Combination Treatment in Metastatic Prostate Cancer: Is the Bar Too High or Have We Fallen Short?

The established efficacy of several novel androgen receptor pathway inhibitors (ARPi) has dramatically improved the survival of patients with metastatic hormone sensitive prostate cancer (mHSPC), defining a new standard of care for these patients.¹

Similarly, where chemotherapy used to be reserved for castrate resistant disease, docetaxel has now expanded its indication and moved to the forefront in the armamentarium of treatment options for newly diagnosed mHSPC. Despite the mature body of evidence for upfront combination treatment in men with metastatic prostate cancer and attendant guideline recommendations, recent real-world studies have shown a glaringly low rate of adoption.

In this review,² besides reporting real-world data on treatment intensification practices from around the world, we delve into the various contributive factors that influence whether a patient ultimately receives the standard of care combination treatment.

Alarmingly, there is much variation in reimbursement times for new drugs amongst European countries which contributes in part to inequality in cancer care. This is demonstrated in the control arm of LATITUDE.³ As abiraterone was not provided by the trial in the CRPC setting, local access determined if control arm patients could benefit from abiraterone at progression. The difference of 8 months in OS between Eastern Europe where abiraterone was available and indicated for mCRPC compared to Western Europe which suffered from limited access provided evidence of the direct impact of differential drug access. Data from the Patient W.A.I.T. Indicator Survey in 2019 also alluded to the long-drawn process, with average time to reimbursements stretching as long as 504 days.⁴ Geographic and socio-economic differences also pose challenges as seen in rural areas. Report from the first global Prostate Cancer Consensus Conference for Developing Countries (PCCCDC) echoes the same concerns of resource limitation among clinicians in developing countries when faced with decision making.⁵ In the best practice setting, 64.9% of panelists voted for combination of ADT with abiraterone. This response drastically dropped to 8.1% when considering a setting of limited resources. The responses also swung in favour of ADT by orchiectomy alone and ADT combination with docetaxel purely from the perspective of cost in a setting of limited resources. In the same vein, when resources are limited, the availability of biomarkers to guide treatment selection in those who would benefit the most from treatment intensification would help improve the physician’s uptake of this new standard however this granularity in treatment selection is still lacking, and could hinder widespread adoption of combination treatment.

Written by: Kenneth Chen, MBBS, MRCS, MCI, DFD, FRCS, FAMS, Consultant Urologist, Singapore General Hospital, Clinical Assistant Professor, Duke-NUS Graduate Medical School, Singapore, Clinical Lecturer, YLL School of Medicine, Singapore

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Combination Treatment in Metastatic Prostate Cancer: Is the Bar Too High or Have We Fallen Short? - Kenneth Chen

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