Study discussant Dana E. Rathkopf, MD, Director of Clinical Research, Prostate Cancer, at Memorial Sloan Kettering Cancer Center, New York, began her presentation by noting that the “complicated” landscape of metastatic prostate cancer can be approached like a chess game. She used a chess analogy to suggest treatment decisions: “Know the pieces—where do they go? Watch your back—always look at all your possibilities. Don’t play too fast—if you see a good move, look for a better one. There are many good options, and probably more than one for each patient.”

Dana E. Rathkopf, MD

Turning to Dr. Agarwal’s presentation, Dr. Rathkopf noted that the results clearly show that the endpoint of second disease progression or death (PFS2) is superior with apalutamide in men with metastatic castration-sensitive prostate cancer in this trial. However, she said that the small number of PFS2 events in the hormonal arm (19.5%) and the taxane arm (22.4%) “should be interpreted with some caution. Further follow-up is needed to assess the full impact of subsequent therapy on time to PFS2,” Dr. Rathkopf said.

The duration of first therapy after apalutamide or placebo was not quite 12 months in each study arm. The requirement to have a second disease progression meant that the study selected for poor responders who were on treatment for less than 24 months, she pointed out.

“If the patients were all on their second treatment for about 12 months, it does make you wonder why patients who received apalutamide responded better than patients who received placebo to a second hormone therapy, because you might think that in the setting of poor response to upfront apalutamide, these patients may develop some type of intrinsic resistance that would suggest they would not respond as well to a second-line androgen receptor inhibitor relative to a taxane,” Dr. Rathkopf elaborated.

Additionally, the higher number of patients in the apalutamide arm who received prior docetaxel therapy (33% vs 16% in the control arm) also could have influenced outcomes, she suggested.

DISCLOSURE: TITAN was funded by Janssen Research and Development. Dr. Rathkopf has served in a consulting or advisory role for AstraZeneca, Bayer, Genentech, and Janssen and has received institutional research funding from AstraZeneca, Celgene, Ferring, Genentech/Roche, Janssen Oncology, Medivation, Millennium, Novartis, Taiho Pharmaceutical, Takeda, and TRACON Pharma.