Treatment approaches for prostate cancer in sub-Saharan Africa

Introduction

Cancer incidence has been rising in sub-Saharan Africa (SSA). Given significant disparities in access to therapies for common cancers in SSA (given costs, need for infrastructure, and limited trained personnel to administer therapies), we previously reviewed particular oncologic therapies that may benefit cancer patients most in SSA (1). Our prior work identified an urgent need to address disparities in drug access given the rising incidence of cancer in SSA with often early age at diagnosis, late-stage presentation, and poor survival (1). Here, we expand on our original work with a particular focus with prostate cancer (CaP).

CaP is a significant cause of cancer-related morbidity and mortality globally. No definitive causes of CaP have been identified to date but, increasing age, a positive family history and SSA ancestry are strongly linked to its development (2). The disproportionate share of this burden of cancer-related morbidity and mortality is concentrated in low- and middle-income countries (LMIC) countries particularly the SSA (3). This disparity has been linked to socioeconomic factors and genetic susceptibility (4).

Among all the cancers in SSA, CaP has the highest age-standardized incidence, mortality and 5-year prevalence rate (5). The incidence on the African continent varies substantially, with the highest rates in the Southern (64.1 per 100,000 cases), followed by the Northern (35.9 per 100,000), and the Western region (31.9 per 100,000). The Eastern region and Western region reported rates of 23.9 per 100,000 and 13.2 per 100,000, respectively (6). The International Agency for Research in Cancer (IARC) also estimated CaP mortality rate from approximately 28,006 deaths in 2010 to approximately 57,048 deaths in 2030 which represented a 104% increase in the number of CaP deaths in Africa over the next two decades (7). To estimate both cancer incidence and mortality in SSA, information from the year 2020 was obtained from the International Agency for Research on Cancer’s GLOBOCAN database. Findings included approximately 800,000 new cancer cases and approximately 500,000 cancer deaths estimated in SSA in 2020, with CaP leading in incidence (77,300 cases), and CaP representing the most common cancer-causing death in 26 countries (8).

Although African ancestry represents a significant risk factor for CaP, there is relatively sparse data on the aggressiveness of CaP within Africa as most countries are at the early stages of optimizing oncologic care. Cancer awareness in this region is still limited, and access to specialized oncologic management is scarce. However, several studies have suggested that CaP is growing faster and there is an earlier transformation from latent to aggressive CaP among men of SSA ancestry. Data suggests that CaP was significantly more aggressive between African Americans and Southern Bantus (which includes hundreds of native African ethnic groups in areas including areas such as Democratic Republic of Congo, Kenya, Tanzania, Angola, Zambia, Malawi, Mozambique, Botswana, South Africa) with Gleason score >7 (17% and 36%, respectively), and with prostate-specific antigen (PSA) levels at diagnosis >20 mg/L (17.2% and 83.2%, respectively) (4). This is concordant with other studies that have characterized SSA men to have younger age at diagnosis, shorter PSA doubling time before surgery, higher prostatectomy Gleason scores, greater cancer volume, more advanced tumor stage and greater tumor volume per ng/mL of serum PSA (9,10). As demonstrated in a study of West African (Senegalese) men, the majority of African men had significantly worse oncologic outcomes, with more advanced disease, higher PSA, higher rates of symptomatic disease and higher percentage of metastatic disease at initial presentation compared with African-American and United States (U.S.) White men (11).

Despite this seemingly disproportionate burden and the prevailing challenges, it is still quite difficult to precisely describe the burden of CaP in SSA. Based on 2006 data available from the International Association of Cancer Registries, only 11% of the total population of Africa was covered by cancer registries, and the few existing registries often did not meet the accepted standards for population cancer registries (12-15). Furthermore, the burden of CaP could be underestimated due to lack of widespread availability of early diagnosis using PSA, digital rectal examination and biopsy services for accurate assessment of malignant or benign disease, weak health management information systems, misdiagnosis or delayed diagnosis, lack of access to healthcare, limited treatment options which leads to alternative medical practices, scarcity of expert care, and the high cost of treatment (16).

