TALAPRO-2: A two-part, placebo-controlled phase III study of talazoparib (TALA) with enzalutamide (ENZA) in metastatic castration-resistant prostate cancer (mCRPC).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. TPS337-TPS337 ◽  
Author(s):  
Neeraj Agarwal ◽  
Neal D. Shore ◽  
Curtis Dunshee ◽  
Lawrence Ivan Karsh ◽  
Beth Sullivan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Primary Endpoint ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Prior Treatment ◽  
Secondary Endpoint ◽  
Phase Iii ◽  
Parp Inhibition ◽  
Rank Test ◽  
Double Blind Study

TPS337 Background: ENZA is approved to treat men with CRPC. TALA is a poly(ADP-ribose) polymerase (PARP) inhibitor that inhibits PARP1/PARP2 and traps PARP on DNA, preventing DNA damage repair (DDR), and causing cell death in BRCA1/2-mutated cells. TALA is approved in the US to treat germline BRCA1/2-mutated HER2- locally advanced/metastatic breast cancer. A combination of TALA with ENZA in mCRPC may improve clinical outcomes. Methods: Eligible patients (pts) in parts (P) 1 and 2 of this study are aged ≥18 years; have asymptomatic/mildly symptomatic mCRPC, ECOG PS ≤1, and no brain metastases; and have not received taxanes/novel hormonal therapy (NHT). P1 is an open label study to confirm the starting dose of TALA to be given in combination with ENZA. P2 is a randomized double-blind study that will evaluate the safety, efficacy and pt reported outcomes of TALA (0.5 mg QD) + ENZA (160 mg QD) vs placebo + ENZA in 2 cohorts (C). C1: pts with mCRPC (all comers) (N = 560); C2: pts with DDR gene mutations likely to sensitize to PARP inhibition (DDR deficient) (N = 300). Randomization will be stratified by prior treatment with NHT for castration sensitive prostate cancer (CSPC) or prior treatment with taxane-based chemotherapy for CSPC (yes/no), and DDR mutation status (deficient vs. nondeficient/unknown). For P1, the primary endpoint is safety; the secondary endpoint is pharmacokinetics of TALA and ENZA. For P2, the primary endpoint is radiographic progression-free survival (rPFS), defined as time to progression in soft tissue per RECIST v1.1 or in bone per PCWG3 criteria or death and evaluated separately in all comers (C1) and DDR-deficient (DDR-deficient pts from C1 and C2 combined, N = 380 pts) populations. The key secondary endpoint is overall survival. Efficacy will be assessed by radiography every 8 weeks up to week 25 and every 8-12 weeks thereafter. P2 analysis for rPFS is powered at 90% and 85% using a 2-sided log-rank test with alpha of 0.025, respectively, in the all comers and DDR deficient populations. This study was sponsored by Pfizer Inc. Clinical trial information: NCT03395197.

TALAPRO-2: Part 2 (P2) of the placebo-controlled phase 3 study of talazoparib (TALA) with enzalutamide (ENZA) in metastatic castration-resistant prostate cancer (mCRPC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS5092-TPS5092
Author(s):  
Neeraj Agarwal ◽  
Neal D. Shore ◽  
Curtis Dunshee ◽  
Lawrence Ivan Karsh ◽  
Beth Sullivan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Group Performance ◽  
Parp Inhibitor ◽  
Performance Status ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Metastatic Breast ◽  
Prior Treatment ◽  
Rank Test ◽  
Double Blind Study

