Dataset Information

Factors Associated With Use of Sipuleucel-T to Treat Patients With Advanced Prostate Cancer.

ABSTRACT:

Importance

Sipuleucel-T is an immunotherapy that has been approved for use in patients with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). However, sipuleucel-T may not be available to some patients because of logistics, cost, and practice structure.

Objective

To identify factors associated with the adoption of sipuleucel-T across the United States.

Design, setting, and participants

In this retrospective cohort study, patients with prostate cancer who received therapy for mCRPC (docetaxel, abiraterone acetate, enzalutamide, cabazitaxel, radium 223, or sipuleucel-T) from January 1, 2010, through June 30, 2016, were identified in a large claims database of commercially insured patients. Patients who received sipuleucel-T were compared with patients who received any of the other treatments for mCRPC but did not receive sipuleucel-T. Data were analyzed from May 3, 2018, to February 24, 2019.

Exposures

Sipuleucel-T treatment.

Main outcomes and measures

Patterns of treatment that involved the use of sipuleucel-T were elucidated, and binomial logistic regression was conducted to determine patient and physician factors that were associated with the use of sipuleucel-T and whether patients received sipuleucel-T in isolation or concurrently with other therapies.

Results

Among 7272 patients who received a treatment for mCRPC, 730 (10.0%) received sipuleucel-T. Mean (SD) age of patients in the entire cohort was 73.2 (9.2) years; 6739 (92.7%) were non-Hispanic and 975 (13.4%) were black. In multivariable analysis, patients who were Hispanic (odds ratio [OR], 0.57; 95% CI, 0.38-0.86) or lived in the Pacific region (OR, 0.66; 95% CI, 0.45-0.97) had lower odds of receiving sipuleucel-T than patients who were not Hispanic or who lived in the South Atlantic region. Patients with higher incomes had greater odds of receiving sipuleucel-T than patients with incomes of less than $50?000 (OR, 1.29 [95% CI, 1.04-1.61] for $50?000-$99?000; OR, 1.43 [95% CI, 1.10-1.85] for >$99?000). Patients treated by a urologist had greater odds of receiving sipuleucel-T than patients not treated by a urologist (OR, 8.89; 95% CI, 7.10-11.11). Sixty-seven patients received concurrent therapies with sipuleucel-T, most commonly abiraterone or enzalutamide, but no factors were independently associated with patients receiving sipuleucel-T concurrent with other therapies for mCRPC.

Conclusions and relevance

In this study, 1 of 10 patients with prostate cancer who were treated for mCRPC received sipuleucel-T, with several variables associated with its use. Identifying disparities in receipt of sipuleucel-T may affect future access to this and other highly specialized cancer therapies by defining barriers to treatment that could be addressed in future studies.

SUBMITTER: Caram MEV

PROVIDER: S-EPMC6481456 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Factors Associated With Use of Sipuleucel-T to Treat Patients With Advanced Prostate Cancer.

Caram Megan E V MEV Ross Ryan R Lin Paul P Mukherjee Bhramar B

JAMA network open 20190405 4

<h4>Importance</h4>Sipuleucel-T is an immunotherapy that has been approved for use in patients with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). However, sipuleucel-T may not be available to some patients because of logistics, cost, and practice structure.<h4>Objective</h4>To identify factors associated with the adoption of sipuleucel-T across the United States.<h4>Design, setting, and participants</h4>In this retrospective cohort study, patients ...[more]

PMID: 31002323

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Project description:Historically, chemotherapy has remained the most commonly utilized therapy in patients with metastatic cancers. In prostate cancer, chemotherapy has been reserved for patients whose metastatic disease becomes resistant to first line castration or androgen deprivation. While chemotherapy palliates, decreases serum prostate specific antigen and improves survival, it is associated with significant side effects and is only suitable for approximately 60% of patients with castrate-resistant prostate cancer. On that basis, exploration of other therapeutic options such as active secondary hormone therapy, bone targeted treatments and immunotherapy are important. Until recently, immunotherapy has had no role in the treatment of solid malignancies aside from renal cancer and melanoma. The FDA-approved autologous cellular immunotherapy sipuleucel-T has demonstrated efficacy in improving overall survival in patients with metastatic castrate-resistant prostate cancer in randomized clinical trials. The proposed mechanism of action is reliant on activating the patients' own antigen presenting cells (APCs) to prostatic acid phosphatase (PAP) fused with granulocyte-macrophage colony stimulating factor (GM-CSF) and subsequent triggered T-cell response to PAP on the surface of prostate cancer cells in the patients body. Despite significant prolongation of survival in Phase III trials, the challenge to health care providers remains the dissociation between objective changes in serum PSA or on imaging studies after sipleucel-T and survival benefit. On that basis there is an unmet need for markers of outcome and a quest to identify immunologic or clinical surrogates to fill this role. This review focuses on the impact of sipuleucel-T on the immune system, the T and B cells, and their responses to relevant antigens and prostate cancer. Other therapeutic modalities such as chemotherapy, corticosteroids and GM-CSF and host factors can also affect immune response. The optimal timing for immunotherapy, patient selection and best sequencing with other prostate cancer therapies remain to be determined. A better understanding of immune response may help address these issues.

