The study design is shown below. Patients with newly diagnosed mHSPC were enrolled on study between 2013 and 2017. The primary endpoint was overall survival. Patient enrollment was stratified and balanced by performance status, disease volume, and early administration of ADT (before or after registration). It was assumed that the median overall survival to the control arm would be 54 months based on prior studies at the time. The study would read out as positive if the median overall survival improved by 33% to 72 months. The study had 90% power with a one-sided alpha of 0.025 to detect this difference.
Baseline clinical characteristics were well balanced between treatment arms.
The median follow-up at the time of clinical data cutoff was 4.9 years. At this time, 30% of patients remained on therapy in the TAK-700 arm and 15.6% of patients remained on therapy in the bicalutamide arm. Overall survival in the control arm at the time of data cut-off was 70.2 months, compared to 81.1 months in the TAK-700 arm. This reflected a hazard ratio for death with TAK-700 of 0.86 (95% CI 0.72-1.02, p = 0.04).
Subgroup analysis is shown below.
Regarding secondary endpoints, TAK-700 improved progression-free survival from 23 months to 47.6 months (HR 0.58, p < 0.001) and resulted in a higher PSA complete response rate of 58%.
TAK-700 therapy was associated with higher rates of hypertension, including grade 3+ events, as well as fatigue, though there was no difference between treatment arms with regards to hot flashes. With regards to post-trial subsequent life-prolonging therapy, more patients in the control arm went on to receive life-prolonging therapy (77.4%) as compared to the TAK-700 arm (61.3%).
Dr. Agarwal then compared this study with other phase 3 trials leading to drug approvals in mHSPC. The table shown below is remarkable for the longer overall survival in the control arm, perhaps partially reflective of relatively lower rates of extensive disease patients, though the rate of this was also comparable to STAMPEDE.
Dr. Agarwal concluded his talk with several points. He noted that TAK-700 significantly improved progression-free survival and PSA responses relative to bicalutamide when combined with testosterone suppression in mHSPC. There was an approximately 11-month improvement in median overall survival that did not meet the pre-defined statistical significance cut-off for the trial. He also noted that enrollment in the study was broad, including 10% black patients and patients from many academic centers across the United States. The median overall survival in the control arm of 70 months is the highest rate reported in the literature and provides important information for survival estimates moving forward.
Presented by: Neeraj Agarwal, MD, Professor in the Division of Oncology, Department of Medicine, at the Huntsman Cancer Institute (HCI) at the University of Utah School of Medicine, Salt Lake City, Utah
Written by: Alok Tewari, MD, PhD, Medical Oncologist at the Dana-Farber Cancer Institute, at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Virtual Annual Meeting #ASCO21, June, 4-8, 2021