Meta-Analysis: Pluvicto Extends PFS in Advanced Prostate Cancer Without Adding Toxicity

An examination of data from more than 2500 patients with advanced prostate cancer showed that patients treated with the radioligand therapy Lu-177 PSMA-617, known as Pluvicto (Novartis), offered significantly improved progression-free survival (PFS) compared with standard treatment. The results were presented Tuesday at the inaugural Multidisciplinary Radiopharmaceutical Therapy Symposium, presented by the American Society for Radiation Oncology (ASTRO) in Palm Desert, California.¹

In addition, patients receiving the radioligand treatment did not experience more adverse events (AEs) than those treated with standard-of-care therapy, including hormone-based drugs, according to a statement emailed from ASTRO. The study’s presenting author, Mohammad Arfat Ganiyani, MBBS, postdoctoral research fellow at the Miami Cancer Institute, part of Baptist Health South Florida, said the findings support research into expanding its use.

“PSMA-targeted radioligand therapy works differently than traditional androgen-signaling therapies by delivering radiation directly to prostate cancer cells,” Ganiyani said in the statement. “Together, these data support continued evaluation of radiopharmaceutical therapy earlier in the disease course and in combination with other systemic therapies.”

In cancer care, radioligand therapy combines a radioisotope with a ligand, which binds the agent to markers on specific cancer cells. This therapeutic approach has gained notice as the need grows for treatments in refractory tumor types that do not respond to existing treatments. In the case of Pluvicto, the radioactive isotope Lutetium-177 (Lu 177) is deployed to target radiation directly to cancer cells; it is delivered by intravenous infusion every 6 weeks.

Prostate cancer has been one of the major areas of research for radioligand therapies. Last year, Novartis officials estimated that the March 28, 2025, FDA approval for Pluvicto in metastatic castration-resistant prostate cancer (mCRPC) would triple the number of patients eligible for the therapy.²

Lu-177 PSMA-617 delivers targeted β-radiation to prostate cancer cells, offering a distinct mechanism beyond androgen-signaling inhibition.³ The 2025 indication allowed treatment for prostate-specific membrane antigen (PSMA)–positive disease following androgen receptor pathway inhibitor (ARPI) therapy in patients for whom it is “considered appropriate to delay chemotherapy,” Novartis officials said at the time.² The 2025 indication followed a March 2022 approval for patients with PSMA-positive mCRPC treated with ARPI therapy and taxane-based chemotherapy.⁴

The pooled analysis presented Tuesday evaluated data from 2526 patients who took part in 7 randomized trials; 1365 were enrolled in Lu-177 PSMA-617 arms and 1161 were enrolled in standard-of-care arms. Findings showed improved PFS compared with control, for a pooled HR of 0.64 (95% CI, 0.50-0.81; P < .001).¹

The analysis found no significant difference in overall survival (OS) between the 2 arms (HR, 0.91; 95% CI, 0.66-1.25; P = .55). Patients receiving radioligand therapy did not experience a significant increase in serious AEs. The pooled risk ratio for AEs of grade 3 or higher was 0.98 (95% CI, 0.83-1.14; P = .75).¹

“Across randomized trials, the consistency of progression-free survival benefit with favorable tolerability was striking, and the absence of a clear overall survival signal likely reflects post-progression treatment patterns rather than a lack of efficacy,” Ganiyani said in the statement.

References

1. Sheraz A, Syed DH, Ayudaiappan AP, et al. Safety and efficacy of Lu-177 PSMA-617 versus established therapies in mCRPC: pooled evidence from randomized phase II/III trials. Presented at: Multidisciplinary Radiopharmaceutical Therapy Symposium, American Society for Radiation Oncology (ASTRO); February 17-18, 2026; Palm Desert, CA. Abstract 1.
2. FDA approves radioligand therapy Pluvicto for earlier use before chemotherapy in PSMA-positive metastatic castration-resistant prostate cancer. News release. Novartis. March 28, 2025. Accessed March 28, 2025. https://bit.ly/3E0xRG3
3. Konopnicki A, Zaliznyak M, Roy M, Jana B. The therapeutic use of 177 Lu-PSMA-617 radioligand therapy in prostate cancer treatment: a review of literature and ongoing trials. Discov Oncol. 2024;15(1):791. doi:10.1007/s12672-024-01680-z.
4. Fallah J, Agrawal S, Gittleman H, et al. FDA approval summary: lutetium Lu 177 vipivotide tetraxetan for patients with metastatic castration-resistant prostate cancer. Clin Cancer Res. 2023;29(9):1651-1657. doi:10.1158/1078-0432.CCR-22-2875