Strengthening cancer surveillance and treatment in this region is of the utmost importance and should be prioritized as the majority of SSA men present with aggressive disease and at a late stage with metastases. This results in treatment being used more frequently with palliative rather than curative intent. There is relatively limited information about CaP treatment, survival and management in SSA. While radical prostatectomy has been the gold standard for men with localized CaP in much of the world, this option is limited to places where there are trained surgeons to perform that operation and generally offered only to men who have localized disease at diagnosis. For patients in SSA with advanced disease, surgical castration as well as use of luteinizing hormone-releasing hormone (LHRH) analogues, bicalutamide and flutamide were reported, and only limited use of docetaxel (17). Androgen deprivation therapy (ADT) (including orchiectomy with or without antiandrogens) is also one of more commonly used treatments because of the much higher proportion of men with advanced disease. Other treatments include chemotherapy, external beam radiation therapy (EBRT) with or without adjuvant ADT or active palliative approaches. However, many of these therapies are not widely available in most African countries, and hence this has led to unfavorable outcomes as treatment options have to be adjusted according to what is available locally.

In a retrospective review of 79 men who presented with metastatic CaP to a tertiary care hospital in Nigeria between 2010–2015, progression-free survival (PFS) was reported as 26.8 months [95% confidence interval (CI): 19.1–28.9] and median overall survival (OS) was 40.3 months (95% CI: 24.3–49.7) (18). For men with metastatic CaP, ADT can provide symptom relief and improve survival. However, invariably the disease becomes resistant to hormone therapy, leading to development of metastatic castrate resistant prostate cancer (mCRPC). The data on outcomes of men with mCRPC in SSA is extremely limited. Dr. Bello also reported on a series of 48 men with castrate resistant prostate cancer (CRPC) managed at a single public tertiary care hospital in Nigeria between 2011–2015 (19). Median OS for men with CRPC in this group was 11 months (95% CI: 7.8–14.2), which is dismal compared with survivals reported in the USA and elsewhere. Of note, 83% of patients had urinary symptoms, 79% bothersome pains and 33% cord compression, indicating a very symptomatic population. All men had metastatic disease at the time they were determined to be castrate resistant. Only 31% of patients received docetaxel and 4% received novel hormone therapy drugs (1 abiraterone, 1 enzalutamide). For patients that received docetaxel chemotherapy, median OS was 17 months, vs. 8 months in those that did not (P=0.003), suggesting that availability of chemotherapy could provide valuable time to these patients (19).

Numerous therapeutic options which are not widely available to patients in SSA have been Food and Drug Administration (FDA) approved in the USA for mCRPC, including chemotherapy (docetaxel, cabazitaxel), radiopharmaceuticals [radium 223, prostate-specific membrane antigen (PSMA) radioligand], immunotherapy (sipuleucel-T), poly-ADP ribose polymerase (PAPR) inhibitors for men with specific mutations in their genomic analysis (olaparib, rucaparib) and newer generation hormone therapy (enzalutamide, abiraterone + prednisone, apalutamide, darolutamide). We discuss a summary of pertinent data related to these therapies and suggestions for which therapies are likely to provide the largest benefit to the largest number of patients with metastatic CaP if made widely available. Additional information on these therapies discussed are included in the Table S1.

Treatment

Chemotherapeutic options for mCRPC includes docetaxel, cabazitaxel, or a combination of one of these chemotherapy agents with next generation hormone therapy.

In terms of second-generation anti-androgens, abiraterone with prednisone (FDA approved in 2011 for patients with mCRPC following use of chemotherapy) has demonstrated benefit in median OS for patients with mCRPC (20). Indications later expanded in 2012 use prior to chemotherapy given trial data demonstrating not only survival benefit, but also delay in pain progression and improvement in quality of life (21). In 2018, abiraterone’s indication was expanded once again to include patients with metastatic castrate-sensitive prostate cancer (mCSPC) given improvements in OS, radiographic PFS, and pain management (22). Overall, the therapy has been proven to be well tolerated with notable side effects being hypertension and hypokalemia (22). Newer agents such as enzalutamide, apalutamide, and darolutamide also have demonstrated survival benefit for patients with metastatic CaP and are also well tolerated with very manageable side effects. These drugs have also been proven to be beneficial in a variety of disease settings including mCRPC pre-chemotherapy, post-chemotherapy and/or metastatic castrate sensitive CaP at time of initial diagnosis. Patients receiving these drugs have benefited not only in terms of survival, but also in quality-of-life measures including delay in pain progression (21,23).

