The rate of tumor growth, g, as a biomarker for overall survival (OS) in prostate cancer (PC) in clinical trials as well as in real-world data from the Veterans Administration Medical Centers (VAMCs).

person Harshraj Leuva James J Peters VAMC, Bronx, NY info_outline Harshraj Leuva, Mengxi Zhou, Julia Wilkerson, Keith Sigel, Ta-Chueh Hsu, David Henry Aggen, Erik Langhoff, Yeun-Hee Anna Park, Susan Elaine Bates, Antonio Tito Fojo

Authors person Harshraj Leuva James J Peters VAMC, Bronx, NY info_outline Harshraj Leuva, Mengxi Zhou, Julia Wilkerson, Keith Sigel, Ta-Chueh Hsu, David Henry Aggen, Erik Langhoff, Yeun-Hee Anna Park, Susan Elaine Bates, Antonio Tito Fojo Organizations James J Peters VAMC, Bronx, NY, Columbia University, NY, NY, Mount Sinai School of Medicine, New York, NY, James J Peters VAMC, New York, NY, Columbia University Medical Center, New York, NY, James Peters Bronx Veterans Affairs Medical Center, Bronx, NY, New York Presbyterian - Columbia, New York, NY, James J. Peters Bronx VA Medical Center, Bronx, NY Abstract Disclosures Research Funding Other Background: Novel assessments of efficacy are needed to improve determination of treatment outcomes in clinical trials and in real-world settings. Methods: Cancer treatments usually lead to concurrent regression and growth of the drug-sensitive and drug-resistant fractions of a tumor, respectively. We have exploited novel methods of analysis that assess these two simultaneous processes and have estimated rates of tumor growth ( g ) and regression ( d ) in over 30,000 patients (pts) with diverse tumors. Results: In prostate cancer (PC) we have analyzed both clinical trial and real-world data from Veterans. Using clinical trial data from 6819 pts enrolled in 15 treatment arms we have established separately and by combining all the data that g correlates highly (p<0.0001) with overall survival (OS) – slower g associated with better OS. In PC, abiraterone (ABI) and docetaxel (DOC) are superior to placebo, prednisone and mitoxantrone. ABI (median g =0.0017) is superior to DOC ( g =0.0021) in first line (p=0.0013); and ABI in 2 nd line ( g =0.0034) is inferior to ABI in 1 st line ( g =0.0017; p<0.0001). Finally, using combined clinical trial data as a benchmark we could assess the efficacy of novel therapies in as few as 30-40 patients. Amongst 7457 Veterans, the median g on a taxane ( g =0.0022) was similar to that from clinical trials ( g =0.0012). Although only 258 Veterans received cabazitaxel (CAB), g values for CAB ( g =0.0018) and DOC ( g =0.0023) were indistinguishable (p=0.3) consistent with their identical mechanism of action. Finally, outcomes with DOC in African American (AA) ( g =0.00212) and Caucasian ( g =0.00205) Veterans were indistinguishable (p=0.9) and comparable across all VAMCs. Conclusions: The rate of tumor growth, g , is an excellent biomarker for OS both in clinical trials and in real-world settings. g allows comparisons between trials and for large trial data sets to be used as benchmarks of efficacy. Real-world outcomes in the VAMCs are similar to those in clinical trials. In the egalitarian VAMCs DOC efficacy in PC is comparable in AA and Caucasian Veterans -- indicating inferior outcomes reported in AAs are likely due to differential health care access, not differences in biology.