ASCO 2026 | Key prostate cancer trials at ASCO 2026: PROTEUS, TALAPRO-3, and A-DREAM

Certainly in the top two would be at the ASCO plenary session. We had the Proteus trial, which was highlighted as one of the top abstracts of the entire meeting. And the Proteus trial was over 2,000 patients that were randomized perioperatively with radical prostatectomy to 12 months of ADT, apalutamide, and ARPI or ADT alone, testing the value of treatment intensification with hormonal therapy sandwiched around the time of radical prostatectomy. The current standard of care for these patients with high-risk and very high-risk disease would be radiation, hormones, and an ARPI. So this is kind of bringing the surgeon, the urologic oncologist back into the mix and saying, can we give this in a neoadjuvant and adjuvant setting with or without adjuvant radiation and metastasis-directed therapy, pelvic radiation? And the answer is yes. The trial was positive in that this treatment-intensive approach did improve metastasis-free survival as defined by conventional and PET imaging. Pathologic complete remissions were observed in a few percent of patients. We do need to get better. We would like to see pathologic complete remissions in the 20%, 30, 50% range. So this provides a nice control basis for future trials that we’ll be looking at as add-on therapy for novel agents in this setting to build upon the success of the previous study. And now patients will have options when they have high-risk disease. They could go the radiation route or the surgical route, both of which would require ADT-ARPI therapy. The second practice-changing abstract I’d like to highlight is the TALAPRO-3 trial. Both of these trials were presented in the New England Journal of Medicine over the weekend, so readers should check those papers out. TALAPRO-3 was a metastatic hormone-sensitive prostate cancer trial that enrolled men with homologous repair deficiencies like BRCA2, ATM, CDK12, BRCA1, and randomized patients to ADT-ENZA, the ARCHES regimen, or ADT-ENZA plus talazoparib, a PARP1-2 inhibitor. And this trial was positive for its primary endpoint of delaying progression-free survival. To me, it was surprising that it was a positive study, both in all comers, particularly in BRCA patients, but also was very positive in patients with ATM and CDK12 mutations. So for me, that was practice-changing and illustrates that in the hormone-sensitive setting, there can be multiple homologous repair alterations that confer PARP sensitivity. Overall survival is still immature, but a favorable trend, and adverse events are particularly anemia. So about 40%, 45% of patients did require a transfusion, particularly in the first few months, and dose reduction to get patients through. Two other abstracts I’d like to highlight was Atish Chowdhury’s trial called ADREAM, which was a small phase two study testing the value of treatment deintensification of ADT-RPs in patients who have a PSA that’s undetectable in the metastatic setting. So ADT-RP is standard of care, but the current standard of care is to continue this treatment until progression, which can be many, many years. And after about two years, if your PSA is undetectable, many men wonder, can they take a treatment break and come off therapy? And Dr. Chowdhury illustrated that the answer is yes, that you can safely come off this therapy. And somewhere around 30% to 40% of patients can remain off therapy with testosterone recovery a year and a half to two years later. And so intermittent ADT-ARPI therapy should be something to test in phase three studies, number one, but also in patients who are having a lot of side effects from ADT-ARPI and having a complete remission, giving brief treatment breaks can really improve quality of life and comorbidities. And certainly shared decision-making around that is really critical. Of course, like the EMBARK study, you would probably need to go back on ADT-ARPI and following those patients carefully. Integrating metastasis-directed therapy may help extend that break, but really kind of changing the paradigm of continuous back to considerations of intermittent therapy for selected patients who are really ultra-responders. Another trial that was an interventional trial that I’d like to highlight was Dr. Dorff’s trial of the AbbVie antibody drug conjugate. And this is a really novel ADC that uses a topo one inhibitor to target two cell surface molecules, PSMA and STEAP1. And, you know, this was in the rapid oral abstract session, only got about six minutes of time, but really was exciting to me because the objective response rate was very high. And the progression-free survival was very impressive at around 15 months with very acceptable toxicity in a very heavily pretreated patient population. So I think this is a, you know, a very nice antibody drug conjugate, perhaps the best in its class that I have seen. And I think it should be tested in phase three and is really exciting for patients who have exhausted other treatment options.

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