Pluvicto Approval Launches Theranostics in Prostate Cancer

Targeted Therapies in Oncology, July 2, 2022, Volume 11, Issue 10
Pages: 77

Ashok Muthukrishnan, MD, MS, addresses the recent FDA approval of lutetium 177Lu vipivotide tetraxetan and looks to the potential of radioimmunotheranostics on the horizon.

In an update to his original article, “PSMA Theranostics Is Poised to Change Prostate Cancer Landscape,”1 Ashok Muthukrishnan, MD, MS, addresses the recent FDA approval of lutetium (177Lu) vipivotide tetraxetan (Pluvicto)2 and looks to the potential of radioimmunotheranostics on the horizon.

Prostate cancer theranostics is at an exciting crossroads, with recent FDA approvals of prostate-specific membrane antigen (PSMA)-based cancer molecular imaging and therapy agents.3 The commercially available 18F-DCFPyL (Pylarify), and the pair of 68Ga-PSMA-11 imaging tracer drugs (Illuccix and Locametz) provide 3 options. Although there was some initial confusion on the specific indications for these agents, National Comprehensive Cancer Network and Society of Nuclear Medicine and Molecular Imaging guidelines had recommended the use of all these PET imaging agents interchangeably for initial staging of high-risk prostate cancer, biochemical recurrence, and for patient selection before PSMA-directed therapy.

Recent enthusiasm within the oncology community and patients with prostate cancer stems from lutetium (177Lu) vipivotide tetraxetan (Pluvicto), which received FDA approval in March 2022. The decision to approve 177Lu vipivotide tetraxetan was supported by findings from the international, randomized, phase 3 VISION study (NCT03511664).

In VISION, treatment with 177Lu vipivotide tetraxetan combined with standard of care (SOC) therapy demonstrated significant improvement in overall survival as well as radiographic progression-free survival compared with SOC alone in patients with PSMA-positive metastatic castration-resistant prostate cancer.

The fanfare and excitement came to a temporary halt with the announcement from Novartis, the manufacturer, about a voluntary temporary suspension of drug production because of potential quality issues in their manufacturing process.4 This issue has recently been resolved by the manufacturer and the drug should be available at the time of this publication.

Just like Lutathera, Pluvicto uses 177Lu that emits beta radiation, effectively delivering “precision” radiation targeted at the PSMA receptors, which is highly expressed in prostate cancer cell lines compared with other normal cells.5

Additionally, its degree of expression has been identified as an independent marker for risk stratification in predicting disease recurrence following curative therapy.5

Trials evaluating PSMA-targeted 177Lu radioligand therapy have shown that the drug is highly effective when added to SOC,6 with a meta-analysis showing that around 75% of patients had a reduction of PSA levels, and a further 46% had PSA levels drop by more than half.7

Within the next few years, it would not be surprising to see α-based PSMA agents dominate if not entirely replace 177Lu-based agents and play an integral role in prostate cancer therapy practice. Taking it a notch higher, radioimmunotheranostics might usher in the next line of therapy tools for prostate cancer and beyond. One such great example is the antibody-to-prostate stem cell antigen that could be the next potential agent for prostate cancer diagnosis and therapy.8

REFERENCES:

1. Muthukrishnan A. PSMA theranostics is poised to change prostate cancer landscape. Target Ther Oncol.May 22, 2021.Accessed June 27, 2022. targetedonc.com/link/1830

2. FDA approves Pluvicto for metastatic castration-resistant prostate cancer. FDA. March 23, 2022. Accessed June 27, 2022. https://bit.ly/3Og8hwx

3. Grauer LS, Lawler KD, Marignac JL, Kumar A, Goel AS, Wolfert RL. Identification, purification, and subcellular localization of prostate-specific membrane antigen PSM’protein in the LNCaP prostatic carcinoma cell line. Cancer Res. 1998;58(21):4787-4789.

4. Novartis provides update on production of radioligand therapy medicines. News release. Novartis. May 5, 2022. Accessed June 24, 2022. https://bit.ly/3tZV6rP

5. Hupe MC, Philippi C, Roth D, et al. Expression of prostate-specific membrane antigen (PSMA) on biopsies is an independent risk stratifier of prostate cancer patients at time of initial diagnosis. Front Oncol. 2018;8:623. doi:10.3389/fonc.2018.00623

6. Sartor O, de Bono J, Chi KN, et al; VISION Investigators. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021;385(12):1091-1103. doi:10.1056/NEJMoa2107322

7. Yadav MP, Ballal S, Sahoo RK, Dwivedi SN, Bal C. Radioligand therapy with 177Lu-PSMA for metastatic castration-resistant prostate cancer: a systematic review and meta-analysis. AJR Am J Roentgenol. 2019;213(2):275-285. doi:10.2214/AJR.18.20845

8. Arndt C, Bergmann R, Striese F, et al. Development and functional characterization of a versatile radio-/immunotheranostic tool for prostate cancer management. Cancers (Basel). 2022;14(8):1996. doi:10.3390/cancers14081996