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Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer (TITAN)

Curated by Clinicians: Educational Forum with Videos, Abstracts and Conference Information
Videos
Conference Coverage
Conference Highlights Written by Physician Scientists
Presented by Soumyajit Roy, MBBS, MSc
Dr. Soumyajit Roy presented the results of an individual patient data meta-analysis of early PSA nadir in the ARASENS, LATITUDE, and TITAN trials.
Presented by Benjamin L. Maughan, MD, PharmD
Dr. Benjamin Maughan presented a retrospective observational cohort study using ConcertAI to assess rapid and deep prostate-specific antigen (PSA) response to apalutamide plus ADT and survival in mCSPC in real-world practice in the US (OASIS Project).
Presented by Benjamin H. Lowentritt, MD, FACS
Dr. Benjamin Lowentritt discussed a real-world comparison of PSA response in patients with mCSPC treated with apalutamide or enzalutamide. Deep PSA response, evaluated as ≥90% PSA decline (PSA90), is an important outcome after androgen receptor synthesis inhibitor initiation.
Presented by Neeraj Agarwal, MD
The 2024 ASCO GU symposium was host to a prostate cancer poster session. Neeraj Agarwal, MD, presented the results of a statistical extrapolation analysis of the TITAN study estimating median overall survival of metastatic hormone-sensitive prostate cancer (mHSPC)
Presented by Marc-Oliver Grimm, MD
Marc-Oliver Grimm, MD, discusses the final results of TITAN-TCC in metastatic urothelial carcinoma. Nivolumab is approved in second line metastatic urothelial carcinoma after platinum-based chemotherapy.
Presented by Axel S. Merseburger, MD, PhD
Dr. Axel Merseburger presented the results of a secondary analysis of TITAN that evaluated the effect of rapid ultra-low PSA decline in patients with metastatic castration-sensitive prostate cancer (mCSPC) who received apalutamide + ADT.
Presented by Neeraj Agarwal, MD, FASCO
Dr. Neeraj Agarwal discussed genomic aberrations associated with overall survival in mCSPC treated with apalutamide or placebo + ADT in the TITAN trial.1 In this exploratory analysis, Dr. Agarwal and colleagues reported the relationships between biomarkers and OS in TITAN.
Presented by Anders Bjartell MD, PhD FEBU
A number of androgen receptor targeting agents have been assessed, beginning with abiraterone acetate. In TITAN, the addition of apalutamide to ADT has demonstrated improvement in long-term outcomes for patients with mCSPC.
Presented by Simon Chowdhury, MD, PhD
At the metastatic prostate cancer session at the European Association of Urology 2021 Virtual Meeting, Dr. Simon Chowdhury presented results of outcomes in high and low-volume disease from the TITAN study.
Presented by Neeraj Agarwal, MD, FASCO
TITAN was the pivotal phase III trial demonstrating the benefit of apalutamide in mCSPC. After the publication of the primary results, the study was unblinded and patients who had not progressed on placebo could cross-over to apalutamide. Dr. Agarwal presented HRQoL data from this final analysis, after cross-over.
Presented by Simon Chowdhury, MD

The TITAN study demonstrated that the rates of both radiographic progression-free survival and overall survival were significantly improved in patients treated with apalutamide plus ADT versus those treated with placebo plus ADT.

Presented by Felix Y. Feng, MD
Dr. Felix Feng presented results of a post-hoc exploratory analysis of whether the Decipher Genomic Classifier (GC) score, and AR activity score, or an expression score for basal/luminal phenotype were associated with outcome for patients on the TITAN study.
Presented by Neeraj Agarwal, MD, FASCO
TITAN was a double-blind, placebo-controlled, phase III study which evaluated apalutamide 240 mg/day for patients with mCSPC. This oral presentation updates the original dataset and provides time to second progression by the different second-line therapies.