TPS5092 Background: ENZA is approved to treat men with CRPC. TALA is a poly(ADP-ribose) polymerase (PARP) inhibitor that inhibits PARP1/PARP2 and traps PARP on DNA, preventing DNA damage repair (DDR), and causing cell death in BRCA1/2-mutated cells. TALA is approved in the US to treat germline BRCA1/2-mutated HER2- locally advanced/metastatic breast cancer. A combination of TALA with ENZA in mCRPC may improve clinical outcomes. TALAPRO-2 (NCT03395197) is a 2-part study to evaluate the efficacy, safety, pharmacokinetics and (patient) pt-reported outcomes of the combination treatment. The focus here is on P2 of TALAPRO-2. Methods: Approximately 860 pts are planned to be enrolled in P2 from multinational sites. Pts are aged ≥18 years, have asymptomatic/mildly symptomatic mCRPC, Eastern Cooperative Oncology Group performance status ≤1, no brain metastases, and have not received taxanes/novel hormonal therapy (NHT). P2 is a randomized double-blind study that will evaluate safety, efficacy, and pt-reported outcomes of TALA (0.5 mg QD) + ENZA (160 mg QD) vs placebo + ENZA (160 mg QD). Pts will be randomized to 1 of 2 treatment groups: TALA + ENZA, or matching placebo + ENZA. Randomization will be stratified by prior treatment with NHT for castration-sensitive prostate cancer (CSPC) or prior treatment with taxane-based chemotherapy for CSPC (yes/no) and DDR mutation status (deficient vs. nondeficient/unknown). The primary endpoint is radiographic progression-free survival (rPFS), defined as time to progression in soft tissue per RECIST v1.1 or in bone per PCWG3 criteria or death. The key secondary endpoint is overall survival (OS). Efficacy will be assessed by radiography every 8 weeks up to week 25 and every 8-12 weeks thereafter. The analyses of rPFS will be compared between TALA in combination with ENZA and placebo in combination with ENZA by using a 1-sided stratified log-rank test. OS will be evaluated separately in the all comers and the DDR-deficient populations. Pt recruitment is ongoing. Results: n/a. Conclusions: n/a. Clinical trial information: NCT03395197.

Gemcitabine plus docetaxel versus docetaxel in patients (pts) with HER2-negative locally advanced or metastatic breast cancer (MBC): A randomized phase III study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1015-1015
Author(s):  
D. L. Nielsen ◽  
S. T. Langkjer ◽  
K. Bjerre ◽  
S. Cold ◽  
L. Stenbygaard ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Agent ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Rank Test ◽  
Hematologic Toxicity ◽  
Phase Iii Study ◽  
Her 2 ◽  
Grade 3

1015 Background: Gemcitabine (G), either as a single agent or in combination with taxanes, has demonstrated efficacy in MBC in phase II and III studies. We conducted a phase III study to compare time to progression (TTP) of G plus docetaxel (T) versus (vs.) T alone. The secondary endpoints included overall survival (OS), overall response rate (ORR), and toxicity. Methods: Females with HER-2-negative locally advanced or MBC and a WHO performance status ≤ 2 were randomized to GT (G 1,000mg/m2 day 1 + 8; T 75mg/m2 day 1) or T (100mg/m2 day 1) every 21 days. Pts were previously untreated, had prior anthracycline-based (neo)adjuvant chemotherapy or had received a single prior anthracycline-bsed chemotherapy regimen for MBC. Time-to-event endpoints were estimated using the Kaplan-Meier method, and the log-rank test was applied for comparisons between regimens. The planned sample size was 254 evaluable pts with α I and β of 0.05 and 0.90, respectively. Results: A total of 336 pts were randomized (170 GT; 166 T), data from one centre are yet missing and the present evaluation is based on data from 306 pts (155 GT; 151 T). The pts had a median age of 58 years in both regimens; range 36–73 years and 30–74 years, respectively. The median TTP was 7.5 months for the GT regimen vs. 6.5 months for the T regimen. The GT arm demonstrated an ORR of 44% vs. 38% in the T arm with 4 and 3 % complete responses, respectively. The OS was 13.4 vs. 13.2 months in the GT and T arm, respectively. Hematologic toxicity was common, especially grade 3–4 neutropenia (GT = 69%; T = 61%); infection was reported in 22 and 20% of the pts, respectively (none of the pts received G-CSF). The most commonly reported non-hematologic toxicities of grade 3–4 included mucositis (GT = 2%; T = 5%), diarrhea (GT = 4%; T = 7 %), fatigue (GT = 6%; T = 11%), oedema (GT = 10%; T = 3%), and peripheral neuropathy (GT = 9%; T = 28%). Conclusions: Preliminary data of GT as first- or second-line chemotherapy demonstrates a TTP advantage among HER-2-negative pts with advanced breast cancer. Updated results and proper statistical analyses will be presented. No significant financial relationships to disclose.

