LBA 04 - A Double-Blinded Placebo-Controlled Biomarker Stratified Randomized Trial of Apalutamide (APA) and Radiotherapy for Recurrent Prostate Cancer (NRG GU006, BALANCE trial)

01:00pm - 01:10pm PT

San Francisco Ballroom

Presenter(s)

Daniel Spratt, MD - University Hospitals Seidman Cancer Center, Case Western Reserve University, Beachwood, OH

D. E. Spratt¹, T. G. Karrison², H. M. Sandler³, E. Posadas³, R. C. Chen⁴, R. E. Wallace³, J. I. Monroe⁵, L. G. Gomella⁶, R. T. Dess⁷, A. D. Vassil⁸, A. Ebacher⁹, T. Gunter¹⁰, R. J. Lee¹¹, J. W. DiNome¹², S. E. Delacroix Jr¹³, J. M. Michalski¹⁴, X. Shen⁴, T. Johnson¹⁵, P. L. Nguyen¹⁶, and F. Y. Feng¹⁷; ¹Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, ²NRG Oncology SDMC, Philadelphia, PA, ³Cedars-Sinai Medical Center, Los Angeles, CA, ⁴Department of Radiation Oncology, University of Kansas Medical Center, Kansas City, KS, ⁵St. Anthony's Cancer Center, St. Louis, MO, ⁶Department of Urology, Sidney Kimmel Cancer Center of Thomas Jefferson University, Philadelphia, PA, ⁷Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, ⁸Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, ⁹CHUS, Albacete, Spain, ¹⁰University of Oklahoma Health Sciences Center, Oklahoma City, OK, ¹¹Intermountain Medical Center, Murray, UT, ¹²Department of Radiation Oncology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, ¹³Mary Bird Perkins Cancer Center and Gulf South NCORP, Metairie, LA, ¹⁴Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, ¹⁵American College of Radiology, Philadelphia, PA, ¹⁶Department of Radiation Oncology, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, MA, ¹⁷UCSF, San Fransisco, CA

Purpose/Objective(s):

Currently there are no prospectively validated predictive biomarkers to guide use of hormonal therapy in prostate cancer. NRG GU006, a phase II biomarker stratified randomized trial of patients receiving salvage radiotherapy (SRT) with or without APA, was designed with the hypothesis that transcriptionally defined molecular subtypes would differentially benefit from APA.

Materials/Methods:

Patients were enrolled between 4/2018-2/2020 and were required to be status post-radical prostatectomy with a PSA 0.1-1.0 ng/mL without evidence of nodal or distant metastasis and randomized to SRT with placebo or APA 240 mg daily for 6 months. Patients were stratified by PAM50 molecular subtype (luminal B vs non-luminal-B). The primary endpoint was biochemical progression-free survival (bPFS), defined as first occurrence of biochemical, local, regional, distant recurrence, or death from any cause. Key secondary endpoints reported are metastasis-free survival (MFS) and adverse events. The design and analysis involved first testing efficacy within the luminal B subtype (hypothesized to show greater benefit), followed by evaluation of the non-luminal-B group. If the lower limit of the 80% confidence interval (CI) for the hazard ratio (HR [APA/placebo]) in the latter group was >0.77, lack of efficacy in this subgroup would be declared.

Results:

A total of 295 eligible patients were enrolled with a median follow-up of 5.0 years. Arms were well balanced, with a median age of 65 years, 50% with positive surgical margins, 51% with pathologic T3 disease, 86% with entry PSA of <0.5 ng/mL; 19% were grade group 4-5, and 43% were luminal B. In luminal B patients APA significantly improved bPFS (HR 0.45, 80%CI 0.29-0.68, one-sided p=0.0062), with 5-year estimated bPFS of 72.4% vs 53.9% in the APA and placebo arms, respectively. In contrast, non-luminal B patients did not demonstrate improvement in bPFS (HR 0.95, 80%CI 0.65-1.41, p=0.44), with 5-year estimated bPFS of 70.2% vs 71.1%, although the lower CI limit was <0.77. MFS was also improved with APA in luminal B patients, HR 0.27, 95%CI 0.07-0.95, p=0.029; 5-year estimates of 94.7% vs 81.8%, but not in non-luminal B patients, HR 1.06, 95%CI 0.41-2.78, p=0.90; 5-year estimates of 89.9% vs 89.3%. In the APA vs placebo arm (regardless of attribution), grade 3+ gastrointestinal toxicity occurred in 5.7% vs 2.6%, and genitourinary toxicity in 3.5% vs 4.5%, respectively. In the APA arm, grade 3+ rash occurred in 5.0% of patients and breast pain in 0.7%.

Conclusion:

Patients with transcriptionally defined luminal B tumors derived improvement in clinically meaningful endpoints from the addition of APA to SRT. PAM50 represents the first prospectively validated predictive biomarker for hormone therapy in prostate cancer in a randomized trial.