ASCO GU 2023: How to Best Use Current Drugs: Treatment Sequencing and Combinations for Metastatic Castration-Resistant Prostate Cancer

( The 2023 GU ASCO annual meeting included a session on advanced prostate cancer, specifically new targets, new drugs, and new victories, featuring a presentation by Dr. Silke Gillessen discussing treatment sequencing and combinations for metastatic castration-resistant prostate cancer (mCRPC). Dr. Gillessen started her presentation by highlighting the current landscape for systemic therapies for mCRPC based on lines of therapy:


Indeed, several agents are approved for mCRPC, but the “best use” is unclear. Most control arms are not current standard therapy, most patients included are not treated with combination treatment for mHSPC, with the goal of trying to offer as many of the therapies as possible and the decision starting in the mHSPC disease space. Dr. Gillessen notes that there are different scenarios at this time for starting first-line mCRPC based on a patient’s prior therapies:

  1. ADT alone for mHSPC
  2. ADT plus docetaxel for mHSPC
  3. ADT plus ARPI for mHSPC
  4. ADT plus docetaxel + ARPI for mHSPC

With regards to scenarios 1 and 2 (ADT or ADT + docetaxel for mHSPC) Dr. Gillessen notes that most patients will receive abiraterone or enzalutamide for first-line mCRPC. However, the question remains: should we add or not add a PARP inhibitor? Should this be considered in selected patients only? There is an abundance of data at this meeting with regard to this question, specifically the final OS analysis of PROpel, TALAPRO-2, and updates from MAGNITUDE. A possible treatment algorithm for scenario 1 is as follows:

ASCO GU Gillessen-1.jpg

A possible treatment algorithm for scenario 2 is as follows:

ASCO GU 2023 Gillessen.jpg

With regards to situation 3, ADT + ARPI for mHSPC, the question is docetaxel or PARP inhibitor for patients with BRCA alterations for first-line mCRPC. At the APCCC 2022 meeting, when this question was asked, the most common answer was PARP inhibitor (75%). Based on results from this meeting, the TRITON-3 trial1 now has data in this disease space:

ASCO GU 23 TRITON-3 trial.jpg 

A possible treatment algorithm for scenario 3 is as follows:

TRITON-3 trial.jpg

Finally, a possible treatment algorithm for scenario 4 is as follows:

 ASCO TRITON-3 trial.jpg

Dr. Gillessen concluded her presentation by discussing treatment sequencing and combinations for mCRPC with the following take-home messages:

  • This is a dynamic landscape
  • The best option is to include patients in trials
  • It is important to offer all potential options to a patient “in time”
  • Few selected patients can benefit from immune checkpoint inhibitors (MSI high, CDK12 mutations)
  • The best use of radium-223 is unclear
  • We must not forget bone targeted agents

Presented by: Silke Gillessen, MD, Oncological Institute of Southern Switzerland, Bellinzona, Switzerland

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2023 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, Thurs, Feb 16 – Sat, Feb 18, 2023. 


  1. Fizazi K, Piulats JM, Reaume MN, et al. Rucaparib or Physician’s Choice in Metastatic Prostate Cancer. N Engl J Med. 2023 Feb 16 [Epub ahead of print].