CALGB 90206 was a phase III trial of 732 mRCC patients comparing bevacizumab plus interferon alpha (BEV+IFN) versus interferon alpha alone (IFN). No difference in overall survival (OS) was observed. Baseline samples were analyzed to identify predictive biomarkers for survival benefit.
A total of 32 biomarkers were assessed in 498 patients randomly assigned into training (n=279) and testing (n=219) sets. The proportional hazards model was used to test for treatment arm and biomarker interactions of OS. The estimated coefficients from the training set were used to compute a risk score for each patient and to classify patients by risk in the testing set. The resulting model was assessed for predictive accuracy using the time-dependent area under the receiver operating characteristic curve (tAUROC).
A statistically significant 3-way interaction between IL-6, HGF, and bevacizumab treatment was observed in the training set and confirmed in the testing set (p<0.0001). The model based on IL-6, HGF and bevacizumab treatment was predictive of OS (p<0.001) with the high and low risk groups having a median OS of 10.2 (95% CI=8.0-13.8) and 34.3 (95% CI 28.5-40.5) months, respectively. The average tAUROC for the final model of OS based on 100 randomly split testing sets was 0.78 (1st, 3rd quartiles=0.77, 0.79).
IL-6 and HGF are potential predictive biomarkers of OS benefit from BEV+IFN in mRCC patients. The model based on key biological and clinical factors demonstrated predictive efficacy for OS. These markers warrant further validation in future anti-VEGF and immunotherapy in mRCC trials.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2021 Dec 29 [Epub ahead of print]
Andrew B Nixon, Susan Halabi, Yingmiao Liu, Mark D Starr, John C Brady, Ivo Shterev, Bin Luo, Herbert I Hurwitz, Phillip G Febbo, Brian I Rini, Himisha Beltran, Eric J Small, Michael J Morris, Daniel J George
Medicine, Duke Medical Center ., Biostatistics and Bioinformatics, Duke Medical Center., Medicine, Duke Medical Center., Biostatistics and Bioinformatics, Duke University., Biostatistics and bioinformatics, DUMC., Oncology Development, Genentech., Medicine and Urology, UCSF Helen Diller Family Comprehensive Cancer Center., Hematology/Oncology, Vanderbilt University., Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School., Medical Oncology, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco., Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College., Departments of Medicine and Surgery, Duke University, Duke Cancer Institute.