Double VISION.

Top Line: The VISION trial was recently presented at ASCO 2021, and here is the full publication.

The Study: Prostate specific membrane antigen (PSMA) is over-expressed in many prostate cancer cells, which is associated with poor prognosis. In VISION, patients had castration-resistant prostate cancer with at least one visible metastasis on conventional imaging (mCRPC). They also had to have progressed after at least one prior androgen receptor pathway inhibitor and at least one prior taxane. Eligible patients underwent 68Ga-PSMA-11 PET/CT, and all radiographic metastases had to be PSMA-positive. Most clinically eligible patients (95%) were PSMA-positive, however 8.7% had at least one other PSMA-negative metastasis and they were ineligible for the trial. 831 patients were then randomized to receive standard of care therapy +/- Lu-177-PSMA-617. Importantly, standard therapies excluded cytotoxic chemo, other radioisotopes (Ra-223), or experimental agents. Of note, 56% of patients in the control arm withdrew during the first year of the trial prior to implementing measures to improve patient education. So, the final analysis includes 581 patients randomized after these measures. Lu-177-PSMA is a beta-emitter, and the dose was 7.4 GBq (200 mCi) every 6 weeks for 4 cycles (with the option of 2 additional cycles). As previously reported, Lu-177-PSMA improved imaging-based PFS (3.4→ 8.7 months) and overall survival (11.3→ 15.3 months). Imaging-PFS was defined by conventional imaging--not PSMA-PET. Side effects were higher with Lu-177-PSMA and mainly consisted of fatigue, dry mouth, and nausea. Ongoing trials are determining the benefit of Lu-177-PSMA as an earlier line of therapy.

TBL: The addition of Lu-177-PSMA-617 to standard therapy for PSMA-positive mCRPC progressing after an androgen receptor pathway inhibitor and a taxane significantly improves overall survival. | Sartor, N Engl J Med 2021