Expert Consensus Recommendations on the Management of Treatment-emergent Adverse Events Among Men with Prostate Cancer Taking Poly-ADP Ribose Polymerase Inhibitor + Novel Hormonal Therapy Combination Therapy.

Recent clinical trials have shown improvement in progression-free survival in men with metastatic prostate cancer (mPC) treated with combination poly-ADP ribose polymerase (PARP) inhibitors (PARPi) and novel hormonal therapy (NHT). Regulatory bodies in the USA, Canada, Europe, and Japan have recently approved this combination therapy for mPC. Common adverse events (AEs) include fatigue, nausea and vomiting, and anemia. Nuanced AE management guidance for these combinations is lacking. The panel objective was to develop expert consensus on AE management in patients with mPC treated with the combination PARPi + NHT.

The RAND/University of California Los Angeles modified Delphi Panel method was used. AEs were defined using the Common Terminology Criteria for Adverse Events. Twelve experts (seven medical oncologists, one advanced practice registered nurse, three urologists, and one patient advocate) reviewed the relevant literature; independently rated initial AE management options for the agent suspected of causing the AE for 419 patient scenarios on a 1-9 scale; discussed areas of agreement (AoAs) and disagreement (AoDs) at a March 2023 meeting; and repeated these ratings following the meeting. Second-round ratings formed the basis of guidelines.

AoDs decreased from 41% to 21% between the first and second round ratings, with agreement on at least one management strategy for every AE. AoAs included the following: (1) continue therapy with symptomatic treatment for patients with mild AEs; (2) for moderate fatigue, recommend nonpharmacologic treatment, hold treatment temporarily, and restart at a reduced dose when symptoms resolve; (3) for severe nausea or any degree of vomiting where symptomatic treatment fails, hold treatment temporarily and restart at a reduced dose when symptoms resolve; and (4) for hemoglobin 7.1-8.0 g/dl and symptoms of anemia, hold treatment temporarily and restart at a reduced dose after red blood cell transfusion.

This expert guidance can support management of AEs in patients with mPC receiving combination PARPi + NHT therapy.

A panel of experts developed guidelines for adverse event (AE) management in patients with metastatic prostate cancer treated with a combination of poly-ADP ribose polymerase inhibitors and novel hormonal therapy. For mild AEs, continuation of cancer therapy along with symptomatic treatment is recommended. For moderate or severe AEs, cancer therapy should be stopped temporarily and restarted at the same or a reduced dose when AE resolves.

European urology oncology. 2024 Jun 11 [Epub ahead of print]

Neal D Shore, Michael S Broder, Pedro C Barata, Tony Crispino, André P Fay, Jennifer Lloyd, Begoña Mellado, Nobuaki Matsubara, Nicklas Pfanzelter, Katrin Schlack, Paul Sieber, Andrey Soares, Hannah Dalglish, Alexander Niyazov, Saif Shaman, Michael A Zielinski, Jane Chang, Neeraj Agarwal

Carolina Urologic Research Center/GenesisCare, Myrtle Beach, SC, USA. Electronic address: ., PHAR (Partnership for Health Analytic Research), Beverly Hills, CA, USA., University Hospitals Seidman Cancer Center, Cleveland, OH, USA., Southwestern Oncology Group Cancer Research Network, UsTOO Prostate Cancer Support and Education, Las Vegas Chapter, NV, USA., PUCRS School of Medicine, Porto Alegre, Brazil., Huntsman Cancer Institute (NCI-CCC), University of Utah, Salt Lake City, UT, USA., Hospital Clínic de Barcelona, Catalonia, Spain., National Cancer Center Hospital East, Chiba, Japan., NorthShore University Health System, Evanston, IL, USA., Department of Urology, Prostate Center, University of Muenster Medical Center, Muenster, Germany., Keystone Urology Specialists, Lancaster, PA, USA., Hospital Israelita Albert Einstein, Sao Paulo, Brazil; Centro Paulista de Oncologia/Oncoclínicas, Sao Paulo, Brazil., Pfizer Inc, New York, NY, USA., Pfizer Inc, Collegeville, PA, USA.