Eric Huttenlocher Bent, MD, PhD, on Oligometastatic Prostate Cancer: Intensified Hormonal Blockade

Here at ASCO, we presented on cohorts B2 and the B2 expansion of the MEDCARE trial. This trial looked at intensified hormonal blockade in combination with metastasis-directed radiation in patients with oligometastatic castration-sensitive prostate cancer. We know that in patients with oligometastatic prostate cancer, radiation directed to metastases either with or without hormonal therapy is a widely used treatment approach. We also know that in patients with metastatic hormone-sensitive prostate cancer, intensification of hormonal therapy with an ARSI in addition to ADT improves overall survival in multiple large phase 3 randomized trials. What is less certain at this point in time is what the appropriate intensity and duration of hormonal blockade is in patients who are getting metastasis-directed radiation for low-volume oligometastatic hormone-sensitive prostate cancer. ADT and apalutamide—one of the treatment regimens tested on this protocol—is a standard treatment approach for patients with mHSPC. In this context, the MEDCARE trial was designed, which is a multi-cohort, multi-center randomized phase 2 trial that treated patients with either hormonal doublet therapy (ADT and apalutamide) or triplet hormonal therapy (ADT, apalutamide, and abiraterone) in combination with radiation and/or surgery for patients who have an intact primary tumor. We presented on cohorts B2 and the B2 expansion. These enrolled patients with metachronous oligometastatic prostate cancer—so prostate cancer that had recurred after initial treatment to the primary tumor. Patients had to have had a prior radical prostatectomy, a PSA that rose to greater than 0.2, and PET-detected lymph node or bone metastatic disease. All patients got conventional imaging in addition to PET-based imaging approaches. Patients had to have disease treatable on a maximum of three radiation plans. The primary endpoint for this trial was the proportion of patients with an undetectable PSA at 12 months from treatment initiation, with the goal of getting an early readout of treatment efficacy. Patients meeting that primary endpoint also had to have recovered testosterone to greater than 150. The primary endpoint was met by a total of 11 of 26 patients on the B2 expansion cohort (43%) and 5 of 10 patients in the combined B2 cohorts. This trial enrolled patients, the majority of whom had conventional imaging-detected metastases—that was seen in 75% of patients—and 75% of patients had a single metastatic lesion irradiated. The median PSA at enrollment on the trial was 1.2. We also saw durability of this treatment approach. At 24 months from treatment initiation, 60% of patients across treatment arms had not yet had a PSA recurrence—and that’s despite a very stringent definition of PSA recurrence on the trial: just greater than 0.2. Additionally, when we looked at individual patient response, 16 of the 36 patients on the trial had not yet had a PSA recurrence or any recurrence event despite recovered testosterone and completing either three years of follow-up on trial or who remained on study follow-up. Median follow-up for those 16 patients was well over 2 years. Treatment was very well tolerated on this protocol. There was one grade 3 lymphopenia event, and otherwise side effects were in line with what we would expect with these well-tolerated treatment regimens. So in conclusion, I think that metastasis-directed radiation with short but intensified hormonal blockade is a very promising approach for the management of patients with oligometastatic prostate cancer.