Dr Hussain on Key Ongoing Clinical Trials in Metastatic Castrate-Resistant Prostate Cancer

Maha Hussain, MD, FACP, FASCO, Genevieve E. Teuton Professor of Medicine, Division of Hematology-Oncology, Department of Medicine, and deputy director and leader of the GU Oncology Program, Robert H. Lurie Comprehensive Cancer Center of the Northwestern University Feinberg School of Medicine, discusses clinical trials evaluating therapeutics for patients with metastatic castrate-resistant prostate cancer (mCRPC).

Clinicians still need a better understanding of why mCRPC progresses, because that will inform which pathways therapies should be developed for, Hussain begins. There are several ongoing clinical trials of interest, some of which are overlapping, Hussain continues. Studies are underway examining strategies such as PARP inhibition, AR inhibition, and radioligand therapy, Hussain explains.

Notable ongoing studies in mCRPC include the phase 2 BRCAAway trial (NCT03012321) and the phase 3 CONTACT-2 trial (NCT04446117). In the randomized BRCAAway study, investigators are comparing abiraterone acetate (Zytiga)/prednisone with olaparib (Lynparza) and with abiraterone/prednisone plus olaparib in patients with mCRPC with ATM, BRCA1 and/or BRCA2 mutations, deletions, or loss of heterozygosity. Findings presented at the 2024 Genitourinary Cancers Symposium (ASCO GU) demonstrated that abiraterone/prednisone plus olaparib was well tolerated and resulted in an extended progression-free survival (PFS) compared with either agent alone or sequential therapy.

In CONTACT-2, investigators are evaluating cabozantinib (Cabometyx) plus atezolizumab (Tecentriq) vs second novel hormonal therapy in patients with mCRPC following progression on first novel hormonal therapy. Findings from CONTACT-2, which were also presented at ASCO GU, demonstrated that the combination significantly improved PFS vs second novel hormonal therapy in patients with mCRPC with extrapelvic nodal or visceral disease.

Studies of combination therapies are also of interest, Hussain notes. Additionally, there is a lot of work being done to move effective treatments into the hormone-sensitive space, Hussain says. This is often where there is the best chance to combat the cancer cells because the tumor has not developed resistance yet, Hussain explains. The hope is that data in the mCRPC space develop quickly, and new therapies and combinations will emerge in the near future, Hussain concludes.