Darolutamide Does Not Affect Cabazitaxel Systemic Exposure in mCRPC

Stefan Buck, MD, PhD

Cabazitaxel (Jevtana) can safely be combined with darolutamide (Nubeqa) in patients with metastatic castration-resistant prostate cancer (mCRPC), according to pharmacokinetic data from a study presented at the 2022 ASCO Annual Meeting.¹

Specifically, darolutamide was not found to affect cabazitaxel systemic exposure, justifying the use of the regimen, according to Stefan Buck, MD, PhD, of Erasmus MC Cancer Institute in Rotterdam, the Netherlands, and colleagues.

In describing the background for the study, the authors explained that “there is mounting evidence that addition of an androgen receptor [AR] signaling inhibitor improves taxane efficacy in prostate cancer.”^2,3 One of the studies concluded that simultaneous blocking of androgen receptor signaling with enzalutamide [Xtandi] improves efficacy of cabazitaxel, with the authors writing, “These findings support clinical studies that combine AR targeted inhibitors with cabazitaxel in CRPC.”²

However, the authors of the current study noted in their poster that “Drug-drug interactions may hamper these beneficial effects.”

In this study, investigators evaluated patients with mCRPC who were treated with cabazitaxel alone at 20 mg/m² every 3 weeks and with cabazitaxel plus darolutamide at 600 mg twice daily for 6 weeks. Cabazitaxel exposure was measured on day 1 and after 6 and 12 weeks of treatment with darolutamide using Area Under the Curve from 0 to 24 hours (AUC_0-24h).

The investigators found that cabazitaxel systemic exposure in 18 patients after 6 weeks of treatment with darolutamide was not significantly different compared to prior to darolutamide treatment (AUC_0-24h: –4%; 95% CI, –19 – +13%; P =.58). In addition, following 12 weeks of treatment with darolutamide, cabazitaxel systemic exposure was unaltered (AUC_0-24h: +4%; 95% CI, –10 – +20%; P = .54).

“Darolutamide, unlike enzalutamide, does not affect cabazitaxel systemic exposure, justifying their use in combination,” the authors wrote in their poster. For future directions for research, they suggested “a randomized phase 2 study on cabazitaxel plus or minus darolutamide in patients previously treated with a novel androgen receptor signaling agent.”

References

1. Buck S, Guchelaar NAD, de Bruijn P, et al. Influence of darolutamide on cabazitaxel systemic exposure. J Clin Oncol. 2022;40(suppl 16):5038. doi:10.1200/JCO.2022.40.16_suppl.5038
2. Smith MR, Hussain M, Saad F. Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med. 2022;386(12):1132-1142. doi:10.1056/NEJMoa2119115
3. Mout L, van Royen ME, de Ridder C, et al. Continued androgen signalling inhibition improves cabazitaxel efficacy in prostate cancer. EBioMedicine. 2021;73:103681. doi:10.1016/j.ebiom.2021.103681