Abstract
Background
Sipuleucel-T has demonstrated survival benefit in phase 3 trials but is utilized in few men with metastatic castration-resistant prostate cancer (mCRPC) in part due to low rates of PSA and objective response. Given the requirement to develop immune-mediated antitumor activity as vaccine-based therapy, sipuleucel-T may have delayed clinical activity. We explored this in a cohort of men from PROCEED (NCT01306890), an FDA-requested outcomes registry, and in a separate institutional cohort of mCRPC patients treated with sipuleucel-T at Dana-Farber Cancer Institute (DFCI).
Methods
Men with mCRPC who received 3 infusions of sipuleucel-T and did not initiate a new mCRPC directed therapy for ≥6 months after completion of sipuleucel-T were included. All patients had rising PSA before starting sipuleucel-T and available post-treatment PSA measurements. Clinical outcomes of interest included: PSA50 response rate, time to subsequent mCRPC directed therapy, and overall survival (OS).
Results
Of 1902 men with mCRPC treated in PROCEED and 255 patients treated consecutively with sipuleucel-T between 4/2010 and 4/2017 at DFCI, 171 and 28 patients were included, respectively. In the PROCEED sample, PSA50 response was observed in 34 (19.9%) of patients at a median of 5.5 months (IQR: 3.9–9.5) since the last sipuleucel-T infusion; median time to subsequent mCRPC directed therapy was 10 months (95% CI: 9–11); and median OS was 49 months (95% CI: 43–NR). In the DFCI cohort, PSA50 response was observed in 4 (14.3%) of patients at a median of 6.3 months (IQR: 4.7–7.0); median time to subsequent mCRPC directed therapy was 9 months (95% CI: 9–11); and median OS was 60 months (95% CI: 51–74).
Conclusions
In this analysis of mCRPC patients treated with sipuleucel-T who did not immediately initiate subsequent therapy using two datasets, delayed PSA response was observed in a subset of patients indicating delayed clinical activity.
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Acknowledgements
The authors would like to acknowledge the patients and study personnel who contributed to this research.
Funding
PROCEED (NCT01306890) was funded by Dendreon Pharmaceuticals LLC.
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The authors confirm contribution to the paper as follows: study conception and design: ADC, LK, MH, SCF, XXW. Data collection: MH, XXW. Analysis and interpretation of results: ADC, LK, MH, SCF, XXW. Draft manuscript preparation: ADC, LK, XXW. All authors reviewed the results and approved the final version of the manuscript.
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There are no disclosures for work conducted at Dana-Farber Cancer Institute. AH: Consulting or Advisory Role: Merck Sharp & Dohme ADC: Advisory Role: Clovis, Dendreon, Bayer and Eli Lilly. CS: Consulting or Advisory Role: Sanofi, Janssen, Astellas Pharma, Bayer, Genentech, Pfizer, Lilly, Research Funding: Janssen Biotech (Inst), Astellas Pharma (Inst), Sanofi (Inst), Bayer (Inst), Sotio (Inst), Dendreon (Inst); Patents, Royalties, Other Intellectual Property: Pathenolide (Indiana University): dimethylaminoparthenolide (Leuchemix); Exelixis: Abiraterone plus cabozantinib combination. Stock or Other Ownership: Leuchemix. MH: Currently employee of Dendreon. SCF: Former employee of Dendreon. XW: Advisory Role: Novartis; Research funding: Bristol Myers Squibb (Inst).
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Wei, X.X., Kwak, L., Hamid, A. et al. Outcomes in men with metastatic castration-resistant prostate cancer who received sipuleucel-T and no immediate subsequent therapy: experience at Dana Farber and in the PROCEED Registry. Prostate Cancer Prostatic Dis 25, 314–319 (2022). https://doi.org/10.1038/s41391-022-00493-x
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DOI: https://doi.org/10.1038/s41391-022-00493-x