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A new study examines the combination of olaparib and abiraterone in treating metastatic castration-resistant prostate cancer, suggesting possible benefits and implications for patient selection and treatment strategies.

  • The PROpel trial explores the use of olaparib and abiraterone as first-line treatment for metastatic castration-resistant prostate cancer.
  • Combination therapy shows longer progression-free survival compared to hormonal treatments alone.
  • The lack of mature overall survival data, higher complication rates, and increased healthcare costs are potential limitations of combination therapy.
  • Further research is necessary to evaluate the benefits for specific patient groups and establish definitive conclusions.

PROpel Trial and the Use of Combined Therapy

The PROpel trial recently examined the use of olaparib and abiraterone, in addition to androgen deprivation therapy (ADT), for patients with metastatic castration-resistant prostate cancer (mCRPC) who had not received any first-line treatment. The results showed longer progression-free survival (PFS) for patients receiving the combination therapy compared to those using abiraterone alone. However, overall survival did not reach a significant threshold, necessitating further investigation in the current mCRPC treatment landscape.

Network Meta-Analysis of Randomized Controlled Trials

To put the PFS benefit seen in the PROpel trial in context, a systematic review and network meta-analysis (NMA) on first-line treatments for mCRPC was conducted and published in the journal European Urology Open Science. The trials compared novel hormonal treatments, such as abiraterone and enzalutamide, with poly (ADP-ribose) polymerase (PARP) inhibitors. The analysis included the PROpel, PREVAIL, and COU-AA-302 trials, comparing combination therapy to abiraterone or enzalutamide alone. The results showed a progression-free survival (PFS) benefit with combination therapy.

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Limitations and Further Research

While the combination therapy demonstrated a PFS benefit, there were some limitations. The PROpel trial was powered only for PFS, meaning a better overall survival signal in favor of combination therapy cannot be assumed. Moreover, the clinical benefit in terms of months of PFS “gained” seems limited and comes at the expense of higher toxicity and healthcare costs.

Further complicating the analysis, the MAGNITUDE trial showed a PFS benefit for combination therapy in a subgroup analysis for patients with alterations in HRR-associated genes, but not for unselected individuals. Similarly, the TALAPRO-2 trial demonstrated a PFS benefit and a trend towards better overall survival.

Conclusions and Implications

Given the current data, combining treatments may not be justified for all mCRPC patients. However, the benefit for specific cases, such as individuals with HRRm or a high metastatic burden, should be further evaluated. Mature overall survival data are needed before any definitive conclusion can be drawn regarding the potential role of combined olaparib and abiraterone as first-line treatment for mCRPC.

Source:

Fallara, G., Robesti, D., Raggi, D., Montorsi, F., Necchi, A., Cooperberg, M. R., Malavaud, B., Ploussard, G., & Martini, A. (2023). Contextualizing Olaparib and Abiraterone in the Current Treatment Landscape for Metastatic Castration-resistant Prostate Cancer. European Urology Open Science, 52, 40–43. https://doi.org/10.1016/j.euros.2023.03.009