Pluvicto Receives UK Approval for Earlier Use; Meta-Analysis Confirms PFS Benefit

Novartis announced that Pluvicto (lutetium-177 vipivotide tetraxetan) has received MHRA approval for a new indication for adult patients with prostate specific membrane antigen (PSMA)–positive metastatic castration resistant prostate cancer (mCRPC) who have progressed on or after androgen receptor pathway inhibitor (ARPI) therapy and are considered appropriate to delay taxane based chemotherapy. This approval means that lutetium-177 vipivotide tetraxetan can now be administered to eligible patients earlier in the treatment pathway.

The MHRA approval is based on Phase III PSMAfore clinical trial results demonstrating a statistically significant improvement in radiographic progression free survival, with a 59% reduction in risk of radiographic progression or death vs ARPI change (hazard ratio [HR] 0·41 [95% CI 0·29–0·56]; p<0·0001). In the study lutetium-177 vipivotide tetraxetan extended the median time to disease progression or death vs ARPI change by 3.7 months (9.3 vs. 5.6 months respectively) HR 0.41; 95% CI: 0.29, 0.56; p<0.0001) compared to a change in ARPI in patients with PSMA-positive mCRPC after treatment with ARPI therapy.

In the PSMAfore Trial, the median overall survival (OS) was 24.48 months (95% CI 19.55-28.94 months) with 177Lu-PSMA-617 and 23.13 months (19.61-25.53 months) with ARPI change (HR 0.91, 95% CI 0.72-1.14, P = 0.20) based on the intended to treat (ITT) principle. The OS analysis was confounded by the high rate of patients who crossed over from the control arm to Pluvicto (60.3%). When adjusted for crossover, the OS hazard ratio was 0.59 (95% CI: 0.38, 0.91) with the inverse probability of censoring weighting (IPCW) method. The key secondary endpoint of overall survival did not achieve statistical significance.

Additional findings from the PSMAfore trial showed lutetium-177 vipivotide tetraxetan demonstrated an acceptable safety profile. The most frequently reported all-grade adverse events for Pluvicto were primarily Grade 1-2 and included dry mouth (58%), fatigue (23%), nausea (32%), and constipation (22%). Lutetium-177 vipivotide tetraxetan did not impair the ability of patients to be treated with subsequent chemotherapy.

A pooled analysis presented at the inaugural Multidisciplinary Radiopharmaceutical Therapy Symposium, presented by the American Society for Radiation Oncology (ASTRO) in Palm Desert, California, evaluated data from 2526 patients who took part in 7 randomized trials; 1365 were enrolled in Lu-177 PSMA-617 arms and 1161 were enrolled in standard-of-care arms. Findings showed improved PFS compared with control, for a pooled HR of 0.64 (95% CI, 0.50–0.81; P < .001).

The analysis found no significant difference in overall survival (OS) between the 2 arms (HR = 0.91; 95% CI 0.66–1.25; P = 0.55). Patients receiving radioligand therapy did not experience a significant increase in serious adverse events (AEs). The pooled risk ratio for AEs of grade 3 or higher was 0.98 (95% CI 0.83–1.14; P = 0.75).

According to Prostate Cancer UK latest research 64,425 people were diagnosed with the disease in 2022, making prostate cancer the most common cancer in the UK. Some diagnosed patients may eventually progress to mCRPC once the disease spreads and no longer responds to androgen deprivation therapy. Although hormone therapies and chemotherapy are available treatment options in the UK, they may not be appropriate for all, and many patients and their healthcare providers may consider avoiding or delaying chemotherapy.

In cancer care, radioligand therapy combines a radioisotope with a ligand, which binds the agent to markers on specific cancer cells. In the case of Pluvicto, the radioactive isotope Lutetium-177 (Lu 177) is deployed to target radiation directly to cancer cells; it is delivered by intravenous infusion every 6 weeks.