FDA Approves Lu 177 Vipivotide Tetraxetan for Metastatic Castration-Resistant Prostate Cancer

The FDA has granted approval to the agent formerly known as 177Lu-PSMA-617 for the treatment of patients with metastatic castration-resistant prostate cancer in the post androgen receptor pathway inhibition, post-taxane-based chemotherapy setting.

The FDA has granted approval to Lu 177 vipivotide tetraxetan (Pluvicto; formerly 177Lu-PSMA-617), for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) in the post androgen receptor pathway inhibition, post-taxane-based chemotherapy setting, according to a press release issued by Novartis.1

"The first availability of tumor-targeted radionuclide therapy on a commercial basis will allow patients with more limited resources that might not have been able to travel for a clinical trial or overseas to receive the benefit of this treatment. The first successful phase 3 trial allows us in research to optimize the treatment, study it in earlier disease states, and explore combinations with other therapies with scientific merit. Even after this approval, I encourage clinical trial participation and/or referrals, said Scott Tagawa, MD, MS, FACP, professor of Medicine and Urology at Weil Cornell Medicine, attending physician at NewYork Presbyterin, and co-investigator of the VISION study, in an interview with Targeted OncologyTM.

The decision to approve Lu 177 vipivotide tetraxetan was supported by findings from an international, prospective, open-label, multicenter, randomized, phase 3 study (VISION; NCT03511664).In VISION, treatment with Lu 177 vipivotide tetraxetan combined with standard of care (SOC) therapy demonstrated significant improvement in overall survival (OC) as well as radiographic progression-free survival (PFS) compared with SOC alone in patients with prostate-specific maturation antigen (PSMA)-positive mCRPC.

"PSMA-targeted radiation is safe and leads to clinically meaningful improvements in delaying cancer progression and death in patients with few other options," saidTagawa stated about the study.

Patients in the study were randomized patients 2:1 to received either Lu 177 vipivotide tetraxetan at 7.4 GBq (+/- 10%) intravenously every 6 weeks for up to 6 cycles with SOC or the best SOC alone. A total of 831 patients were included and assessed for the coprimary end points of OS and rPFS. The secondary end point of the study was the number of patients with treatment-emergent adverse events (TEAEs).2

At a median follow-up of 20.9 months, the median OS observed in the Lu 177 vipivotide tetraxetan plus SOC arm was 15.3 months compared with 11.3 months in the SOC-alone arm (HR, 0.61; 95% CI, 0.52-0.74; P <.0001). In terms of rPFS, the median observed with Lu 177 vipivotide tetraxetan plus SOC was 8.7 months versus 3.4 months with SOC alone (HR, 0.40; 99.2% CI, 0.29-0.57; P <.001). The results for all the secondary efficacy end points favored the Lu 177 vipivotide tetraxetan combination as well.

The safety of 1Lu 177 vipivotide tetraxetan in the VISION study appeared consistent with its profile in earlier analyses. Patients were exposed to the drug for a median of 6.9 months (range, 0.3-10.2). Any-grade AEs were seen in 98.1% of patients in the combination arm compared with 82.9% in the SOC arm. The most frequent AEs observed with the experimental combination were fatigue (43.1%), dry mouth (38.8%), and nausea (35.3%). Fatigue and nausea were also commonly observed in the SOC arm at 22.9% and 16.6%, respectively.

"I expect initial use to be limited to those patients which have had most of the other available treatments. Initial practical limitations might be getting access to PSMA PET imaging and finding a facility that has the capability of administering Lu 177 vipivotide tetraxetan. For individual patients that need treatment soon, it may be worth traveling for imaging and/or the first 1-2 cycles of therapy to give their local provider/system time to get the process up and running, then continue subsequent cycles closer to home, Tagawa said. "Practitioners that lack experience might ask those with experience with at referral centers and also might ask GI oncology colleagues who might have experience with 177Lu-dotatate - though there are some differences in efficacy/safety based upon different disease/target, some practical information about overall experience and the referral process might be useful".


1 Novartis PluvictoTM approved by FDA as first targeted radioligand therapy for treatment of progressive, PSMA positive metastatic castration-resistant prostate cancer. News release. Novartis. March 23, 2022. Accessed March 23, 2022. https://bit.ly/3iw9bab

2. Sartor O, de Bono J, Chi Km, et al. Lutetium-177–PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021; 385(12):1091-1103. doi: 10.1056/NEJMoa2107322