Data Support Safe Interaction of Darolutamide and Cabazitaxel in mCRPC

Unlike with enzalutamide, it appears darolutamide does not affect systemic exposure of cabazitaxel in patients with metastatic castration-resistant prostate cancer.

Effects of darolutamide (Nubeqa) do not appear to influence systemic exposure of cabazitaxel (Jevtana), justifying their potential future use in combination for the treatment of metastatic castration-resistant prostate cancer, according to data presented in a poster at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.1

In describing the background for the study, the authors explained that “there is mounting evidence that addition of an androgen receptor signaling inhibitor improves taxane efficacy in prostate cancer.”2,3 One of the studies spotlighted showed 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, “Drug-drug interactions may hamper these beneficial effects.”

For the current study, investigators led by Stefan Buck, MD, PhD, of Erasmus MC Cancer Institute in Rotterdam, the Netherlands, evaluated patients with metastatic castration-resistant prostate cancer who were treated with cabazitaxel alone (20 mg/m2 every 3 weeks) and with cabazitaxel and darolutamide (600 mg twice daily) for 6 weeks. They measured cabazitaxel exposure on day 1 and after 6 and 12 weeks of treatment with darolutamide using area under the curve from 0 to 24 hours (AUC0-24h).

The investigators found that cabazitaxel systemic exposure in 18 patients after 6 weeks of treatment with darolutamide was not significantly different compared with prior darolutamide treatment (AUC0-24h, –4%; 95% CI, –19 –to 13%; P = .58). In addition, following 12 weeks of treatment with darolutamide, cabazitaxel systemic exposure was unaltered (AUC0-24h, 4%; 95% CI, –10 to 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