Formal discussant of the ARASENS trial, Elisabeth I. Heath, MD, FACP, Professor of Oncology and Associate Center Director, Translational Sciences, at Karmanos Cancer Institute in Detroit, commented on the changing paradigm in prostate cancer treatment. “The narrative is changing to triplet therapy, and this is important to our patients, because treatment intensification prolongs life. The reduction of death in ARASENS is encouraging. Triplet therapy is here to stay,” she stated.
Patient selection is an important consideration. “Patients with a performance status of 0–1 and those who are candidates for docetaxel plus androgen-deprivation therapy should be considered. We have tools to measure treatment toxicity to help us decide which patients can withstand treatment intensification. It is hard to argue with these numbers [for survival],” she continued.
Elisabeth I. Heath, MD, FACP
“The benefits of the triplet on secondary endpoints are also very important. Time to development of castration-resistant prostate cancer was not reached in the darolutamide arm, and this is pretty darn exciting,” Dr. Heath told listeners. “The low rates of adverse events show that the triplet is tolerable.”
“Consider the extent of disease, de novo vs recurrent disease. These patients may have different biology, but the triplet worked in both instances,” she said.
“A patient’s [prostate cancer] journey is not straightforward. I agree with Dr. Smith that we have a triplet therapy that works. We need to figure out which patients warrant this treatment. Many of our patients don’t even get a doublet. We need more education and more patient advocacy. If we have treatments, we should be offering them to patients,” she concluded.
Oliver Sartor, MD
In a separate interview, Oliver Sartor, MD, Associate Dean for Oncology and Professor at Tulane School of Medicine, New Orleans, was enthusiastic about ARASENS results. “The study was strikingly positive with an unequivocable benefit of darolutamide in patients on docetaxel and androgen-deprivation therapy. Darolutamide had an excellent side effect profile…. One question is do you really need the docetaxel? There is no question about the effect of darolutamide added to docetaxel and androgen-deprivation therapy, but would the effect be the same if darolutatmide were added to androgen-deprivation therapy without docetaxel? The trial was not designed to answer that question,” Dr. Sartor said.
Eighteen months ago, triplets were not used to treat hormone-sensitive prostate cancer. “The PEACE-1 trial showed that the triplet of androgen-deprivation therapy plus docetaxel plus abiraterone had a survival benefit, but that was restricted to high-volume disease. We don’t have data on disease volume yet in ARASENS. In my practice, I will use the triplet in relatively young patients with high-volume disease to try to maximize duration of response. We have to think about what follows, because that means using our best drugs up front to buy some time. But newer therapies are coming,” Dr. Sartor explained.
The PSMAddition trial will evaluate androgen-deprivation therapy and a second-generation hormonal therapy plus or minus lutetium-177–PSMA-617 (ClinicalTrials.gov identifier NCT04720157). That trial, if positive, will add yet another triplet to the armamentarium.
DISCLOSURE: Dr. Heath has received honoraria from Bayer, Sanofi, and Seattle Genetics; has served as a consultant or advisor to Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, and Sanofi; has served on a speakers’ bureau for Sanofi; has received institutional research funding from Agensys, AIQ Solutions, Astellas Pharma, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Calibr, Caris Life Sciences, Celgene, Celldex, Champions Oncology, Corcept Therapeutics, Curemeta, Daiichi Sankyo, Dendreon, eFFECTOR Therapeutics, Eisai, Esanik, Five Prime Therapeutics, Fortis, Genentech/Roche, GlaxoSmithKline, Ignyta, Infinity Pharmaceuticals, Inovio Pharmaceuticals, Janssen Research & Development, Medivation, Merck, Merck Sharp & Dohme, Millennium, Mirati Therapeutics, Modra Pharmaceuticals, Novartis, Oncolys BioPharma, Pellficure, Peloton Therapeutics, Pharmacyclics, Plexxikon, Seattle Genetics, Synta,Tokai Pharmaceuticals, Zenith Epigenetics, and Zenith Epigenetics. Dr. Sartor has served as a consultant or advisor to Novartis, Noria Therapeutics, Point Biopharma, Clarity, Lantheus, and Bayer.
Triplet therapy with the oral androgen receptor inhibitor darolutamide plus docetaxel plus androgen-deprivation therapy significantly improved overall survival in patients with metastatic hormone-sensitive prostate cancer vs docetaxel plus androgen-deprivation therapy, according to results of the...