Novartis Builds Case for Earlier Prostate Cancer Treatment with Phase III Data

Novartis building_iStock, JHVEPhoto

Pictured: Novartis logo on its office in California/iStock, JHVEPhoto 

Novartis’ radiopharmaceutical Pluvicto (lutetium Lu 177 vipivotide tetraxetan) met its primary endpoint in the Phase III PSMAfore trial, resulting in better radiographic progression-free survival in PSMA-positive patients with metastatic castration-resistant prostate cancer, the company announced Monday.

These data, presented at the European Society for Medical Oncology Congress 2023, position Pluvicto as an earlier treatment option for these patients and could “change the treatment paradigm for advanced prostate cancer by allowing patients to potentially avoid or delay taxane-based chemotherapy,” Jeff Legos, Novartis executive vice president and global head of oncology development, said in a statement.

PSMAfore is a randomized and open-label study that enrolled 469 PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) patients who had progressed once after androgen receptor therapy. Only those who had not yet been treated with taxane-based chemotherapy were eligible for enrollment.

The trial’s primary endpoint was radiographic progression-free survival (rPFS) and found that Pluvicto treatment cut the risk of radiographic progression by 59% compared with simply switching to another androgen receptor pathway inhibitor (ARPI). Patients in the Pluvicto arm had a median rPFS of 12 months, more than double the 5.6-month duration in ARPI comparators.

At the time of the interim analysis, however, overall survival (OS) findings were “confounded” as 84% of patients who discontinued ARPI due to radiographic progression crossed over to receive Pluvicto. PSMAfore will continue to collect OS data.

Beyond survival, Pluvicto also improved patients’ quality of life, delayed the worsening of pain and induced a greater decline in prostate-specific antigen levels.

PSMAfore also assessed the safety of Pluvicto as an earlier line of treatment in this patient population and found a better profile than ARPIs. Grade 3 to 4 adverse events occurred in 33.9% of Pluvicto-treated patients compared to 43.1% of ARPIs. Serious side effects were also more common in the control arm.

However, toxicities leading to discontinuation were slightly higher in the Pluvicto arm—5.7% versus 5.2% in the ARPI group.

Pluvicto is the first FDA-approved targeted radioligand therapy, winning this regulatory designation in March 2022. The intravenous therapy uses the targeting properties of a ligand with the therapeutic action of the radionuclide lutetium-177. In the bloodstream, Pluvicto seeks out PSMA-positive prostate cancer cells to deliver the radioisotope payload, which disrupts the cells’ ability to replicate and induces cell death.

Currently, Pluvicto is indicated for PSMA-positive mCRPC patients who had been treated with an ARPI and taxane-based chemotherapy. The PSMAfore study is meant to do away with that final requirement and establish that the radioligand therapy can be given earlier in a patient’s treatment journey, potentially helping them avoid side effects associated with chemotherapy.

In December 2022, Novartis said that it was preparing to discuss a regulatory pathway for earlier-line Pluvicto treatment with the FDA but made no mention of the plans in Monday’s data drop. However, in the company’s third-quarter 2023 financial results on Tuesday, Novartis said is it is continuing to collect OS data and that regulatory filings are anticipated in 2024.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at or

Back to news