ORLANDO, FL, USA (UroToday.com) - In 2014, there were 233 000 new cases of prostate cancer, with patients being of a median age of 66-years-old. It is estimated that by 2024, the number of prostate cancer survivors will extend from 2.9 million to 4.1 million men, which will make up almost 50% of all cancer survivors. These statistics underscore the importance of discovering the most efficacious, rational therapies that provide the best quality of life over the long term.
Dr. Mary Ellen Taplin discussed new treatments, biomarkers, and guidelines that defined the care of prostate cancer patients in 2014. She began with the ChemoHormonal Therapy versus Androgen Ablation Randomized Trial for Extensive Disease (CHAARTED) trial. This study stratified patients by extent of metastases (high vs low), age (< 70 vs > 70yo), ECOG PS (0-1 vs 2), Skeletal related events prevention (yes vs no) and prior ADT (< 12 vs > 12 months), and then randomized them to receiving ADT + docetaxel or ADT alone. Patients were followed for time to progression (at which point chemotherapy could be given at the investigator’s discretion) and overall survival. Seven hundred ninety men were accrued over 6.5 years, and analysis demonstrated 136 deaths in the ADT group vs 101 deaths in the chemotherapy group. OS was greater in the chemotherapy group at 57.6 months, vs 44 months in the ADT alone group (HR =0.61, CI 0.47-0.80, p=0.003). Among patients with high-volume disease, there was a 17-month improvement in median OS from 32 to 49 months in the chemotherapy group (HR=0.60, CI 0.45-0.81, p=0.0006). Dr. Taplin concluded that CHAARTED data has changed the standard of care for men with hormone sensitive high volume metastatic disease.
Next, she discussed the COU-AA-302 trial, which evaluated chemo-naïve mCRPC patients and randomized them to receive abiraterone + prednisone or placebo + prednisone, and followed them for radiographic progression-free survival (rPFS) and OS. Median rPFS was 16.5 months in the abiraterone group vs 8.3 months in the placebo arm (HR 0.53, CI 0.45-0.62, p < 0.001). Median OS was not reached for abiraterone vs 27.2 months for placebo (HR 0.75, CI 0.61-0.93, p=0.01).
The PREVAIL trial was a phase 3 trial that enrolled 1 700 chemo-naïve men with progressive mCRPC and randomized them to enzalutamide vs placebo, and evaluated for OS and rPFS. The enzalutamide group had significantly greater rPFS (13.8 vs 3.9 mo, HR 0.186, p < 0.0001), time to chemotherapy (28 vs 10.8 mo, HR 0.35, p < 0.0001), and OS (32.4 vs 30.2 mo, HR 0.7, p < 0.0001). The most common adverse effect experienced in the treatment arm was fatigue. Dr. Taplin concluded that enzalutamide is safe and effective, but we still need to determine the optimal sequencing of secondary AR approaches, combination approaches, biomarkers of response, and efficacy in earlier disease settings.
Next, Dr. Taplin touched on a number of negative phase 3 trials in prostate cancer, including investigations of orteronel, cabozantinib, ipilimumab, custirsen, dasatinib, and sunitinib. Points that can be gleaned from these trials include focusing more time on thorough investigation of drug dose and schedule, identifying whether the drug is hitting the intended target, exploring ethnic or national differences among patients, and identifying better biomarkers of response.
Dr. Taplin then segued to biomarkers that have proven to be useful. The most potentially impactful biomarker was AR-V7, an altered form of the androgen receptor that lacks a ligand-binding domain. Dr. Antonarakis from Johns Hopkins and his co-investigators interrogated AR-V7 status in CTCs, and assessed the association with survival outcomes. AR-V7 + patients on Enza/Abi had a significantly lower rPFS vs AR-V7 - patients (HR 12.7, CI 5.1-31.9, p < 0.001). Similarly, OS was lower in the AR-V7+ group (HR 5.5, CI 2.5-12, p < 0.001). Future study should be focused on finding the optimal assay to measure AR-V7, investigating the reproducibility of the original work, and validation of it as a biomarker in multi-institutional trials.
Dr. Taplin concluded her session with a review of relevant guidelines for prostate cancer in 2014, including the use of systemic therapy in men with mCRPC, prevention and management of chemotherapy-induced peripheral neuropathy in survivors, and the screening, assessment and care of anxiety and depressive symptoms in survivors.
Presented by Mary Ellen Taplin, MD at the 2015 Genitourinary Cancers Symposium - "Integrating Biology Into Patient-Centric Care" - February 26 - 28, 2015 - Rosen Shingle Creek - Orlando, Florida USA
Dana Farber Cancer Institute, Boston, MA USA
Reported by Nikhil Waingankar, MD, medical writer for UroToday.com