Alliance A031201: A phase III trial of enzalutamide (ENZ) versus enzalutamide, abiraterone, and prednisone (ENZ/AAP) for metastatic castration resistant prostate cancer (mCRPC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5008-5008 ◽  
Author(s):  
Michael J. Morris ◽  
Glenn Heller ◽  
Alan Haruo Bryce ◽  
Andrew J. Armstrong ◽  
Himisha Beltran ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Progression Free Survival ◽  
Prior Treatment ◽  
Phase Iii ◽  
Rank Test ◽  
Circulating Microrna ◽  
Type I ◽  
Castration Resistant Prostate Cancer ◽  
Primary Analysis ◽  
Log Rank Test

5008 Background: Androgen receptor (AR) signaling is an important growth mechanism in mCRPC, providing the rationale for treatment with AR axis inhibitors such as ENZ and AAP. Targeting AR with anti-androgens such as ENZ can result in compensatory autocrine and paracrine androgenic stimulation. Therefore, using ENZ with the androgen biosynthesis inhibitor AAP to dampen these resistance mechanisms could improve clinical outcomes relative to ENZ alone. Methods: Men with progressive mCRPC by Prostate Cancer Working Group 2 criteria were eligible. Prior treatment with taxanes for mCRPC and any prior treatment with ENZ or AAP was exclusionary. Patients (pts) were randomized 1:1 to ENZ or ENZ/AAP at standard FDA-approved doses. Randomization was stratified by prior chemotherapy and Halabi prognostic three risk groups. Castrating therapy was maintained. The primary endpoint was overall survival (OS) defined as the date of randomization from date of death or last follow-up. The log-rank test had 90% power to detect a hazard ratio for OS of 0.77 with a one-sided type I error rate of 0.025. Secondary endpoints included radiographic progression free survival (rPFS) and on-treatment PSA declines. Exploratory endpoints included imaging changes, and changes in serum biomarkers such as androgens, angiokines, and circulating microRNA and RNA. The primary analysis was based on the stratified log-rank test adjusting on the stratification factors. Results: Between January 2014 and August 2016, 1311 men were randomized: 657 to ENZ and 654 to ENZ/AAP. Groups were well balanced between arms, including stratification variables. 15.6% of pts were high risk, 35.3% intermediate, and 48.1% low. Median OS was 33.6 mo (95% CI 30.5-36.4) and 32.7 mo (29.9-35.4) respectively, two-sided p = 0.53. Fifty percent PSA decline rate was 80% vs. 76.5%. Grade 3-5 adverse events (AE) (all attributions) were 55.6% and 68.8% respectively. Treatment discontinuation due to AEs occurred in 5% and 12%, pt withdrawal in 5% and 13%, and progression or death in 57% and 48% of pts respectively. Conclusions: Addition of abiraterone acetate to enzalutamide did not prolong survival in men with mCRPC. The combination resulted in more AEs than enzalutamide alone. Support: U10CA180821, U10CA180882, U24CA196171; https://acknowledgments.alliancefound.org . Clinical trial information: NCT01949337.

Phase III open-label, randomized, multicenter study of NKTR-102 versus treatment of physician's choice (TPC) in patients (pts) with locally recurrent or metastatic breast cancer (MBC) previously treated with an anthracycline, a taxane, and capecitabine (ATC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS1140-TPS1140
Author(s):  
Edith A. Perez ◽  
Ahmad Awada ◽  
Joyce O'Shaughnessy ◽  
Hope S. Rugo ◽  
Christopher Twelves ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Topoisomerase I ◽  
Single Agent ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Rank Test ◽  
Continuous Exposure ◽  
Open Label ◽  
Metastatic Setting

TPS1140^ Background: NKTR-102 is a topoisomerase I inhibitor-polymer conjugate that hydrolyzes to provide continuous exposure to SN-38. A phase 2 trial of single-agent NKTR-102 was conducted in pts with 3rd-line MBC; 2 schedules (q14d; q21d) investigated a dose of 145 mg/m2. ORR was 29% (including 3% CR) with the prior ATC subset demonstrating an ORR of 31%. Dosing q21d was better tolerated; in this arm, median PFS and OS equaled 5.3m and 13.1m, respectively. Trial Design: Pts will be randomized 1:1 to receive single-agent NKTR-102 or TPC in an open-label, randomized, multicenter phase 3 study in pts with advanced breast cancer. Key Entry Criteria: Adult females, with ECOG 0 or 1 with adequate liver, kidney and marrow function. All pts must have received prior therapy with ATC (these drugs can be administered in the neo/adjuvant or locally advanced/metastatic setting). Prior A is not mandated if contraindicated. Prior toxicities must have resolved to ≤ Grade 1 (except sensory neuropathy ≤ Grade 2; complete resolution of prior diarrhea). Pts with brain metastases may be eligible, if lesions are stable for prior 3 weeks without steroids. Methods: Primary efficacy endpoint is OS. Secondary endpoints include: ORR by RECIST v1.1, clinical benefit rate (ORR+SD > 6 months), PFS and QoL. NKTR-102 is given IV at 145 mg/m2 over 90-min every 21 days without premedications. Pts randomized to TPC receive 1 of the following: eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel or nab-paclitaxel (the agent must be available at the treating institution). Pts are stratified by region, prior eribulin and receptor status (TNBC, Her2+ or Other). Target Accrual: ~840 pts will be required for sufficient events to occur in the planned follow-up time; OS will be compared using a two-sided log-rank test; 1 interim analysis will occur when 50% of the deaths are reported. PK sampling is performed in a subset of pts. CTCs (isolated by Apocell ApoStream technology) are serially assessed for potential predictive markers of response and toxicity. Enrollment is expected to remain open until late 2013.

