The safety assessment indicated, however, that patients experienced lower rates of adverse events (AEs) with C20 vs C25. Serious treatment-emergent AEs occurred in 30.5% of patients receiving C20 and 43.2% of patients receiving C25. David L. Graham, MD, of the Levine Cancer Institute in Charlotte, North Carolina, and an associate editor for the American Society of Clinical Oncology (ASCO) University Editorial Board, notes that these results may expand use of cabazitaxel: “we previously would hesitate to use it in men with a performance status of 2 or more. This report includes a breakout of that subset and states that treating them with 20 is manageable.”

Questions remain about the optimal use of C20 vs C25 in this patient population. Although C20 was non-inferior to C25 in the ITT group, the median OS was about 1 month shorter than with C25. In an accompanying editorial, Tian Zhang, MD, and Andrew J. Armstrong, MD, of the Duke University Medical Center in Durham, North Caroline, concluded that “physicians can feel comfortable using the…approved dose of C25 every 3 weeks for fit men” with aggressive disease, and that “it is reasonable to start at the lower C20 dose in men at increased risk of toxicity, given the similar survival rates and similar PFS [progression-free survival] and rates of pain palliation over time.”2

Dr Eisenberger noted that PROSELICA was not designed to investigate which types of patients should receive the reduced dose. “In my opinion, for men that have received extensive prior therapy, including extensive radiation to bone marrow, the options are dose reduction from C25 to C20 or administration of C25 plus growth factors. If hematological toxicity — which is the most important dose-limiting toxicity — persists, then dose reduction should be an option, even with growth factors.”

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Dr Graham, who was not involved in the study, said “I don’t see PROSELICA leading to the generalized use of C20 as a starting dose, but it does increase my comfort that dose reducing when toxicity warrants can be done without a significant loss of activity. Oncologists should consider using C20 in men who previously were considered possibly too fragile for treatment and should feel comfortable with dose reducing from C25 to C20 when need be. They can re-assure their patients that no significant loss of activity will likely be seen.”

The American Cancer Society estimates that over 161,000 cases of prostate cancer overall will be diagnosed in 2017.6 It is the third leading cause of cancer-related death in American men, with 26,730 men expected to die of the disease this year. The 5-year survival rate for men diagnosed with early-stage disease is over 99%, but drops to 29% for men with distant metastases.

As many patients are older or in fragile health states, limiting treatment toxicity is an important consideration. Dr Eisenberger’s takeaway from the recently available data suggests a bigger role for cabazitaxel in the future: “cabazitaxel is an active drug for mCRPC and, if one examines the data from the FIRSTANA study, one can argue that cabazitaxel could even be a good choice for first-line treatment.”

References

  1. Eisenberger M, Hardy-Bessard AC, Kim CS, et al. Phase III study comparing a reduced dose of cabazitaxel (20 mg/m2) and the currently approved dose (25 mg/m2) in postdocetaxel patients with metastatic castration-resistant prostate cancer—PROSELICA. J Clin Oncol. 2017 Aug 15. doi: 10.1200/JCO.2016.72.1076
  2. Clinical practice guideline in oncology: prostate cancer, version 2.2017. National Comprehensive Cancer Network website. https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf. Updated February 21, 2017. Accessed September 6, 2017.
  3. De Bono JS, Oudard S, Ozguroglu M, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010;376:1147-54.
  4. Zhang T, Armstrong A. The who, what, and how of cabazitaxel treatment in metastatic castration-resistant prostate cancer. J Clin Oncol. 2017 Aug 15. doi: 10.1200/JCO.2017.74.7931 [Epub ahead of print]
  5. Oudard S, Fizazi K, Sengeløv L, et al. Cabazitaxel versus docetaxel as first-line therapy for patients with metastatic castration-resistant prostate cancer: a randomized phase III trial—FIRSTANA. J Clin Oncol. 2017 Jul 28. doi: 10.1200/JCO.2016.72.1068 [Epub ahead of print]
  6. Cancer facts & figures, 2017. American Cancer Society website.  https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2017/cancer-facts-and-figures-2017.pdf. Accessed September 6, 2017.