Novartis Builds Case for Earlier Prostate Cancer Treatment with Phase III Data. Pluvicto from Novartis fulfilled its Phase III PSMAfore study’s primary endpoint, improving radiographic progression. The company revealed free survival in PSMA-positive metastatic castration-resistant prostate cancer patients on Monday.
Novartis executive vice president and global head of oncology development Jeff Legos said these data at the European Society for Medical Oncology Congress 2023 could “change the treatment paradigm for advanced prostate cancer by allowing patients to avoid or delay taxane-based chemotherapy potentially.”
Pluvicto Reduces Risk of Radiographic Progression-Free Survival by PSMAfore Trial
The randomized, open-label PSMAfore research included 469 PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) patients who had progressed after androgen receptor treatment. Registration was limited to people who had not received taxane-based chemotherapy.
This trial’s primary outcome was radiographic progression-free survival (rPFS), and Pluvicto reduced the risk by 59% compared to switching to another androgen receptor pathway inhibitor. The median rPFS for Pluvicto patients was 12 months, more than double the ARPI comparators’ 5.6 months.
At the interim analysis, overall survival (OS) was “confounded” because 84% of ARPI patients who quit due to radiographic progression switched to Pluvicto. PSMAfore keeps collecting OS information.
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Beyond survival, Pluvicto improved quality of life, delayed pain worsening, and increased prostate-specific antigen reduction.
PSMAfore found Pluvicto safer than ARPIs as an earlier treatment in this patient population. Compared to 43.1% of ARPIs, 33.9% of Pluvicto patients had grade 3–4 adverse events. Control arm side effects were also more severe.
However, Pluvicto had 5.7% discontinuation toxicity compared to 5.2% for ARPI. Pluvicto is the first FDA-approved targeted radioligand therapy, authorized in March 2022. The intravenous therapy combines ligand targeting with lutetium-177 therapy.
Pluvicto: A Targeted Radioligand Therapy for PSMA-Positive mCRPC Patients
Pluvicto delivers the radioisotope payload to PSMA-positive prostate cancer cells in the bloodstream, killing them.
PSMA-positive mCRPC patients who received ARPI and taxane-based chemotherapy can use Pluvicto. The PSMAfore trial aims to eliminate that final prerequisite and allow radioligand therapy sooner in a patient’s treatment journey, perhaps reducing chemotherapy adverse effects.
Novartis announced in December 2022 that it would negotiate a regulatory approach for earlier-line Pluvicto treatment with the FDA, but Monday’s data drop did not address it. In its third-quarter 2023 financial results on Tuesday, Novartis said it is collecting OS data and expects regulatory submissions in 2024.