SIPULEUCEL-T FOR PROSTATE CANCER

he first and only immunotherapy product for advanced cancer, sipuleucel-T (Provenge), has not been widely used clinically since its launch 10 years ago, and has been largely eclipsed by two drugs launched since then — the androgen-receptor signaling pathway inhibitors (ASPIs) abiraterone acetate (Zytiga) and enzalutamide (Xtandi).

But new data from a retrospective observational study involving more than 6000 participants show that men with advanced prostate cancer who received sipuleucel-T had a significantly prolonged overall survival.

The median overall survival was 34.9 months with sipuleucel-T vs 21.0 months in men who were treated with ASPIs in the first-line setting.

The study was published October 7 in Advances in Therapy.

"These data highlight that Provenge is a viable option for patients with metastatic castration-resistant prostate cancer and should be considered and used as a treatment for a subset of patients eligible to receive this medication," said lead author Rana McKay, MD, an associate professor of medicine at the University of California-San Diego School of Medicine.

However, an expert approached for comment cautioned that these new data should be viewed as hypothesis-generating only.

Daniel Geynisman, MD, assistant professor, Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, pointed out that sipuleucel-T is the only immunotherapy FDA- approved specifically for castration-resistant prostate cancer.

Often referred to as a vaccine, the product is an autologous active cellular immunotherapy, made from the patient's own white blood cells, which are collected and then reprogrammed to attack cancer cells.

"It is infrequently used in clinical practice compared to androgen pathway inhibitors such as abiraterone acetate or enzalutamide, due to perceived marginal survival benefit, lack of a PSA response, and inability to gauge a patient's response, and also cost," Geynisman commented.

Although this new analysis suggests a survival benefit with use of sipuleucel-T, it should be considered "as hypothesis-generating only, given its severe limitations in controlling for key clinical variables — such as PSA, Gleason score, performance status and other key laboratory values — that may severely differentiate the group of men who did vs did not receive sipuleucel-T," said Geynisman.

"Sipuleucel-T remains an option for men, but guidelines and clinical practice cannot be altered based on this analysis alone," he added.

He emphasized that these results do not suggest that sipuleucel-T is superior to abiraterone acetate or enzalutamide in improving overall survival. "They suggest that men who at some point in their treatment trajectory received sipuleucel-T have superior overall survival," he explained. "These results are once again intriguing and supportive of the use of sipuleucel-T, but as any claims-based research remain only hypothesis-generating given the multiple possible confounders."

Study Details

For their study, McKay and colleagues developed multivariable models to analyze data obtained from the longitudinal Medicare Fee-for-Service 100% administrative claims research dataset with patient-level linkage to the National Death Index.

The authors hypothesized that patients receiving sipuleucel-T would have improved survival compared with users of other treatments, potentially because of its distinct mechanism of action compared with other mCRPC-directed therapies.

The model included 6044 men with mCRPC who were treatment naive and had continuous Medicare eligibility (Parts A, B, and D) over a 3-year observation starting in 2014.

Analyses were conducted in two cohorts. The first included men who received first-line sipuleucel-T vs those who received first-line ASPIs, and these patients were permitted to receive any other type of therapy in subsequent lines. The second analysis was the "any-line cohort" of patients who were treated with sipuleucel-T vs those treated with any-line ASPIs, but who did not receive sipuleucel-T.

During the 36-month observation period, 75% of patients receiving ASPIs in any line without sipuleucel-T had one or two lines of therapy, while 75% of those treated with sipuleucel-T at any time received two to three lines of therapy. Among men who received sipuleucel-T, 71% received it as first-line therapy.

In the overall analysis, median survival was 22.9 months. For the first line cohort, patients who received sipuleucel-T as a first-line treatment had 44% reduction in the risk of death at 36 months vs those receiving ASPIs (adjusted hazard ratio [HR], 0.56; P < .0001).

A similar pattern was observed in the any-line cohort. Those in the sipuleucel-T group had a 41% decrease in the risk of death at 36 months vs patients receiving an oral ASPI (without sipuleucel-T) (adjusted HR, 0.59; P < .0001). This extrapolated to a 14.5-month difference in median overall survival between the any-line groups, with duration of survival 35.2 months (sipuleucel-T) vs. 20.7 months (ASPI, without sipuleucel-T).

In an exploratory analysis, no survival differences were seen when the sequence of first-line sipuleucel-T followed by ASPIs was compared with first-line ASPIs followed by sipuleucel-T (HR, 1.17; P = .521). The authors did note that survival outcomes were significantly improved when sipuleucel-T was used with an ASPI when compared with either an ASPI used alone or if two ASPIs were used in sequence (HR, 0.48; P < .0001).

"Even given the potential limitations associated with claims analyses, such as selection bias and confounding by indication, this research provides important insights into real-world treatment outcomes and is complementary with other recently published real-world evidence analyses from other data sources," the authors conclude.

The study was funded by Dendreon Pharmaceuticals, LLC. McKay reports research funding from Pfizer, Bayer, and Tempus, as well as advisory board/consulting roles for Bayer, Bristol-Myers Squibb, Dendreon, Exelixis, Johnson and Johnson, Novartis, Pfizer Sanofi, and Vividion. Several coauthors also report relationships with industry. The full list can be found with the original article.

Adv Ther. Published online October 7, 2020. Full text