More recent data has also demonstrated that triple therapy with docetaxel, next generation hormone therapy and LHRH analogues has potentially even greater efficacy. While the data is encouraging that more aggressive therapy at the initial diagnosis of metastatic disease can provide improved outcomes, it would be difficult to justify pursuing the combination of docetaxel and darolutamide upfront until either of these options were to be widely available to patients in SSA. Another class of drugs available for management of mCRPC is radiopharmaceuticals. Radium-223 is an alpha emitting radiopharmaceutical which was demonstrated to improve median OS in men with mCRPC. This therapy is a calcium mimetic, and specifically targets bone disease, thus limiting the efficacy to patients with bone predominant disease.

More recently, the beta emitting radioligand lutetium-177-PSMA-617, which delivers beta-particle radiation to cells that express PSMA, has demonstrated statistically significant improvement in OS in men with mCRPC that received at least one androgen receptor pathway inhibitor and one taxane chemotherapy and had positive PSMA scans. For this therapy to be considered, patients must first have evidence of PSMA expression on positron-emission tomography (PET) PSMA scans. Given the lack of widespread availability of these scans, usefulness in SSA is expected to be quite limited at this point.

In addition to advancements in hormone therapy, chemotherapy and radiopharmaceuticals, targeted therapy has proven benefit in management of patients with mCRPC. PARP inhibitors such as olaparib, rucaparib, talazoparib, niraparib have been beneficial for patients with specific deleterious or suspected deleterious homologous recombination repair gene. Much of the benefit is driven by patients with BRCA2 mutations, though clinical responses are also seen in patients with other DNA repair defect mutations. Benefit has been demonstrated with combination of PARP inhibitors and next generation oral hormonal agents as well. Approximately 12% of patients with metastatic CaP were found to have germline mutations in DNA repair genes, with 44% of those having BRCA2. This was in a predominantly non-Hispanic white population (24). The frequency of mutations in DNA repair pathway genes (somatic/germline) is up to approximately 30%, though approximately 11% BRCA1/2; again in a population not expected to be representative of SSA (25). Though PARP inhibitors have a well-established role in mCRPC at this time, molecular profiling is essential to patient selection, and this is currently not widely available in SSA. As such, focusing on making these drugs more widely available in SSA at this time is likely to not have high impact.

While the use of immunotherapy has revolutionized the treatment of many cancers, the role of immunotherapy is quite limited in CaP at this time. The only immunotherapy with demonstrated survival benefit in CRPC is sipuleucel-T. This immunotherapy is created from autologous peripheral-blood mononuclear cells that have been activated against a prostate antigen fused to an immune-cell activator. The treatment has been reported to be well tolerated overall but is quite complex to deliver, requiring three separate pheresis procedures followed by infusions 3 days later, with a strict time window. Given the difficulties with treatment delivery, the logistics do not seem feasible for administration in SSA at this time.

Although there is some consideration for programmed cell death 1 (PD-1) directed therapy in CaP, FDA approval is limited due to tissue agnostic use for advanced solid tumors that do not have other treatment options and are designated high levels of microsatellite instability (MSI-H) or deficient mismatch repair (dMMR). This applies to only a small minority of CaP patients, found to be approximately 3% in one series (26). Major toxicities of immunotherapy are related to risk of immune mediated toxicity which can present in a wide range of ways including pneumonitis, hepatitis, thyroiditis, colitis, dermatitis and lead to potential need for hospitalizations and high dose steroids. Though severe immune mediated toxicities are infrequent in patients on PD-1 directed therapies, the wide presentations of toxicities along with need for rapid intervention requires monitoring relatively extensive parameters at least every few weeks. This could be challenging in much of the SSA setting and would require significant training on management of these therapies prior to widespread use. As such, making immunotherapy more widely available for management of CaP in SSA is likely to have limited impact at this time.

Discussion

While the world has made advances in treatment of CaP, most of the potential therapeutic options do not seem to be widely available in SSA. Table S1 discusses some of these therapies in more detail, and we provided year of U.S. FDA approval to provide some context for how long some of these therapies have been available to men with CaP. We would argue that availability of abiraterone and prednisone may have one of the most meaningful impacts. Abiraterone is a well-tolerated drug which blocks synthesis of androgens and is given in combination with low dose prednisone for management of CaP, in both the castrate-sensitive and castrate resistant settings. As discussed above, the drug has demonstrated a remarkable benefit in management of advanced CaP, initially being approved in the castrate resistant (hormone refractory) metastatic setting and subsequently moving into the castrate sensitive (hormone sensitive) setting. While the drug has demonstrated benefit in castrate resistant setting pre and post chemotherapy, the most notable benefit has been seen in castrate sensitive setting when patients are initially diagnosed with metastatic CaP.