Updated results of European Organization for Research and Treatment of Cancer (EORTC) phase 2 trial 1202 cabazitaxel in patients with metastatic or inoperable locally advanced dedifferentiated liposarcoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11518-11518
Author(s):  
Roberta Sanfilippo ◽  
Richard L Hayward ◽  
Jammbe Musoro ◽  
Charlotte Benson ◽  
Michael Gordon Leahy ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Objective Response ◽  
Locally Advanced ◽  
Phase Iii ◽  
Dedifferentiated Liposarcoma ◽  
Study Endpoint ◽  
Primary Study ◽  
Primary Analysis ◽  
European Organization ◽  
Experimental Drugs

11518 Background: Treatment options for patients with unresectable and/or metastatic dedifferentiated liposarcoma (DDLPS) are limited. The most effective agents include doxorubicin, ifosfamide, trabectedin and eribulin, but, in general, objective response rates (ORR) and progression free survival (PFS) are modest. Cabazitaxel exerts its effect through inhibition of microtubular disassembly and has been shown to be relatively safe, effective and well-tolerated. EORTC 1202 assessed whether cabazitaxel demonstrated sufficient antitumor activity in patients with metastatic or inoperable locally advanced DD LPS to justify further investigation in a phase III setting. Methods: This was an international multi-center, open label single arm phase II trial. The clinical cut-off date for the primary analysis was performed on August 31, 2020. Data base lock was performed on February 2, 2021. Eligible patients with metastatic or inoperable locally advanced DD LPS, after a centralized pathological review, were treated with cabazitaxel 25mg/m² IV infusion over 1 hour every 21 days. Primary endpoint was PFS rate at 12 weeks assessed by local investigator per RECIST 1.1. Based on a Simon two-stage design, at least 4 out of 17 (Stage 1) and 11 out of 37 (Stage 2) eligible and evaluable patients who are progression-free at 12 weeks were needed. Currently, a centralized radiological assessment is ongoing. Results: Forty patients were registered by 10 institutions in 4 countries between March 2015 and March 2019, with 2 patients being ineligible. One patient was still on treatment at the clinical cut-off date. The number of cycles ranged from 1 to 30, with a median of 5; 26 patients (65%) received at least 4 cycles of cabazitaxel. PFS at 12 weeks was 55% (conditional 1-sided 95% CI 40.8-100), achieving the primary study endpoint. The median FU was 21.6 months, median PFS was 6 months and median OS 21 months. RR was 8% with one CR and two PR. Twenty-three(60.5%) pts had a SD. Disease control (PR+SD) was achieved in 26 patients (68%). The most common cabazitaxel -related grade >3 adverse events in all 40 registered patients were Neutrophil count decreased (50%), febrile neutropenia (25%), fatigue (12.5%), and anemia (10%). There were no cabazitaxel-related deaths. Conclusions: EORTC 1202 met its primary endpoint, with 21/38 pts (55%) being progression-free at 12 weeks. Results of this trial confirm activity of cabazitaxel in patients with metastatic or inoperable locally advanced DD LPS and looks interesting if compared to the other available options and experimental drugs recently reported in this patient population. Clinical trial information: NCT01913652.

scholarly journals Simulation of an HDR “Boost” with Stereotactic Proton versus Photon Therapy in Prostate Cancer: A Dosimetric Feasibility Study

2020 ◽  
Author(s):  
Jill S. Remick ◽  
Pouya Sabouri ◽  
Mingyao Zhu ◽  
Søren M. Bentzen ◽  
Kai Sun ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dose Escalation ◽  
Locally Advanced ◽  
High Dose Rate ◽  
Rank Test ◽  
High Dose ◽  
Prostate Brachytherapy ◽  
High Risk Prostate Cancer ◽  
Prostate Size ◽  
Ct Simulation

