The 2023 ASCO Annual Meeting presented groundbreaking research with the potential to reshape the first-line treatment landscape for metastatic castration-resistant prostate cancer (mCRPC). Two key studies, TALAPRO-2 (abstract 5053) and PROpel (abstract 5012), offer promising new combination therapies. This article explores the findings of these trials, along with expert perspectives from oncology pharmacists on their potential impact on patient care.
Prostate cancer cells. | Image credit: Kateryna Kon – stock.adobe.com
TALAPRO-2: Talazoparib and Enzalutamide Combination Therapy
The TALAPRO-2 trial investigated the efficacy and safety of talazoparib (Talzenna), a PARP inhibitor, in combination with enzalutamide (Xtandi) compared to enzalutamide plus placebo in patients with mCRPC. The study, a double-blind, randomized, placebo-controlled phase 3 trial, demonstrated a significant improvement in radiographic progression-free survival (rPFS) for the combination arm.
While this combination is currently under FDA review and poised to become a valuable treatment option, experts emphasize the importance of patient selection. Jamie K. Joy, PharmD, community site pharmacy operations manager at Fred Hutchinson Cancer Center, highlights the potential for increased toxicity, especially anemia, commonly associated with PARP inhibitors. The added pill burden and financial considerations are also crucial factors to consider.
Rebecca Tombleson, PharmD, BCOP, board certified oncology pharmacist, expresses concern about the high discontinuation rate (90%) observed in the trial, primarily due to anemia requiring transfusions. While acknowledging the benefits of an oral regimen, she stresses the need for careful monitoring and management of anemia, which can necessitate increased clinic visits and added costs associated with transfusions and supportive care.
Veronica Ajewole, PharmD, BCOP, notes the importance of coordinating care for patients requiring transfusions, particularly those accustomed to the convenience of oral oncolytics. She also emphasizes the crucial difference in talazoparib dosing for prostate cancer (0.5 mg) compared to breast cancer (1 mg), a vital detail for pharmacists to avoid medication errors. Dose reductions to 0.35 mg may be necessary based on weight and renal function.
PROpel Trial: Abiraterone and Olaparib Combination Therapy
The PROpel trial evaluated the combination of abiraterone (Zytiga) and olaparib (Lynparza) in patients with mCRPC and homologous recombination repair (HRR) gene mutations. The study’s positive results led to FDA approval of this combination just before the ASCO meeting, with compendium support from managed care.
While demonstrating improved outcomes, experts caution about the cost implications of combination therapy and the potential for anemia. Joy notes that although quality of life measures didn’t show significant differences between treatment arms, the financial burden and potential for anemia-related complications should be factored into treatment decisions. The value of this combination is particularly clear in patients with BRCA mutations, while decisions for other patient populations require careful consideration.
The PROpel trial’s inclusion of pain assessments is commended for its real-world relevance. However, the subjective nature of pain reporting and the increased opioid use observed in the treatment arm raise important considerations.
Conclusion
The TALAPRO-2 and PROpel trials offer promising new treatment options for mCRPC, expanding the therapeutic landscape with targeted combination therapies. However, careful patient selection, meticulous monitoring, and consideration of potential adverse events, including anemia, are crucial for optimizing patient outcomes. Furthermore, the financial burden of these therapies should be addressed to ensure equitable access to these advancements. Consulting with a healthcare professional is essential for personalized treatment plans and informed decision-making.
