According to the CHAARTED1 and LATITUDE2 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 trial3. No OS benefit for the 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 study4 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):
The next topic discussed was the comparison of toxicities between docetaxel and abiraterone (Table 2).
Figure 2 – Comparison of toxicities between docetaxel and abiraterone:
Dr. Higano then provided some guiding tips for therapy selection in MHSPC patients:
1. Factors favoring ADT + docetaxel or abiraterone
- High volume, denovo presentation
- 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
- Patients prefer oral to IV route, or unfit for chemotherapy
- Pre-existing neuropathy
- Low volume disease
- 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
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