ESMO 2023: Novartis' Pluvicto Shows Promising Results in Prostate Ca. Trials

Novartis’ radiotherapy drug, Pluvicto, has demonstrated significant benefits in treating prostate cancer, showing a 57% reduction in the risk of prostate cancer progression. While Pluvicto has displayed potential benefits, the mixed results regarding patient survival have raised regulatory questions.

In the Phase III PSMAfore trial presented at the 2023 European Society for Medical Oncology (ESMO) Congress, Pluvicto (Lutesyum Lu 177 vipivotide tetraxetan), achieved a significant 57% reduction in the risk of disease progression or death in patients with PSMA-positive, metastatic castration-resistant prostate cancer (mCRPC) who hadn't undergone prior taxane-based chemotherapy. The remarkable improvement in radiographic progression-free survival (rPFS) is indeed a significant breakthrough in the field of oncology, with Pluvicto™ more than doubling the median rPFS to 12.0 months, as per the updated analysis.

“The rPFS data are impressive and the treatment effect is comparable with what was observed in the VISION trial. We look forward to a future where Pluvicto may be a viable therapy for patients in need of alternative, earlier options.” said Dr. Oliver Sartor, PSMAfore Co-Principal Investigator, Chairman of the Trial Steering Committee.

However, this victory was shadowed by concerns related to overall patient survival. The drug's use was linked to a 16% increased risk of death. But this data is complex, given that 84% of patients in the control group, whose disease had progressed, later received Pluvicto. 

After adjusting for this crossover, Pluvicto™ showed a 20% reduction in death risk compared to the control group. Despite this, the FDA remains cautious. A negative trend in overall survival is a significant red flag, and while it doesn't conclusively indicate harm from Pluvicto™, it does raise questions.

“These promising results from PSMAfore could change the treatment paradigm for advanced prostate cancer by allowing patients to potentially avoid or delay taxane-based chemotherapy, which carries a heavy burden of side effects. While data collection for overall survival continues, the consistency of the benefit observed on other clinically meaningful efficacy endpoints, together with improved quality of life and favorable safety profile, show the potential of Pluvicto for taxane-naïve patients with mCRPC,” said Jeff Legos, Executive Vice President, Global Head of Oncology Development at Novartis.

Adverse events were also carefully observed, with grade 3 or higher events seen in 34% of patients on Pluvicto™, compared to 44% in the control group. The most prevalent side effect in the Pluvicto™ group was dry mouth, experienced by over half of the patients, but only 1% of these cases were grade 3 or higher. Both arms of the trial had similar rates of high-grade anemia, around 6%, and side effects led to discontinuation in roughly 5.7% and 5.2% of patients in the Pluvicto™ and control arms, respectively.

The trial continues to evaluate overall survival data, with the next interim analysis set for 2024. Despite the concerns, Novartis remains hopeful, estimating that Pluvicto™ could achieve over $2 billion in peak sales.