Project description:Opinion statementAt present, sipuleucel-T represents the only approved immunotherapy for prostate cancer. Sipuleucel-T is an autologous cellular therapy, which primes autologous antigen-presenting cells against the prostatic acid phosphatase (PAP) antigen. For patients with metastatic castrate-resistant prostate cancer (CRPC) who are asymptomatic or minimally symptomatic, sipuleucel-T monotherapy is one of the standard of care treatment options pre- or postdocetaxel. With the approval of new treatments, including abiraterone and enzatutamide, sequencing and combination of these treatments with sipuleucel-T represent unanswered questions facing the field. Whereas steroids that are coadministered with abiraterone and chemotherapy have long been thought to be immunosuppressive, early results show that concurrent abiraterone and prednisone does not significantly impact the ability to develop immune responses to this treatment. Additional clinical data are needed to elucidate optimal sequencing of therapeutic agents in CRPC. Several novel immunotherapies are currently in development, and enrollment in clinical trials should be considered. These include PROSTVAC-VF, a viral vaccine that encodes PSA and T-cell costimulatory molecules, which is currently undergoing phase III clinical trials. DNA plasmid-based vaccines targeting different antigens, including PAP, also are under investigation. Immune checkpoint blockade with ipilimumab, a monoclonal antibody against CTLA-4, which is approved for metastatic melanoma, also is being evaluated. Whereas this treatment failed to show significant improvement in overall survival in CRPC patients treated with docetaxel, results from a phase III trial in the predocetaxel setting are pending. Conventional therapies for prostate cancer, such as radiation and hormonal therapy, may have immunomodulatory effects. Future areas for research include the sequencing and combination of immunotherapies as well as other conventional therapies.

Project description:IntroductionSince sipuleucel-T approval in 2010, the treatment landscape for metastatic castration-resistant prostate cancer (mCRPC) now includes the androgen-receptor signaling pathway inhibitors (ASPIs) abiraterone acetate or enzalutamide. In 2013 and 2014, these oral agents were approved for use in men with metastatic prostate cancer who had minimal to no symptoms. We compared overall survival (OS) in men who received their first mCRPC treatment using the Medicare Fee-for-Service 100% administrative claims research dataset with patient-level linkage to the National Death Index.MethodsThis retrospective cohort analysis (January 2013 to December 2017) included men who were chemo-naïve at treatment start in 2014 and who had continuous Medicare Parts A, B, and D eligibility during the 3-year observation period. We compared: first-line sipuleucel-T vs. first-line ASPIs and any-line sipuleucel-T vs. any-line ASPIs (without sipuleucel-T). We used a multivariable regression model to help control for potentially confounding factors while assessing survival outcomes.ResultsThe model included 6044 eligible men (average age 75-78 years) with similar disease severity; > 80% were white. Median OS, presented as sipuleucel-T vs. ASPI, was 35.2 vs. 20.7 months (n, 906 vs. 5092; any-line cohort) and 34.9 vs. 21.0 months (n, 647 vs. 4810; first-line cohort). Model outcomes indicated sipuleucel-T was associated with significantly prolonged OS compared with ASPIs: adjusted hazard ratio, 0.59 (95% CI 0.527-0.651) and 0.56 (0.494-0.627) for the any-line and first-line cohorts, respectively.ConclusionThis analysis suggests use of sipuleucel-T at any time was associated with improved OS compared with ASPI use alone. Of note, these analyses are intended as descriptive rather than definitive as this dataset contains limited data on key clinical factors. While selection bias is a risk in secondary claims data, this research provides important insight into real-world treatment outcomes.

Project description:BackgroundSipuleucel-T is a US Food and Drug Administration-approved autologous cellular immunotherapy that improves survival in patients with metastatic castration-resistant prostate cancer (mCRPC). We examined whether administering ipilimumab after sipuleucel-T could modify immune and/or clinical responses to this treatment.MethodsA total of 50 patients with mCRPC were enrolled into a clinical trial (NCT01804465, ClinicalTrials.gov) where they received ipilimumab either immediately or delayed 3 weeks following completion of sipuleucel-T treatment. Blood was collected at various timepoints of the study. Luminex assay for anti-prostatic acid phosphatase (PAP) and anti-PA2024-specific serum immunoglobulin G (IgG) and ELISpot for interferon-γ (IFN-γ) production against PAP and PA2024 were used to assess antigen-specific B and T cell responses, respectively. Clinical response was defined as >30% reduction in serum prostate-specific antigen levels compared with pretreatment levels. The frequency and state of circulating immune cells were determined by mass cytometry by time-of-flight and statistical scaffold analysis.ResultsWe found the combination to be well tolerated with no unexpected adverse events occurring. The timing of ipilimumab did not significantly alter the rates of antigen-specific B and T cell responses, the primary endpoint of the clinical trial. Clinical responses were observed in 6 of 50 patients, with 3 having responses lasting longer than 3 months. The timing of ipilimumab did not significantly associate with clinical response or toxicity. The combination treatment did induce CD4 and CD8 T cell activation that was most pronounced with the immediate schedule. Lower frequencies of CTLA-4 positive circulating T cells, even prior to treatment, were associated with better clinical outcomes. Interestingly, these differences in CTLA-4 expression were associated with prior localized radiation therapy (RT) to the prostate or prostatic fossa. Prior radiation treatment was also associated with improved radiographic progression-free survival.ConclusionCombining CTLA-4 blockade with sipuleucel-T resulted in modest clinical activity. The timing of CTLA-4 blockade following sipuleucel-T did not alter antigen-specific responses. Clinical responses were associated with both lower baseline frequencies of CTLA-4 expressing T cells and a history of RT. Prior cancer therapy may therefore result in long-lasting immune changes that influence responsiveness to immunotherapy with sipuleucel-T and anti-CTLA-4.

Dataset Information

Factors Associated With Use of Sipuleucel-T to Treat Patients With Advanced Prostate Cancer.

Importance

Objective

Design, setting, and participants

Exposures

Main outcomes and measures

Results

Conclusions and relevance

Publications

Factors Associated With Use of Sipuleucel-T to Treat Patients With Advanced Prostate Cancer.

Similar Datasets

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