(UroToday.com) The 2024 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA between January 25th and 27th was host to a prostate cancer poster session. Dr. Neeraj Agarwal presented the results of a statistical extrapolation analysis of the TITAN study estimating median overall survival of metastatic hormone sensitive prostate cancer (mHSPC) patients treated with apalutamide versus placebo.
TITAN is a double-blind, phase 3 randomized trial that randomized patients with mHSPC to androgen deprivation therapy (ADT) plus apalutamide (240 mg/day) or placebo. Notably, prior docetaxel usage was permitted (1.2% of study cohort). 81% of patients presented with de novo mHSPC and 63% of patients had CHAARTED high volume disease. The first reported outcomes of this trial demonstrated a significant overall survival (OS) benefit for ADT + apalutamide (HR: 0.67, 95% CI: 0.51 to 0.89),1 and with longer follow-up (median follow-up of 44 months) the OS benefit with the addition of apalutamide (HR: 0.65, 95% CI: 0.53 to 0.79) had been maintained, despite 39.5% of patients in the placebo arm crossing over to the treatment arm.2
However, at the time of final analysis, the median OS was not reached in either the apalutamide arm or the subgroups after the median follow up of 44 months. As such, Dr. Agarwal’s team aimed to estimate the OS medians for the apalutamide and placebo arms beyond the reported TITAN follow-up, by fitting validated survival models.
OS was predicted for the overall population treated with apalutamide or placebo, with and without Inverse probability of censoring weighting (IPCW) crossover adjustment, and for the low and high-volume, including high-volume synchronous and metachronous subgroups.
General population mortality-adjusted TITAN patient-level data was fitted to six parametric models (Weibull, exponential, log-normal, log-logistic, generalized gamma, and Gompertz) using the individual fits approach. The best fit was determined by statistical and visual fits, along with the Akaike Information Criterion (AIC)/Bayesian Information Criterion (BIC) ranking, according to the recommendations of the National Institute for Health and Care Excellence Decision Support Unit 14.
Using the best fit extrapolation approach, the estimated median overall survival for the overall apalutamide-treated mHPSC population was 71.8 months, which correlated to an estimated median improvement of up to 32 months versus placebo. The median OS values predicted by the other five models ranged between 62.4 and 78.1 months.
Across subgroups, best fit models estimated a median OS of 113.7 months for apalutamide in low-volume disease patients and a consistent median OS of 52 months for high-volume disease subgroups.
Dr. Agarwal concluded that while the results of this extrapolation study should not be equated to those of a clinical trial, this analysis meets an evidence gap by predicting median OS in the apalutamide arm of the TITAN study for the overall mHSPC population, as well as for various subgroups of this heterogeneous population. These findings strengthen the evidence supporting early treatment with apalutamide across the broad mHSPC population.
Presented by: Neeraj Agarwal, MD, Professor, Department of Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2024 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, San Francisco, CA, January 25th – January 27th, 2024
References:1. Chi KN, Agarwal N, Bjartell A, et al. Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med. 2019;381(1):13-24.
Related Content: Apalutamide Confirms Overall Survival Benefit at 44-Months in Metastatic Castration-Sensitive Prostate Cancer - The TITAN Study - Neeraj Agarwal