Philip Kantoff, MD

PHILIP KANTOFF, MD, of Memorial Sloan Kettering Cancer Center, New York, was the formal discussant of both trials. “At first glance, these are two positive trials,” Dr. Kantoff said. Although he praised the results, he said that overall survival is the best demonstration of clinical benefit, and for both trials, it is too early to tell whether either drug improved overall survival in the nonmetastatic setting.

“Telling asymptomatic patients to be treated carries a burden of proof where benefits outweigh the risk,” Dr. Kantoff stated. “Without demonstration of an overall survival benefit, clinical benefit needs to be demonstrated.”

“Probably the strongest evidence we have yet is that apalutamide delayed the time to symptomatic progression. This provides a hint of clinical benefit,” continued Dr. Kantoff. “The crude instruments used to assess quality of life do not capture the psychological benefit of a decline in prostate-specific antigen (PSA) or a delay in symptom progression on quality of life. The incidence of grade 3 and 4 toxicities (rash, falls, and fractures) in the SPARTAN trial, although low, is important. And in the PROSPER trial, 15% in the enzalutamide (Xtandi) arm died within 3 months of stopping enzalutamide treatment. This is concerning; we need to dissect this further. “My confidence would be greater with further scrutiny of toxicities and understanding of patterns of care with regard to alternative therapies in the community,” he said.

“The data are very interesting. Apalutamide and enzalutamide delay metastasis-free survival in men with nonmetastatic castrate-resistant prostate cancer for an impressive 2 years. The drugs are biologically active and are potential new options for men with this type of cancer,” Dr. Kantoff stated.

“Once again, treating asymptomatic patients carries a burden of proof where benefits must outweigh the risks,” he continued. “We need to watch closely how these agents are used in the real-world setting.”

Additional Commentary 

ASCO EXPERT Sumanta Pal, MD, of City of Hope, said, “There are remarkable parallels between the magnitude of benefit in these two trials and in the performance of the study arms and placebo arms.”

When asked whether the recent (Feburary 14) U.S. Food and Drug Administration approval of apalutamide in this patient population would lead to greater use of this agent (if compared with enzalutamide), Dr. Pal replied: “Apalutamide faces an uphill battle. Many of us in the oncology community are comfortable with enzalutamide. There is no rhyme or reason to move to an agent we have no experience with.”

Dr. Pal agreed with Dr. Kantoff. “The bar is high. We need to demonstrate a clinical benefit in patients who are asymptomatic and free of metastatic disease. Patients do fear the development of metastasis, but we don’t have improvement in overall survival yet,” Dr. Pal noted. ■

DISCLOSURE: Dr. Kantoff has been a consultant for BN Immunotherapeutics, Genentech/Roche, Janssen, Merck, and Sanofi. Dr. Pal reported no conflicts of interest.