Novartis has shared detailed data showing its radioligand therapy Pluvicto could slow the progression of certain hormone-sensitive prostate cancers ahead of a planned application with the FDA.
Pluvicto plus standard of care significantly reduced the risk of radiographic progression or death by 28% versus standard of care alone in patients with PSMA-positive metastatic hormone-sensitive prostate cancer (mHSPC), according to Novartis. The standard of care includes androgen deprivation therapy (ADT) and an androgen receptor pathway inhibitor (ARPI) such as Pfizer and Astellas’ Xtandi.
Details from the phase 3 PSMAddition trial were presented Sunday at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin.
While Novartis said the improvement is statistically significant and clinically meaningful, its magnitude isn’t the most impressive historically seen with Pluvicto or in mHSPC albeit in different treatment settings and different comparators.
The FDA in March approved Pluvicto for PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have had an ARPI but not chemotherapy based on results from the phase 3 PSMAfore trial showing the radiopharmaceutical lowered the risk of radiographic progression or death by 59% compared to a change in ARPI.
Xtandi got its mHSPC label from the FDA in 2019 after the phase 3 Arches trial linked Xtandi plus ADT to a 61% reduction in radiographic progression or death versus ADT alone.
At ESMO 2025, AstraZeneca also detailed positive phase 3 data for its AKT inhibitor Truqap in PTEN-deficient de novo mHSPC. In the CAPItello-281 trial, Truqap, used on top of Johnson & Johnson’s ARPI Zytiga and ADT, cut the risk of radiographic progression or death by 19% compared with Zytiga, ADT and placebo, according to an abstract. Here, PTEN deficiency is defined as at least 90% of viable malignant cells with no specific cytoplasmic staining by immunohistochemistry tests.
Truqap’s efficacy increased to 25% and 32% when using more stringent PTEN deficiency criteria at 95% and 100%, respectively.
Data on whether Pluvicto can extend patients’ lives remained immature in the PSMAddition trial. Novartis is now reporting an early positive trend, linking the addition of Pluvicto to a preliminary 16% reduction in the risk of death. The trial remains ongoing for more mature overall survival (OS) data.
The Swiss pharma said it plans to submit to regulatory authorities for approvals by the end of the year, pending final radiographic progression-free survival data and an updated OS look. Previously, a negative early OS trend confounded by a high control arm crossover rate delayed the FDA’s approval for Pluvicto based on the PSMAfore data.
By Novartis’ estimate, an approval in mHSPC would double the number of patients eligible for Pluvicto. An earlier manifestation of prostate cancer, mHSPC would progress to mCRPC typically within 20 months, according to Novartis.
However, on Novartis’ second-quarter earnings call in July, a Goldman Sachs analyst suggested side effects related to continence and sexual function may limit the Pluvicto regimen’s uptake among mHSPC patients, who are generally younger than mCRPC patients.
At the time, Novartis CEO Vas Narasimhan said that doctors are generally satisfied with Pluvicto’s tolerability profile, and that the sexual function problem is rather the doing of the hormonal therapies that patients are taking.
In PSMAddition, grade 3 or above adverse events were reported in 50.7% of patients in the Pluvicto arm, versus 43% in the control group. Sunday’s presentation of PSMAddition, which included discussions about side effects that had happened in at least 10% of patients in the Pluvicto arm and “safety topics of interest,” did not show any continence or sexual function-related problems.
“In metastatic prostate cancer, choosing the most efficacious treatment early is crucial, even at initial diagnosis,” Scott Tagawa, M.D., from Weill Cornell Medicine said in an Oct. 19 statement. “These findings suggest that combining [Pluvicto] with standard of care hormonal therapy offers patients more time without disease progression, a safety profile with adverse events that are most often low grade and managed with supportive care, and an encouraging trend in overall survival.”
Based on a potential approval in mHSPC, Novartis has estimated that Pluvicto could reach peak sales above $5 billion.
Editor's note: The story has been updated with additional information on PSMAddition's safety data.