(UroToday.com) In this presentation, Dr. de Bono summarized results of the IPATential150 trial, previously presented at ESMO 2020, which demonstrated an rPFS benefit for the combination of the AKT-inhibitor ipatasertib with abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC). This benefit was seen in the intention to treat population as well as when patients were stratified by PTEN expression status as defined by immunohistochemistry. PTEN loss was defined as more than 50% of viable malignant cells having no PTEN cytoplasmic staining using the SP218 PTEN immunohistochemistry antibody. The study design is summarized below. 

(UroToday.com) The CheckMate 9KD trial is a multi-arm open label phase 2 study evaluating the efficacy of the anti-PD-1 antibody nivolumab in combination with other therapies such as docetaxel, rucaparib or enzalutamide in metastatic castration-resistant prostate cancer (mCRPC). The rationale for the combination of nivolumab with docetaxel is that docetaxel is a standard of care therapy for mCRPC that may potentiate anti-tumor immune responses. Prior analysis of this combination at ESMO 2019 demonstrated a 37% overall response rate with one complete response and six partial responses. The study schema is shown below. The co-primary endpoints are overall response rate (investigator reports) and PSA response rate (>= 50% decrease). 

(UroToday.com) Immune checkpoint blockade using PD-1 and PD-L1 targeting agents has proven clinical benefit in many metastatic carcinomas. However, identification of patients most likely to benefit has been difficult with most predictive biomarkers examined to date (including PD-1/PD-L1 status and tumor mutational burden) failing to demonstrate clinical utility. CDKN2A is one of the most commonly altered genes across human cancers and offers the potential as a predictive biomarker. However, currently available data are conflicting with respect to the association between CDKN2A alterations and ICBs. Thus, in a poster presentation at the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU), Dr. Nassar and colleagues examine the effect of CDKN2A alterations on clinical outcomes in patients with urothelial carcinoma received immune checkpoint blockade (ICB). 

(UroToday.com) Platinum-based cytotoxic chemotherapy has been the standard of care for patients with advanced urothelial carcinoma based on improved survival compared to placebo. However, objective response rates are at best 50% and median overall survival is relatively poor at less than 18 months. This has driven the rationale for additional approaches. In first-line (1L) therapy for patients who are not cisplatin-eligible and as maintenance or second-line therapy (2L) for patients receiving first-line chemotherapy, immune checkpoint therapy has become the standard of care. However, treatment for patients who have previously received programmed death 1/ligand 1 inhibitor (PD-1/L1i) therapy.