ASCO 2018: Balancing Toxicities, and Therapeutics Perspective

Chicago, IL (UroToday.com) Celestia Higano, MD, gave an excellent talk on the topic of treatment toxicities in patients with metastatic hormone-sensitive prostate cancer (MHSPC). Dr. Higano began with the most important question in this topic, on how to decide which therapy to use in MHSPC. One of the options is to decide by volume of metastatic disease. 

According to the CHAARTED [1] and LATITUDE [2] studies patients with high volume disease should be given ADT plus docetaxel or abiraterone. 

For patients with low volume disease - ADT + abiraterone should be given. The addition of abiraterone for M1 and N1M0 disease increased the overall survival (OS) according to the STAMPEDE trial [3]. No OS benefit for addition of docetaxel to ADT alone was seen in the CHAARTED study.

The next question to be answered is if all patients with MHSPC need to be treated with ADT in combination with either docetaxel or abiraterone. In the SWOG 9346 study [4] OS in patients treated with ADT was based on PSA level, demonstrating a clear advantage to patients with PSA <=0.2 ng/ml, compared to patients with PSA >4 ng/ml (Figure 1). From this Dr. Hignao deducts that low-risk patients should be treated with ADT + / - abiraterone, and intermediate and high-risk patients should be treated with ADT + abiraterone or docetaxel.

Figure 1: Overall survival by PSA status after 7 months ADT (SWOG 9346):
OS PSA status 7 month ADT
The next topic discussed was the comparison of toxicities between docetaxel and abiraterone (Table 2). 

Figure 2 – Comparison of toxicities between docetaxel and abiraterone:
Docetaxel Abiraterone Toxicities
Dr. Higano then provided some guiding tips for therapy selection in MHSPC patients:

1. Factors favoring ADT + docetaxel or abiraterone
  • High volume, denovo presentation
2. Factors favoring ADT + docetaxel:
  • 18 weeks therapy vs. continuous therapy with abiraterone and prednisone (33 months)
  • Difficulty swallowing medications or taking on empty stomach
  • Poor diabetic control
  • Other contraindications for prednisone
  • Hear failure or hypervolemia
3. Factors favoring ADT + abiraterone and prednisone:
  • Patients prefer oral to IV route, or unfit for chemotherapy
  • Pre-existing neuropathy
  • Low volume disease
4. Factors favoring ADT + / - bicalutamide:
  • Low volume, recurrent disease, older patients
  • Excellent PSA response to ADT after 7 months, especially with low volume metastasis
  • Unfit for docetaxel or abiraterone
  • High degree of comorbidities
  • Cost
Dr. Higano concluded her interesting talk with some important take-home messages. For men with high volume disease – therapy should consist of ADT + docetaxel or abiraterone or ADT alone. For men with low volume disease – therapy should consist of ADT alone or with abiraterone. Therapy should also be chosen based on patient comorbidities, treatment-related toxicities, and patient preferences. Finally, there is still much to be learned on how the earlier use of docetaxel or abiraterone will impact downstream effects on the response in metastatic castrate-resistant prostate cancer.

References:
1. Sweeney CJ et al. NEJM 2015; 373(8):737-746
2. Fizazi K, et al. NEJM 2017l 2017; 377 (4):352-360
3. James ND, et al. NEJM 2017; 377(4) 339-351
4. Hussain M et al.  JCO, 2006:24(24):3984-3990

Presented by: Celestia Higano, MD, University of Washington


Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, Twitter: @GoldbergHanan at the 2018 ASCO Annual Meeting - June 1-5, 2018 – Chicago, IL USA
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