Two large trials (LATITUDE and STAMPEDE), presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, showed that upfront treatment with abiraterone plus prednisone and androgen deprivation therapy (ADT) in hormone-sensitive metastatic prostate cancer improves overall survival compared to ADT alone. These results will likely led to immediate practice change.
- According to results from the randomized, placebo-controlled phase III LATITUDE trial, presented by Karim Fizazi, MD, PhD (Gustave Roussy, Vilejuif, France), at the plenary session (Abstract LBA3), the addition of abiraterone (1000 mg daily) and prednisone (5 mg daily) to ADT significantly increases overall survival (OS). After a median follow-up of 30.4 months, the median OS was not reached in patients who received abiraterone plus ADT (n = 597), compared with 34.7 months in patients (n = 602) receiving ADT plus placebo (HR 0.62, P<.001). Three-year OS rates were 66% and 49%, respectively. Similar improvements with abiraterone were seen in PFS (33.0 months vs 14.8 months; HR 0.47, P<.0001). Addition of abiraterone also significantly improved time to PSA progression, time to pain progression, and time to subsequent therapy. Grade 3 or higher adverse events (AEs) more commonly observed with abiraterone were hypertension (20%), hypokalemia (10.8%), liver enzyme increase (AST 3% and ALT 4.2%), and cardiac disorder (3.8%). In his discussion of this abstract, Eric Small, MD (University of California San Francisco, California, United States), called this trial a “profoundly positive study” and indicated that abiraterone should now be considered a new standard of care for patients with untreated high-risk metastatic prostate cancer (and potentially for all patients with untreated metastatic cancer). He pointed out that the benefit obtained from the addition of abiraterone to ADT appears to be similar to the benefit with docetaxel. He also highlighted that evaluation of quality of life and financial toxicity, as well as testing this therapy earlier at the time of increasing PSA and in combination with docetaxel, is warranted.
- Further support for the use of abiraterone in untreated hormone-sensitive prostate cancer was provided by results from the abiraterone comparison arm of the STAMPEDE trial (Abstract LBA5003), presented by Nicholas James, MBBS, PhD (University of Birmingham, United Kingdom), which demonstrated that addition of abiraterone to standard of care (SOC) resulted in a 37% improvement in OS (HR 0.63, P = .00000115). Results consistently favored abiraterone across all predefined subgroups, including both M0 and M1 disease. Abiraterone was also associated with a 71% improvement in time to treatment failure (HR 0.29, P = .337×10-61), and it reduced symptomatic skeletal events by 55%. Among grade 3-5 AEs that were more common with the abiraterone arm than with SOC were the expected cardiovascular events (10% vs 4%), including hypertension and dysrhythmia, and hepatic events (7% vs 1%), mainly transaminase elevations. Tanya Dorff, MD (University of Southern California, Los Angeles, California, United States), the discussant of this abstract, highlighted that we now have two very valid choices for upfront intensification and that there is a ‘’striking benefit’’ from upfront abiraterone in patients with metastatic prostate cancer.