19.8% (9.6-32.7) for protons and 22.3% (11.3-35.5) for photons. Treatment-related grade 3+ AEs were lower for the protons arm, but not significantly different (protons 11%, photons 24%; p=0.09).Conclusion:
Proton therapy did not improve OS, PFS, LP, or AEs in patients with advanced HCC. Clinical Trial Number: NCT03186898