Post-docetaxel options for further survival benefit in metastatic castration-resistant prostate cancer: Questions of choice

Abstract

There are currently two medical treatments approved in Canada that offer survival benefits for patients with metastatic castrationresistant prostate cancer that progresses on or after docetaxel-based chemotherapy, and evidence is accumulating on the efficacy of further interventions in this setting. The current and emerging strategies are based on a variety of mechanisms (cytotoxicity, hormonal inhibition, radiopharmacy and immunotherapy) and there is nothing to suggest that patients will be unable to benefit from several or even all of these agents when used sequentially. Given the possibility of multiple lines of treatment for patients whose disease progresses on or after docetaxel, the challenge for clinicians will be to determine the optimum treatment pathway for each individual. That challenge is already being faced, albeit on a limited scale, now that both cabazitaxel (chemotherapy) and abiraterone (hormonal agent) are available for use post-docetaxel. IntroductionAs recently as the beginning of the 21st century, metastatic castration-resistant prostate cancer (mCRPC) had a bleak prognosis. The available treatments, such as radiotherapy, boneseeking isotopes, bisphosphonates, chemotherapy, corticosteroids and analgesics, offered palliation of symptoms, but no improvement in survival. 1 In the past 8 years, the outlook has changed dramatically. First, the landmark TAX327 trial of docetaxel demonstrated that, contrary to previous experience, 2 mCRPC was responsive to chemotherapy in terms of patient survival.1 Then, in 2010, after 6 years with no treatment offering a survival benefit in the post-docetaxel setting, phase III data on cabazitaxel showed that patients could derive further survival benefit from second-line chemotherapy.3 In 2011, the hormonal agent abiraterone was also reported to improve survival in patients previously treated with docetaxel. 4 Both cabazitaxel and abiraterone are now approved for use in Canada for the treatment of mCRPC that has progressed during or after docetaxel-based chemotherapy. In addition, evidence is accumulating from trials of other agents, not yet approved in Canada, that offer a survival benefit in mCRPC.With these ongoing therapeutic developments, the multidisciplinary team caring for men with mCRPC has a growing choice of agents to use in the post-docetaxel setting. The recent and emerging treatments vary widely in their mode of action (cytotoxicity, hormonal inhibition, radiopharmacy, immunotherapy), and there is no suggestion, to date, that patients will be able to benefit from only one of the postdocetaxel options. Indeed, the possibility has been mooted of mCRPC entering an age of chronic-disease-style management, with an array of treatments, each improving the survival of the individual.5 Even with the choice narrowed to the two agents currently approved for use post-docetaxel, it is anticipated that patients will be able to derive a survival advantage from both cabazitaxel and abiraterone. 6 The key question for clinicians and their patients is: how ...

Optimal management of patients receiving cabazitaxel-based chemotherapy

“…S11]. 3,4 He responded well to the treatment-his PSA at the commencement of the trial was 88 µg/L, and reached a nadir of 13 µg/L in January 2010. Abiraterone was halted in November 2010 after the detection of significant disease progression, and the patient received a single dose of palliative radiotherapy to address pain in his left hip.…”

“…[1][2][3] There are also various other promising agents on the horizon. As discussed previously in this supplement on page S11), 4 rational sequencing of these agents is likely to play a pivotal role in ensuring optimal care for each individual patient. Another key factor is proactive management of side effects.…”

Chemotherapy for prostate cancer: Clinical practice in Canada

“…(The implications for the treatment pathway of advances in chemotherapy and other developments in the management of mCRPC are discussed by Asselah and Sperlich in this supplement on page S11. 22 )…”

Metastatic castration-resistant prostate cancer: The emerging continuum of care

“…6 There is discussion of how cabazitaxel and abiraterone, with their differing modes of action and side effect profiles, may play a role in the management of mCRPC to optimize the overall outcome for patients. 6 The final article 7 discusses how the predictable cytotoxic side effects of cabazitaxel can be minimized and managed, enabling men with mCRPC who have already received docetaxel to have access to second-line chemotherapy as part of their treatment. The authors also provide real-life case studies to illustrate how cabazitaxel is being used in the Canadian clinical setting.…”

“…In this supplement, clinicians consider the evidence base for both of these new treatments, 5,6 and for treatments that may emerge into the mCRPC landscape in the near future. 6 There is discussion of how cabazitaxel and abiraterone, with their differing modes of action and side effect profiles, may play a role in the management of mCRPC to optimize the overall outcome for patients.…”