 

Presented by Dana Rathkopf, MD
Dr. Dana Rathkopf discussed two oral presentations: 1) Time to second progression (PFS2) in patients from TITAN with mCSPC 2) Luminal B subtype as a predictive biomarker of docetaxel benefit for newly diagnosed mHSPC: A correlative study of E3805 CHAARTED.
Presented by Mustafa Ozguroglu, MD
The phase III TITAN study showed that apalutamide plus ADT improves rPFS and OS in a broad group of patients with mCSPC. Dr. Mustafa Ozguroglu and colleagues presented results of their hoc analysis evaluating apalutamide plus ADT based on baseline prognostic risk as defined in LATITUDE study.
Presented by Neeraj Agarwal, MD, FASCO
Apalutamide has been shown to enhance overall survival (OS) and radiographic progression-free survival (rPFS).  This study led to the FDA approval of apalutamide for mCSPC. Dr. Neeraj Agarwal presented data on the first subsequent therapy after progression on apalutamide.
Presented by Neeraj Agarwal, MD, FASCO
Dr. Agarwal presented on the time to secondary progression in patients on TITAN. The TITAN trial is a phase III randomized double blind study, which evaluated the effect of apalutamide in patients with metastatic castrate sensitive prostate cancer receiving androgen deprivation therapy. 
Presented by Neeraj Agarwal, MD, FASCO
In the TITAN study, compared with placebo, the addition of apalutamide to ADT significantly improved radiographic progression-free survival and overall survival in patients with mCSPC. Dr. Agarwal and colleagues evaluated pain, fatigue, and overall health-related quality of life of patients in TITAN.
Presented by Michael A. Carducci, MD
Dr. Michael Carducci presented three prostate cancer studies: TITAN (apalutamide versus placebo in mCSPC), EORTC 1333/PEACE III (enzalutamide and Ra223 safety analysis), and Alliance A031201 (enzalutamide combination therapy in mCRPC).
Presented by Kim N. Chi, MD, FRCPC
The TITAN study was a phase III, double-blind, randomized study designed to determine whether apalutamide plus ADT improves radiographic progression-free survival (rPFS) and overall survival (OS) compared with placebo plus ADT in men with mCSPC.
Presented by Kim N. Chi, MD, FRCPC
Apalutamide is a potent androgen receptor antagonist (AR), similar to enzalutamide, and prevents AR nuclear translocation and transcription of AR gene targets. In this presentation, Dr. Kim Chi presented data from the TITAN study involving use of apalutamide for patients with mHSPC.
Physician-Scientist Review Articles
State of the Evidence Review Articles
January 20, 2020
New treatment approaches are needed for patients with advanced prostate cancer to extend survival without compromising health-related quality of life (HRQoL). Patient-reported outcomes (PROs) provide meaningful data about disease symptoms, treatment tolerability, and overall HRQoL. PROs are important to both clinicians and patients making treatment choices. They also have increasing importance to regulatory agencies when approving drug therapies,1 including pharmaceutical labeling claims, as well as product reimbursement, and health care policy.
Publications
Peer-Reviewed Journal Abstracts

Patients with limited-stage primary testicular lymphoma (PTL) typically receive a multimodal regimen, including 6 cycles of R-CHOP, despite limited evidence. In low-risk diffuse large B-cell lymphoma, de-escalation to 4 R-CHOP cycles has proven non-inferior.

Investigation remains incomplete regarding potential variations in the effect of androgen receptor pathway inhibitors, including apalutamide, based on baseline tumor burden in patients with metastatic castration-sensitive prostate cancer (mCSPC).

In the TITAN trial of patients with metastatic castration-sensitive prostate cancer (mCSPC), deep and rapid prostate-specific antigen (PSA) decline with apalutamide plus androgen deprivation therapy (ADT) was associated with longer overall survival (OS), radiographic progression-free survival (rPFS), time to PSA progression (TTPP), and time to castration resistance (TTCR) compared with no decline (all p < 0.

Purpose: Early PSA response has been found to be prognostic of outcomes in metastatic hormone sensitive prostate cancer. We performed a secondary analysis of the TITAN trial to determine if early PSA response was predictive of treatment efficacy in metastatic hormone sensitive prostate cancer patients.

In prostate cancer treated with androgen deprivation therapy (ADT), the initial sign of treatment resistance is often prostate-specific antigen (PSA) progression, followed by radiographic progression.