Cost continues to play a major role in access to care. Chemotherapy with docetaxel remains a reasonably affordable option; however, one would have to consider the need for trained staff, infusion center, and appointments. Abiraterone has been estimated to have the most reasonable costs compared to the alternative second-generation anti-androgens (Table S1). We included information about costs of advanced CaP therapies in the U.S., though the prices of these treatments are very variable as administration costs are not included in the estimates we provide. In addition, therapies have different cost implications depending on total cycles/length of therapy (radium 223 is limited to six treatments over 6 months, sipuleucel-T is limited to three treatments over 1 month, novel oral hormone therapies are given on ongoing basis often over years). We provided estimated costs for either a complete course of approved therapy or 1 year. Approximate costs were estimated based on Drugs.com and Medicare April 2024 Average Sales Price (ASP) pricing files using estimate of 70 kg man, 70 inches, body surface area (BSA) 1.87 m² (DuBois) (27).

This pricing listed is to give some sense of a scale of pricing difference between these therapies, and does not include cost of administration for intravenous (IV) therapeutics, nor cost of laboratory monitoring. Drug pricing is not transparent but has been demonstrated to be significantly higher in the USA compared with other countries (28,29). Based on verbal discussion with oncologists practicing in SSA, pricing of generic abiraterone expected to be likely up to several hundreds of dollars per month range, but not thousands.

Updated data from the STAMPEDE study demonstrated a median survival improvement of approximately 3 years with addition of abiraterone/prednisone to standard of care with ADT, median survival of 26 months with standard of care and 79 months with standard of care plus abiraterone/prednisone [hazard ratio (HR) 0.60, 95% CI: 0.50–0.71, P=0.31×10⁻⁹] (30).

When one compares this 79-month median survival with standard of care plus abiraterone/prednisone, the disparate survival of 40 months for newly diagnosed metastatic CaP in the Nigerian series discussed earlier is quite staggering.

Abiraterone and prednisone has been proven in several phase III clinical trials to provide significant survival benefit to patients in multiple phases of the disease. When one compares these benefits, it is clear that utilization of abiraterone/prednisone earlier in the course of metastatic disease, specifically when the disease is still sensitive to hormone therapy, appears to provide greatest benefit. Though enzalutamide and more recently apalutamide, also have proven benefit in the castrate sensitive metastatic CaP setting, abiraterone may be preferred for several reasons. As the first of the newer generation hormone therapies to become available, abiraterone has generic options available, with hopes of drops in price in the future. In addition, though the cost of abiraterone is significant, modifications to dosing could provide significant cost savings. The administration of this drug was studied in a fasting state, as drug exposure was demonstrated to increase when taken with food (31). A prospective international phase II study looked at low dose abiraterone 250 mg daily with a low-fat meal rather than standard dosing with 1,000 mg taken fasting. Effect on androgen levels and PSA kinetics was similar in both arms (32). The National Comprehensive Cancer Network (NCCN) guidelines have therefore included the 250 mg daily dose in their treatment options. Data suggests that the majority of medical oncologists in resource limited settings would consider this approach in order to improve access for patients to this therapy (33).

Use of abiraterone does require concomitant prednisone to address potential symptoms of mineralocorticoid excess which could include elevated blood pressure, low potassium levels and fluid retention. Monitoring of patients on abiraterone includes blood pressure, blood work including potassium and liver function tests, within initial assessments being every few weeks, but can be extended to longer intervals in follow up after a patient is stable on therapy for a few months. In the LATITUDE study, side effects reported included: hypertension (37% all grades, 20% grade 3–4), hot flush (15% all grades), hypokalemia (20% all grades), elevated aspartate transaminase/alanine transaminase (AST/ALT) (15–16% all grades, 4–5% grade 3–4) (package insert Janssen) (34). Overall, abiraterone and prednisone is a well-tolerated combination therapy with very manageable toxicities.

Conclusions

In summary, abiraterone and prednisone combination has a favorable and very manageable side effect profile, with a significant and clinically meaningful impact. The prioritization of abiraterone as a treatment option for patients with CRPC is also emphasized in the NCCN Harmonized Guidelines for Sub-Saharan Africa (version 2.2021). Though other options such as chemotherapy, targeted therapy, radiopharmaceuticals and immunotherapy also have meaningful and significant benefit, the absolute benefit of abiraterone as well as the ease of administration (favorable side effect profile, frequency of visits and monitoring) would favor an urgent prioritization to make this or similar newer generation hormone therapy available to patients in SSA as soon as possible.

