At the European Society of Medical Oncology (ESMO) Congress 2025, held in Berlin, Germany from 17 to 21 October, results from the global, multicentre, open-label, randomised Phase III prostate-specific membrane antigen (PSMAddition) clinical trial (NCT04720157) were presented. This trial evaluated the safety and efficacy of the combination of Novartis’s Pluvicto (lutetium Lu 177 vipivotide tetraxetan), an intravenous radioligand therapy (RLT) that combines a ligand with a therapeutic radionuclide lutetium-177 and standard of care (SOC) androgen receptor pathway inhibitor + androgen deprivation therapy (ARPI + ADT) as first-line treatment for patients with PSMA-positive metastatic hormone-sensitive prostate cancer (mHSPC).
According to GlobalData’s patient-based Prostate Cancer: Eight-Market Drug Forecast and Market Analysis, the number of diagnosed prevalent drug-treated mHSPC cases in the eight major markets (8MM: China, France, Germany, Italy, Japan, Spain, the UK and the US) will rise from 196,867 in 2025 to 244,101 cases by 2033.
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In the PSMAddition clinical trial, a total of 1,144 patients with treatment naïve or minimally treated PSMA-positive mHSPC were randomised 1:1 to experimental arm A (Pluvicto + ARPI + ADT; n=572) and comparator arm B (ARPI + ADT; n=572). The primary endpoint, radiographic progression-free survival (rPFS), assessed by a blinded independent review committee, was statistically significant and clinically meaningful in this study. The risk of rPFS or death was reduced by 28% in arm A (HR 0.72; 95% CI: 0.58, 0.90; p=0.002) compared to arm B, and the result was consistent across different subgroups.
The key secondary endpoint, overall survival (OS), showed a positive trend in arm A (HR 0.84; 95% CI: 0.63, 1.13; p=0.125), although data were immature at the time of analysis and follow-up is ongoing. The results showed that arm A showed higher complete response rates (57.1% vs. 42.3%) and overall response rate (85.3% vs. 80.8%) than arm B, and delayed progression to mCRPC (HR 0.70; 95% CI: 0.58, 0.84). Pluvicto demonstrated a safety and tolerability profile consistent with previous findings from the PSMAfore and VISION studies. Grade ≥3 adverse events were observed in 50.7% of patients treated with Pluvicto plus SOC, versus 43% with SOC alone, with dry mouth, fatigue, nausea, hot flushes and anaemia reported as the most frequent all-grade events.
Pluvicto was first approved by the US Food and Drug Administration (FDA) in 2022 for PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) following ARPI and taxane-based therapy, based on the VISION trial. In 2025, the FDA expanded its approval to include patients with PSMA-positive mCRPC before chemotherapy. ADT and ARPI were previously the only approved treatments for mHSPC, with no RLT available in this earlier setting. The positive PSMAddition results, therefore, represent a major milestone, and Novartis plans to submit these new data for regulatory approval by the end of 2025. Despite the strong rPFS benefit, important clinical questions remain regarding optimal patient selection, treatment duration and long-term toxicities, which will define Pluvicto’s role in mHSPC management.
According to GlobalData’s analyst consensus forecast, global sales for Pluvicto are projected to reach $4.3 billion by 2033, and the new indication could significantly expand its commercial potential. Novartis has scaled up its US manufacturing capacity and is establishing RLT production facilities in Japan and China to meet anticipated global demand. No active Phase III competitors are currently targeting the PSMA-positive mHSPC segment, positioning Pluvicto as the first-mover in this space. Novartis is also exploring earlier disease settings, including the Phase III PSMA-DC trial evaluating Pluvicto in oligometastatic prostate cancer.
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By GlobalDataMeanwhile, the RLT space continues to attract major investments, with Eli Lilly acquiring POINT Biopharma for $1.4 billion, AstraZeneca purchasing Fusion Pharmaceuticals for $2.4 billion, Bristol Myers Squibb acquiring RayzeBio for $4.1 billion and Novartis buying Mariana Oncology for $1.7 billion. If the final analysis shows an OS benefit and the drug gains approval in this setting, Novartis will be well-positioned to capitalise on Pluvicto.
