Highlights on prostate cancer

Professor Bertrand Tombal, affiliated as a urologist at Cliniques Universitaires Saint-Luc in Brussels, provides updates on the proceedings of the ASCO GU 2024.

The GETUG-AFU 18 is a French study comparing 70 to 80 Gy radiation in patients with high-risk prostate cancer. Preliminary analysis of toxicity revealed no significant increase favouring the 80 Gy dosage. The oncological outcome, as assessed by bcPFS at 5 years, demonstrated rates of 91% and 88% for 80 Gy and 70 Gy, respectively. At 7 years, the respective rates were 88% and 79%. Despite these findings, considerable debate ensued regarding the therapeutic advantages of employing 80 Gy, with consensus indicating that it should not be regarded as the standard of care but rather evaluated on a case-by-case basis.

The BRACAAway trial, though of a modest scale, compared abiraterone, olaparib, and their combination in mCRPC patients harboring BRCA1/2 mutations, with no prior PARPi treatment. This study is of importance as the combination of abiraterone and olaparib is to be approved in Belgium for the PROpel indication. Nevertheless, uncertainties persist regarding its reimbursement, particularly for patients lacking BRCA1/2 mutations. The trial underscored the superiority of the combination over individual agents, even when considering potential second-line treatments. This marks the first clinical trial to elucidate the synergistic potential of abiraterone and olaparib, rendering it a pivotal publication with clinical implications irrespective of regulatory approval.

Lastly, the CONTACT-02 study explored the efficacy of cabozantinib in combination with atezolizumab in mCRPC patients who had progressed following prior NHT. While previous attempts at immunotherapy in mCRPC patients have yielded suboptimal results, this study indicated an increased PFS with the combination of cabozantinib and atezolizumab. However, OS data remain inconclusive due to the immature nature of the dataset. Notably, the efficacy of cabozantinib as monotherapy was comparable, prompting questions about the added value of incorporating atezolizumab, which currently lacks compelling evidence to reignite interest in immunotherapeutic agents. This study reiterates the benefits of cabozantinib but also underscores its challenging toxicity profile, even when compared to standard docetaxel therapy.

References:

Hennequin C, 2024, Long-term results of dose escalation (80 vs 70 Gy) combined with long-term androgen deprivation in high-risk prostate cancers: GETUG-AFU 18 randomized trial. J Clin Oncol 42, suppl 4; abstr LBA259

Hussain MHA, 2024, BRCAAway: A randomized phase 2 trial of abiraterone, olaparib, or abiraterone + olaparib in patients with metastatic castration-resistant prostate cancer (mCRPC) bearing homologous recombination-repair mutations (HRRm). J Clin Oncol 42, suppl 4; abstr 19)

Agarwal N, 2024, CONTACT-02: Phase 3 study of cabozantinib (C) plus atezolizumab (A) vs second novel hormonal therapy (NHT) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol 42, suppl 4; abstr 18)

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