The focus of this discussion has been on treatment options for management of metastatic CaP, though the authors recognize that early diagnosis and treatment in the curative setting is of utmost importance as well. While we hope for a future in which all potentially beneficial therapies are available to all patients across the globe, the focus at this time in limited resource settings needs to be on prioritizing the availability of therapies that would have the broadest impact first.

Acknowledgments

Funding: None.

Footnote

Peer Review File: Available at https://tcr.amegroups.com/article/view/10.21037/tcr-23-2289/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-23-2289/coif). P.V. reports that receiving grants or contracts from UICC for his department, as well as payment or honoraria from Roche, Novartis, and MSD, support for attending meetings and/or travel from Roche and MSD, and holding unpaid leadership or fiduciary role in WHO’s GBCI and ICF Foundation. T.M. reports that receiving grants or contracts from Merck, Sotio, and Curium as institutional funding for trial, as well as consulting fees from Blue Earth Diagnostics and IMPACT Network, payment for educational event from Aptitude Health, and serving on the advisory board of Exelexis. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Sharma K, Mayer T, Li S, et al. Advancing oncology drug therapies for sub-Saharan Africa. PLOS Glob Public Health 2023;3:e0001653. [Crossref] [PubMed]
2. Powell IJ. The precise role of ethnicity and family history on aggressive prostate cancer: a review analysis. Arch Esp Urol 2011;64:711-9. [PubMed]
3. Ngcamphalala C, Ostensson E, Hlongwa M, et al. Mapping evidence on the distribution of the costs associated with cancer of prostate, cervix, and female breast in the sub-Saharan Africa: protocol for a scoping review. Syst Rev 2021;10:113. [Crossref] [PubMed]
4. Hayes VM, Bornman MSR. Prostate Cancer in Southern Africa: Does Africa Hold Untapped Potential to Add Value to the Current Understanding of a Common Disease? J Glob Oncol 2018;4:1-7. [Crossref] [PubMed]
5. Seraphin TP, Joko-Fru WY, Kamaté B, et al. Rising Prostate Cancer Incidence in Sub-Saharan Africa: A Trend Analysis of Data from the African Cancer Registry Network. Cancer Epidemiol Biomarkers Prev 2021;30:158-65. [Crossref] [PubMed]
6. Ramaliba TM, Sithole N, Ncinitwa A, et al. Prostate Cancer Patterns and Trends in the Eastern Cape Province of South Africa; 1998-2017. Front Public Health 2022;10:882586. [Crossref] [PubMed]
7. Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893-917. [Crossref] [PubMed]
8. Bray F, Parkin DMAfrican Cancer Registry Network. Cancer in sub-Saharan Africa in 2020: a review of current estimates of the national burden, data gaps, and future needs. Lancet Oncol 2022;23:719-28. [Crossref] [PubMed]
9. Sanchez-Ortiz RF, Troncoso P, Babaian RJ, et al. African-American men with nonpalpable prostate cancer exhibit greater tumor volume than matched white men. Cancer 2006;107:75-82. [Crossref] [PubMed]
10. Babb C, Urban M, Kielkowski D, et al. Prostate cancer in South Africa: pathology based national cancer registry data (1986-2006) and mortality rates (1997-2009). Prostate Cancer 2014;2014:419801. Erratum in: Prostate Cancer 2014;2014:391257. [Crossref] [PubMed]
11. Gueye SM, Zeigler-Johnson CM, Friebel T, et al. Clinical characteristics of prostate cancer in African Americans, American whites, and Senegalese men. Urology 2003;61:987-92. [Crossref] [PubMed]
12. Parkin DM. The evolution of the population-based cancer registry. Nat Rev Cancer 2006;6:603-12. [Crossref] [PubMed]
13. Harvey N, Adeyoju A, Brough R. Prostate cancer in sub-Saharan Africa: diagnosis and management. In: Cancer in Sub-Saharan. Africa: Springer; 2017:95-107.
14. Rebbeck TR, Devesa SS, Chang BL, et al. Global patterns of prostate cancer incidence, aggressiveness, and mortality in men of african descent. Prostate Cancer 2013;2013:560857. [Crossref] [PubMed]