This summary describes the results from an additional (or post hoc) analysis of the TITAN study. The TITAN study looked at whether the prostate cancer treatment apalutamide could be used to treat individuals with metastatic castration-sensitive prostate cancer (or mCSPC).

The first interim analysis of the phase III, randomized, double-blind, placebo-controlled, multinational TITAN study demonstrated improved overall survival (OS) and radiographic progression-free survival (rPFS) with apalutamide added to ongoing androgen deprivation therapy (ADT) in patients with metastatic castration-sensitive prostate cancer (mCSPC).

Apalutamide plus androgen-deprivation therapy (ADT) has been approved for treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC) based on data from phase 3 TITAN study. This analysis was conducted to describe pharmacokinetics of apalutamide and N-desmethyl-apalutamide and explore relationships between apalutamide exposure and selected clinical efficacy and safety observations.

Exploratory analysis of prostate cancer-related pain and fatigue on health-related quality of life in patients with metastatic castration-sensitive prostate cancer (mCSPC) receiving apalutamide (240 mg/day) or placebo, with continuous androgen-deprivation therapy (ADT), in the phase 3, randomized, double-blind placebo-controlled TITAN trial (NCT02489318).

The first interim analysis of the phase III, randomized, placebo-controlled TITAN study showed that apalutamide significantly improved overall survival (OS) and radiographic progression-free survival in patients with metastatic castration-sensitive prostate cancer (mCSPC) receiving ongoing androgen deprivation therapy (ADT).

To evaluate the efficacy and safety of apalutamide + androgen deprivation therapy versus androgen deprivation therapy alone in Japanese patients with metastatic castration-sensitive prostate cancer from the phase 3, randomized, global TITAN study.

Background: In the phase 3 TITAN study, the addition of apalutamide to androgen deprivation therapy (ADT) significantly improved the primary endpoints of overall survival and radiographic progression-free survival in patients with metastatic castration-sensitive prostate cancer. We aimed to assess health-related quality of life (HRQOL) in TITAN, including pain and fatigue.

Apalutamide is an inhibitor of the ligand-binding domain of the androgen receptor. Whether the addition of apalutamide to androgen-deprivation therapy (ADT) would prolong radiographic progression-free survival and overall survival as compared with placebo plus ADT among patients with metastatic, castration-sensitive prostate cancer has not been determined.

Press Releases
Official Announcements on Clinical Developments
Addition of 240mg strength allows prescribers flexibility to prescribe one 240mg tablet or four 60mg tablets once-daily based on patient needs

Reno, Nevada (UroToday.com) -- The Janssen Pharmaceutical Companies of Johnson & Johnson announced the availability of an additional tablet strength of ERLEADA® (apalutamide) in the United States. The introduction of the 240mg tablet provides the first-and-only option for a once-daily, single-tablet Androgen Receptor Inhibitor (ARI) approved for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and for the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC).
San Francisco, CA (UroToday.com) -- The Janssen Pharmaceutical Companies of Johnson & Johnson announced that the U.S. Food and Drug Administration (FDA) has approved ERLEADA® (apalutamide) for the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC).1 This approval follows FDA Priority Review Designation of the supplemental New Drug Application (sNDA) that was submitted in April 2019 and reviewed through the FDA Real-Time Oncology Review program. The new indication for ERLEADA® will make this androgen receptor inhibitor available for the approximately 40,000 people in the U.S. diagnosed with mCSPC annually.2
San Francisco, CA (UroToday.com) -- Supplemental New Drug Application Supported by Phase 3 TITAN Study; Submitted Through FDA Real-Time Oncology Review Program

The Janssen Pharmaceutical Companies of Johnson & Johnson announced the submission of a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) seeking approval of a new indication for ERLEADA® (apalutamide) for the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC). The sNDA is based on findings from the Phase 3 TITAN study, whose dual primary endpoints, overall survival (OS) and radiographic progression-free survival (rPFS), were both achieved. These data will be presented at the upcoming American Society of Clinical Oncology (ASCO) Annual Meeting during an oral abstract session on Friday, May 31st.