Heath-related quality of life, pain and safety outcomes in the phase 3 VISION study of 177Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer
Kim Chi1, Karim Fizazi2, Ken Hermann3, Bernd J. Krause4, Kambiz Rahbar5, Michael J. Morris6, Oliver Sartor7, Scott T. Tagawa8, Ayse T. Kendi9, Nicholas Vogelzang10, Jeremie Calais11, James Nagarajah12, Xiao X. Wei13, Vadim S. Koshkin, Jean-Mathieu Beauregard, Brian Chang, Michelle DeSilvio, Richard A. Messmann, Johann de Bono.
1British Columbia Cancer Agency, Vancouver Centre, Vancouver, BC, Canada; 2Gustave Roussy Institute, University of Paris Saclay, Villejuif, France; 3University Hospital Essen, Essen, Germany; 4Rostock University Medical Center, Rostock, Germany; 5University Hospital Münster, Münster, Germany; 6Memorial Sloan Kettering Cancer Center, New York, NY, United States; 7Tulane Medical School, New Orleans, LA, United States; 8Weill Cornell Medicine, New York, NY, United States; 9Mayo Clinic, Rochester, NY, United States; 10Comprehensive Cancer Centers, Las Vegas, NV, United States; 11University of California, Los Angeles, CA, United States; 12Radboud University Medical Center, Nijmegen, Netherlands; 13Dana-Farber Cancer Institute, Boston, MA, United States; 14University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, United States; 15CHU de Québec - Université Laval, Québec, QC, Canada; 16Radiation Oncology Associates, Parkview Hospital, Fort Wayne, IN, United States; 17Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States; 18The Institute of Cancer Research and Royal Marsden Hospital, London, United Kingdom
Introduction: [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) delivers β-particle radiation to prostate-specific membrane antigen (PSMA) expressing cells and the surrounding microenvironment. In the phase 3 VISION study (NCT03511664), 177Lu-PSMA-617 plus protocol-permitted standard of care (SOC) prolonged radiographic progression-free survival (rPFS; HR, 0.40; 99.2% CI: 0.29, 0.57), overall survival (OS; 0.62; 95% CI: 0.52, 0.74) and time to first symptomatic skeletal event (SSE; 0.50; 95% CI: 0.40, 0.62) versus SOC (all p < 0.001).
Methods: VISION was an international, open-label study of 177Lu-PSMA-617 in adults with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) previously treated with ≥ 1 androgen receptor pathway inhibitor and 1–2 taxane regimens. Patients were randomized 2:1 to 177Lu-PSMA-617 (7.4 GBq every 6 weeks, ≤ 6 cycles) plus SOC or to SOC alone. rPFS and OS were alternate primary endpoints; time to SSE was a key secondary endpoint. Other secondary endpoints included safety and patient-reported HRQoL (Functional Assessment of Cancer Therapy – Prostate) and pain (Brief Pain Inventory – Short Form). Prespecified analyses included time to the first occurrence of HRQoL/pain worsening, disease progression or death. Here, we present ad hoc analyses of time to worsening only (non-inferential).
Results: HRQoL was assessed in the prespecified rPFS analysis set comprising 581 of the 831 randomized patients (177Lu-PSMA-617 arm, n = 385; control arm, n = 196). HRQoL and pain time-to-worsening analyses favoured the 177Lu-PSMA-617 arm (Table 1), despite a higher incidence of grade ≥ 3 adverse events versus SOC alone. No new or unexpected safety concerns were noted, including changes in creatinine clearance.
Conclusions: 177Lu-PSMA-617 plus SOC was generally well tolerated and delayed time to HRQoL and pain worsening versus SOC alone in patients with advanced mCRPC.