15. Jalloh M, Niang L, Ndoye M, et al. Prostate cancer in Sub Saharan Africa. J Nephr and Urol Res 2013;1:15-20.
16. Lewis DD, Cropp CD. The Impact of African Ancestry on Prostate Cancer Disparities in the Era of Precision Medicine. Genes (Basel) 2020;11:1471. [Crossref] [PubMed]
17. Cassell A, Yunusa B, Jalloh M, et al. Management of Advanced and Metastatic Prostate Cancer: A Need for a Sub-Saharan Guideline. J Oncol 2019;2019:1785428. [Crossref] [PubMed]
18. Bello JO. Predictors of survival outcomes in native sub Saharan black men newly diagnosed with metastatic prostate cancer. BMC Urol 2017;17:39. [Crossref] [PubMed]
19. Bello JO. Natural history of castration-resistant prostate cancer in sub-Saharan African black men: a single-centre study of Nigerian men. Ecancermedicalscience 2018;12:797. [Crossref] [PubMed]
20. Fizazi K, Scher HI, Molina A, et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol 2012;13:983-92. [Crossref] [PubMed]
21. Basch E, Autio K, Ryan CJ, et al. Abiraterone acetate plus prednisone versus prednisone alone in chemotherapy-naive men with metastatic castration-resistant prostate cancer: patient-reported outcome results of a randomised phase 3 trial. Lancet Oncol 2013;14:1193-9. [Crossref] [PubMed]
22. Fizazi K, Tran N, Fein L, et al. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med 2017;377:352-60. [Crossref] [PubMed]
23. Stenzl A, Dunshee C, De Giorgi U, et al. Effect of Enzalutamide plus Androgen Deprivation Therapy on Health-related Quality of Life in Patients with Metastatic Hormone-sensitive Prostate Cancer: An Analysis of the ARCHES Randomised, Placebo-controlled, Phase 3 Study. Eur Urol 2020;78:603-14. [Crossref] [PubMed]
24. Pritchard CC, Mateo J, Walsh MF, et al. Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer. N Engl J Med 2016;375:443-53. [Crossref] [PubMed]
25. Chung JH, Dewal N, Sokol E, et al. Prospective Comprehensive Genomic Profiling of Primary and Metastatic Prostate Tumors. JCO Precis Oncol 2019;3:PO.18.00283.
26. Abida W, Cheng ML, Armenia J, et al. Analysis of the Prevalence of Microsatellite Instability in Prostate Cancer and Response to Immune Checkpoint Blockade. JAMA Oncol 2019;5:471-8. [Crossref] [PubMed]
27. Centers for Medicare & Medicaid Services. ASP Pricing Files [Internet]. Baltimore (MD): Centers for Medicare & Medicaid Services; [cited 2024 Apr 20]. Available online: https://www.cms.gov/medicare/payment/part-b-drugs/asp-pricing-files
28. Janssen Daalen JM, den Ambtman A, Van Houdenhoven M, et al. Determinants of drug prices: a systematic review of comparison studies. BMJ Open 2021;11:e046917. [Crossref] [PubMed]
29. Mulcahy A, Whaley C, Gizaw M, et al. International prescription drug price comparisons. 2021 Jan. Available online: https://www.rand.org/pubs/research_reports/RR2956.html
30. James ND, Clarke NW, Cook A, et al. Abiraterone acetate plus prednisolone for metastatic patients starting hormone therapy: 5-year follow-up results from the STAMPEDE randomised trial (NCT00268476). Int J Cancer 2022;151:422-34. [Crossref] [PubMed]
31. Stuyckens K, Saad F, Xu XS, et al. Population pharmacokinetic analysis of abiraterone in chemotherapy-naïve and docetaxel-treated patients with metastatic castration-resistant prostate cancer. Clin Pharmacokinet 2014;53:1149-60. [Crossref] [PubMed]
32. Szmulewitz RZ, Peer CJ, Ibraheem A, et al. Prospective International Randomized Phase II Study of Low-Dose Abiraterone With Food Versus Standard Dose Abiraterone In Castration-Resistant Prostate Cancer. J Clin Oncol 2018;36:1389-95. [Crossref] [PubMed]
33. Patel A, Tannock IF, Srivastava P, et al. Low-Dose Abiraterone in Metastatic Prostate Cancer: Is It Practice Changing? Facts and Facets. JCO Glob Oncol 2020;6:382-6. [Crossref] [PubMed]
34. Fizazi K, Tran N, Fein L, et al. Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial. Lancet Oncol 2019;20:686-700. [Crossref] [PubMed]