Optimizing the Treatment of Metastatic Castration-resistant Prostate Cancer in Latin America: Incorporating New Evidence - Beyond the Abstract
At the 2017 American Society of Clinical Oncology (ASCO) annual meeting, we saw the presentation and simultaneous publication of two trials that tested the incorporation of abiraterone into standard treatment regimens for metastatic castration-sensitive disease: LATITUDE2 and STAMPEDE.3 This has been followed by the approval of this drug in many countries, in particular for the treatment of de novo metastatic high-risk prostate cancer. This stage of prostate cancer is particularly common in Latin America and Asia, where the majority of men do not undergo prostate-specific antigen screening. When abiraterone becomes more widely available, patients progressing to castration-resistance will also have an abiraterone-resistant cancer, with all the molecular alterations that this implies. In such patients, there will also most likely be cross-resistance to other agents, as previously shown by many groups, and as a consequence, the efficacy of enzalutamide or other approved hormonal therapies is likely to be diminished. Thus, chemotherapy and radium-223 will probably be better treatment choices for these men, given that their utility should not be affected by prior exposure to abiraterone. So, the sequencing of therapies in these patients will need to be reconsidered.
At the end of 2017, information became available about the combination of radium-223 and abiraterone in the ERA 223 trial. Although there has been no publication or formal presentation yet, it is clear that unexpectedly, the combination of these two agents causes more fractures. The reason for this is probably multifactorial, but these data perhaps point towards an important role in this setting for combinations which include bone protecting agents, such as zoledronic acid and denosumab. Such combinations are not as frequently used in Latin America as North America, due to the cost of the two medications. In Latin America, radium-223 is more frequently combined with estrogens or corticosteroids, as was done in the ALSYMPCA study.4 In this case, there are no special concerns about the safety of these combinations, but the use of concurrent bone protecting agents should nevertheless be strongly considered.
In February 2018, at the ASCO Genitourinary Cancers Symposium in San Francisco, results from two practice-changing trials in nmCRPC were presented, and in one case, were subsequently published (SPARTAN and PROSPER5). These results led to the approval of apalutamide, and the consideration of a label extension for enzalutamide in this setting. Again, these findings will affect treatment sequencing decisions, and will most likely result in more men progressing after intense hormonal blockade. Interestingly, an exploratory analysis of the SPARTAN trial data suggested that other new hormonal therapies, administered after discontinuation of apalutamide or placebo, might be more effective in patients who had previously received apalutamide.
In conclusion, several approved CRPC therapies are moving earlier within the disease continuum: chemotherapy first with the CHAARTED6 and STAMPEDE studies, abiraterone with LATITUDE and STAMPEDE studies, and now both enzalutamide and apalutamide for patients with nmCRPC. There is also preliminary evidence for the efficacy of radium-223 in the castration-sensitive setting. These rapid changes need to be adopted with caution. New combinations must be tested, and the consequences of the early use of more potent drugs further analyzed. In our article published in Medical Oncology, we reviewed the available data and guidance for the treatment of patients with metastatic CRPC, taking into account the factors that influence patient selection, the timing of treatment, and the best methods for treatment monitoring, and provided consensus recommendations from a Latin American perspective in order to assist physicians from this region in their clinical decision making.
In Latin America in particular, questions of cost and access will always be important. Something similar is happening with technology and the incorporation of new imaging modalities. This will cause stage migration and new classes of patients, molecularly and clinically speaking. Our recommendations still apply for the Latin American reality and they will continue to be relevant over an extended period of time and certainly will also need to be revisited periodically.
Fortunately for our patients with advanced prostate cancer, both prolongation of survival and improvement in the quality of their lives have been achieved. Our challenge is to bring all of these advances to Latin American patients and avoid past errors based on a lack of evidence-based information. Participating in clinical trials and working in collaboration is the best way to achieve precision medicine in prostate cancer in Latin America.
Written by: Juan Pablo Sade1 and Neal D Shore2
1. Instituto Alexander Fleming Buenos Aires, Argentina, Universitario Fundacion Santa Fe de Bogota, Bogota, Colombia
2. Carolina Urologic Research Center, Myrtle Beach, SC, USA.
References
1. Smith MR, Saad F, Chowdhury S, et al. Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. N Engl J Med 2018; 378: 1408-1418.
2. Fizazi K, Tran N, Fein L, et al. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med 2017; 377: 352-360.
3. James ND, de Bono JS, Spears MR, et al. Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. N Engl J Med 2017; 377: 338-351.
4. Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013; 369: 213-23.
5. Hussain M, Fizazi K, Saad F, et al. PROSPER: A phase 3, randomized, double-blind, placebo (PBO)-controlled study of enzalutamide (ENZA) in men with nonmetastatic castration-resistant prostate cancer (M0 CRPC). J Clin Oncol; 36: no.6_suppl (February 2018) 3-3.
6. Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med 2015; 373: 737-46.
Read the Abstract
Further Related Content:
First Presentation - PROSPER: Safety and Efficacy Study of Enzalutamide in Patients With Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC)
First Presentation - SPARTAN: A Study of Apalutamide (ARN-509) in Men with Non-Metastatic Castration-resistant Prostate Cancer