European Commission Approves Pluvicto for PSMA-Positive mCRPC

The European Commission has approved lutetium Lu 177 vipivotide tetraxetan (Pluvicto; formerly ¹⁷⁷Lu-PSMA-617) in combination with androgen deprivation therapy (ADT) with or without androgen receptor (AR) pathway inhibition, for the treatment of adult patients with prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with AR pathway inhibition and taxane-based chemotherapy.¹

The approval follows a positive opinion issued in October by the European Medicines Agency’s Committee for Medicinal Products for Human Use and is applicable to all 27 European Union member states plus Iceland, Norway, Northern Ireland, and Liechtenstein.²

The approval was granted based on findings from the pivotal phase 3 VISION trial (NCT03511664), in which Pluvicto plus best standard of care led to a 38% reduction in the risk of death and a statistically significant reduction (60%) in the risk of radiographic disease progression or death (rPFS) vs best standard of care alone in patients who were previously treated with AR pathway inhibition and taxane-based chemotherapy.

Additionally, 30% of patients with evaluable disease at baseline achieved an objective response per RECIST v1.1 criteria with the combination regimen compared with the 2% in the best standard of care alone arm.

“Today’s approval of Pluvicto by the European Commission marks a major milestone for patients with advanced prostate cancer who have few alternative treatments at this stage of their disease,” Haseeb Ahmad, president Europe, Novartis, said in a press release. “We are excited by the potential of Pluvicto to bring groundbreaking clinical benefits to these patients, transforming cancer care for the third-most diagnosed cancer globally.”

On March 23, 2022, the FDA approved Lu 177 vipivotide tetraxetan for the treatment of adult patients with PSMA-positive mCRPC who have previously received AR pathway inhibition and taxane-based chemotherapy, also based on findings from the VISION trial.³

To be eligible for enrollment in the study, patients had to have received a diagnosis of CRPC with at least 1 metastatic lesion and progressed following prior treatment with at least 1 AR pathway inhibitor and 1 or 2 taxane regimens.⁴ Patients also needed to have at least 1 PSMA-positive metastatic lesion and no PSMA-negative lesions that would be excluded according to protocol criteria. An ECOG performance status between 0 and 2, a life expectancy of at least 6 months, and adequate bone marrow and organ function were also required.

Enrolled patients were randomly assigned 2:1 to receive 7.4 GBq (200 mCi) of lutetium Lu 177 vipivotide tetraxetan once every 6 weeks for 4 cycles plus best standard of care or best standard of care alone. If patients in the experimental arm had evidence of response, they were permitted to receive 2 additional cycles of the radioligand therapy, per investigator discretion.

rPFS and overall survival (OS) served as the co-primary end points of the study. Secondary end points included objective response rate, disease control rate, time to first symptomatic skeletal event, safety, health-related quality of life, pain, and biomarker outcomes.

Additional efficacy data showed that at a median follow-up of 20.9 months, the median rPFS with Pluvicto was 8.7 months vs 3.4 months with best standard of care alone (HR, 0.40; 99.2% CI, 0.29-0.57; P < .001). Moreover, the median OS with Pluvicto was 15.3 months vs 11.3 months with best standard of care alone (HR, 0.62; 95% CI, 0.52-0.74; P < .001).

Regarding safety, the most frequent any-grade adverse effects in the Pluvicto arm included fatigue (43.1%), dry mouth (38.8%), nausea (35.3%), anemia (31.8%), back pain (23.4%), arthralgia (22.3%), decreased appetite (21.2%), and constipation (20.2%).

References

1. Novartis receives European Commission approval for Pluvicto as first targeted radioligand therapy for treatment of progressive Psma-positive metastatic castration-resistant prostate cancer. News release. Novartis. December 13, 2022. Accessed December 13, 2022. https://bit.ly/3FKnSll
2. Novartis receives positive CHMP opinion for Pluvicto® for patients with progressive, PSMA-positive metastatic castration-resistant prostate cancer. News release. Novartis. October 14, 2022. Accessed December 13, 2022. https://bit.ly/3Td7jDA
3. FDA approves Pluvicto for metastatic castration-resistant prostate cancer. News release. FDA. March 23, 2022. Accessed December 13, 2022. https://bit.ly/3LaWA8w
4. Sartor O, de Bono J, Chi KN, 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