Abstract Purpose/Objectives To compare the dose escalation potential of stereotactic body proton therapy (SBPT) versus stereotactic body photon therapy (SBXT) using high-dose rate prostate brachytherapy (HDR-B) dose-prescription metrics. Patients and Methods Twenty-five patients previously treated with radiation for prostate cancer were identified and stratified by prostate size (≤ 50cc; n = 13, > 50cc; n = 12). Initial CT simulation scans were re-planned using SBXT and SBPT modalities using a prescription dose of 19Gy in 2 fractions. Target coverage goals were designed to mimic the dose distributions of HDR-B and maximized to the upper limit constraint for the rectum and urethra. Dosimetric parameters between SBPT and SBXT were compared using the signed-rank test and again after stratification for prostate size (≤ 50cm3 and >50cm3) using the Wilcoxon rank test. Results Prostate volume receiving 100% of the dose (V100) was significantly greater for SBXT (99%) versus SBPT (96%) (P ≤ 0.01), whereas the median V125 (82% vs. 73%, P < 0.01) and V200 (12% vs. 2%, P < 0.01) was significantly greater for SBPT compared to SBXT. Median V150 was 49% for both cohorts (P = 0.92). V125 and V200 were significantly correlated with prostate size. For prostates > 50cm3, V200 was significantly greater with SBPT compared to SBXT (14.5% vs. 1%, P = 0.005), but not for prostates 50cm3 (9% vs 4%, P = 0.11). Median dose to 2cm3 of the bladder neck was significantly lower with SBPT versus SBXT (9.6 Gy vs. 14 Gy, P < 0.01). Conclusion SBPT and SBXT can be used to simulate an HDR-B boost for locally advanced prostate cancer. SBPT demonstrated greater dose escalation potential than SBXT. These results are relevant for future trial design, particularly in patients with high risk prostate cancer who are not amenable to brachytherapy.

Final results from ClarIDHy, a global, phase III, randomized, double-blind study of ivosidenib (IVO) versus placebo (PBO) in patients (pts) with previously treated cholangiocarcinoma (CCA) and an isocitrate dehydrogenase 1 (IDH1) mutation.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 266-266
Author(s):  
Andrew X. Zhu ◽  
Teresa Macarulla ◽  
Milind M. Javle ◽  
Robin Kate Kelley ◽  
Sam Joseph Lubner ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Primary Endpoint ◽  
Failure Time ◽  
Objective Response ◽  
Idh1 Mutation ◽  
High Rate ◽  
Phase Iii ◽  
Double Blind Study ◽  
Grade 3

266 Background: CCA is a rare cancer for which there are limited effective therapies. IDH1 mutations occur in ~20% of intrahepatic CCAs, resulting in production of the oncometabolite D-2-hydroxyglutarate, which promotes oncogenesis. IVO (AG-120) is a first-in-class, oral, small-molecule inhibitor of mutant IDH1 (m IDH1). ClarIDHy aimed to demonstrate the efficacy of IVO vs PBO in pts with unresectable or metastatic m IDH1 CCA. The primary endpoint was met with significant improvement in progression-free survival (PFS) by independent radiology center (IRC) with IVO vs PBO (hazard ratio [HR] = 0.37, p < 0.0001). Objective response rate (ORR) and stable disease for IVO were 2.4% (3 partial responses) and 50.8% (n = 63) vs 0% and 27.9% (n = 17) for PBO. IVO pts experienced significantly less decline in physical and emotional functioning domains of quality of life at cycle 2 day 1 vs PBO pts (nominal p < 0.05). Methods: Pts with m IDH1 CCA were randomized 2:1 to IVO (500 mg PO QD) or matched PBO and stratified by prior systemic therapies (1 or 2). Key eligibility: unresectable or metastatic m IDH1 CCA based on central testing; ECOG PS 0–1; measurable disease (RECIST v1.1). Crossover from PBO to IVO was permitted at radiographic progression. Primary endpoint: PFS by IRC. Secondary endpoints included overall survival (OS; by intent-to-treat), ORR, PFS (by investigator), safety, and quality of life. The planned crossover-adjusted OS was derived using the rank-preserving structural failure time (RPSFT) model. Results: As of 31 May 2020, ~780 pts were prescreened for an IDH1 mutation and 187 were randomized to IVO (n = 126) or PBO (n = 61); 13 remain on IVO. Median age 62 y; M/F 68/119; 91% intrahepatic CCA; 93% metastatic disease; 47% had 2 prior therapies. 70% of PBO pts crossed over to IVO. OS data were mature, with 79% OS events in IVO arm and 82% in PBO. Median OS (mOS) was 10.3 months for IVO and 7.5 months for PBO (HR = 0.79; 95% CI 0.56–1.12; one-sided p = 0.093). The RPSFT-adjusted mOS was 5.1 months for PBO (HR = 0.49; 95% CI 0.34–0.70; p < 0.0001). Common all-grade treatment emergent adverse events (TEAEs, ≥ 15%) in the IVO arm: nausea 41%, diarrhea 35%, fatigue 31%, cough 25%, abdominal pain 24%, decreased appetite 24%, ascites 23%, vomiting 23%, anemia 18%, and constipation 15%. Grade ≥ 3 TEAEs were reported in 50% of IVO pts vs 37% of PBO pts, with grade ≥ 3 treatment-related AEs in 7% of IVO pts vs 0% in PBO. 7% of IVO pts experienced an AE leading to treatment discontinuation vs 9% of PBO pts. There were no treatment-related deaths. Conclusions: IVO was well tolerated and resulted in a favorable OS trend vs PBO despite a high rate of crossover. These data – coupled with statistical improvement in PFS, supportive quality of life data, and favorable safety profile – demonstrate the clinical benefit of IVO in advanced m IDH1 CCA. Clinical trial information: NCT02989857.

Health-related quality-of-life (HRQoL) analysis from a randomized phase II trial of androgen signaling inhibitors with or without androgen deprivation therapy (ADT) for castration-sensitive prostate cancer: LACOG 0415.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 64-64
Author(s):  
Andrey Soares ◽  
Diogo Assed Bastos ◽  
Fabio A. B. Schutz ◽  
Eduardo Cronemberger ◽  
Murilo Luz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Locally Advanced ◽  
Patient Reported Outcome ◽  
Abiraterone Acetate ◽  
Outcome Data ◽  
Rank Test ◽  
Emotional Wellbeing ◽  
Patient Reported ◽  
Related Quality

64 Background: LACOG0415 is a 3-arm randomized trial evaluating ADT with abiraterone acetate plus prednisone (ADT+AAP), apalutamide alone (APA) or apalutamide with AAP (APA+AAP) for patients with locally-advanced, high-risk biochemical recurrence or metastatic castration-sensitive prostate cancer (ASCO 2020). In this trial, ADT+AAP and APA+AAP achieved the primary endpoint of percentage of patients with PSA ≤ 0.2 ng/mL at week 25. Apalutamide alone showed a high PSA decline > 50% rate, but did not achieve the pre-specified PSA threshold. Here we report patient-reported outcome data using Functional Assessment of Cancer Therapy-Prostate (FACT-P). Methods: HRQoL was measured in the overall population using the FACT-P questionnaire, comprising 5 subscales: physical wellbeing (PWB), functional wellbeing (FWB), emotional wellbeing (EWB), social/family wellbeing (SFWB), and prostate cancer subscale (PCS). Scores for each patient were measured at baseline and every four weeks until week 25. Questionnaire completion was defined as ≥ 1 question answered at an assessment time point. Analysis of HRQoL change from baseline and deterioration included only patients with baseline and ≥ 1 postbaseline score. Differences greater than 10-points in FACT-P total score and differences greater than 3-points in PWB, FWB, EWB, SFWB, and PCS scores were considered clinically significant. The time-to-event endpoint was estimated by Kaplan-Meier method and compared by stratified log-rank test. Results: 128 patients were included in LACOG0415 trial and 122 of them completed the HRQoL assessments (ranging from 95.3% at baseline to 79.7% at week 25). FACT-P and all subscales scores were similar for all three arms at baseline. There were no meaningful differences in FACT-P scores at baseline and at week 25 between the 3 arms. The subscales scores also showed no statistically differences at baseline and at week 25. Time to FACT-P deterioration did not show any statistically difference between three arms ( P=0.3371). Conclusions: ADT free alternatives with APA alone or APA+AAP did not show meaningful differences in HRQoL in patients with advanced castration-sensitive prostate cancer compared to ADT+AAP. The short follow-up period limited the ability to explore differences in HRQoL after 25 weeks. Larger studies with longer follow-up are needed to further evaluate HRQoL with ADT-free strategies. Clinical trial information: NCT02867020. [Table: see text]

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