Patient-reported outcomes with olaparib plus abiraterone versus placebo plus abiraterone for metastatic castration- resistant prostate cancer: a randomised, double-blind, phase 2 trial

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F22%3A00079089" target="_blank" >RIV/00209805:_____/22:00079089 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.clinicalkey.com/service/content/pdf/watermarked/1-s2.0-S1470204522004983.pdf?locale=en_US&searchIndex=" target="_blank" >https://www.clinicalkey.com/service/content/pdf/watermarked/1-s2.0-S1470204522004983.pdf?locale=en_US&searchIndex=</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/S1470-2045(22)00498-3" target="_blank" >10.1016/S1470-2045(22)00498-3</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Patient-reported outcomes with olaparib plus abiraterone versus placebo plus abiraterone for metastatic castration- resistant prostate cancer: a randomised, double-blind, phase 2 trial

Popis výsledku v původním jazyce

Background Results of this double-blind, phase 2 trial showed patients with metastatic castration-resistant prostate cancer given olaparib plus abiraterone versus placebo plus abiraterone had significantly improved progression-free survival. Here, we present an exploratory analysis of pain and health-related quality of life (HRQOL).Methods This double-blind, randomised, placebo-controlled, phase 2 trial was conducted across 41 urological oncology sites in 11 countries in Europe and North America. Eligible patients were aged 18 years or older, had metastatic castration-resistant prostate cancer, and had previously received docetaxel and up to one additional line of previous chemotherapy. Metastatic castration-resistant prostate cancer was defined as increasing prostate-specific antigen (PSA) concentration or other signs of disease progression despite androgen-deprivation therapy and serum testosterone concentrations at castrate levels (&lt;= 50 ng/dL), and with at least one metastatic lesion on bone scan, CT, or MRI. Eligible patients were randomly assigned (1:1) to receive oral olaparib (300 mg twice per day) plus oral abiraterone (1000 mg once a day) and oral prednisone or prednisolone (5 mg twice a day) or placebo plus abiraterone (1000 mg once a day) and prednisone or prednisolone (5 mg twice a day). Randomisation was done without stratification and by use of an interactive voice or web response system. A randomised treatment kit ID number was assigned sequentially to each patient as they became eligible. The primary endpoint (radiographic progression-free survival) has previously been reported. HRQOL was a prespecified exploratory patient-reported outcome. Patients were asked to complete the Brief Pain Inventory-Short Form (BPI-SF), single-item worst bone pain, Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire, and EuroQol-5 five-dimension five level (EQ-5D-5L) assessment at baseline, at weeks 4, 8, and 12, then every 12 weeks until treatment discontinuation. Prespecified outcomes were change from baseline in BPI-SF worst pain, single-item worst bone pain and FACT-P Total Outcome Index (TOI) scale scores, time to deterioration in BPI-SF worst pain and worst bone pain, and assessment of the EQ-5D-5L pain and discomfort domain. All analyses were exploratory and done in the full analysis set (all randomly assigned patients, including patients who were randomly assigned but did not subsequently go on to receive study treatment), with the exception of mean baseline and total change from baseline analyses, for which we used the population who had a valid baseline and at least one post-baseline assessment. This trial is registered with Clinicaltrials.gov, NCT01972217, and is no longer recruiting patients.Findings Between Nov 25, 2014, and July 14, 2015, 171 patients were assessed for eligibility. 29 patients were excluded, and 142 were enrolled and randomly assigned to receive olaparib and abiraterone (n=71) or placebo and abiraterone (n=71). Data cutoff was Sept 22, 2017. Median follow-up was 15middot9 months (IQR 8middot1-25middot5) in the olaparib plus abiraterone group and 24middot5 months (8middot1-27middot6) in the placebo plus abiraterone group. Questionnaire compliance was generally high (43-100%). Least-squares mean changes from baseline in BPI-SF worst pain, single-item worst bone pain, and FACT-P TOI remained stable across all visits for patients in both treatment groups. Adjusted mean change in FACT-P TOI from baseline across all visits was -0middot10 (95% CI -2middot50 to 2middot71) in the olaparib plus abiraterone group and -1middot20 (-4middot15 to 1middot74) in the placebo plus abiraterone group (difference 1middot30, 95% CI -2middot70 to 5middot30; p=0middot52). Time to deterioration in pain was similar in both groups (BPI-SF worst pain HR 0middot90 [95% CI 0middot62-1middot32], p=0middot30; worst bone pain HR 0middot85 [0middot59-1middot22], p=0middot18). Improvement rates in the pain and discomfort domain of the EQ-5D-5L were similar in both groups from baseline to week 48, beyond which a higher proportion of patients in the olaparib plus abiraterone arm reported an improvement compared to the placebo plus abiraterone group.Interpretation In these prespecified exploratory analyses, there was no significant difference in pain or HRQOL when olaparib was added to abiraterone. In this phase 2 trial, a statistically significant radiographic progression-free survival benefit was observed with the olaparib plus abiraterone combination. These results suggest that the improved survival benefits observed when combining olaparib with abiraterone does not result in different HRQOL compared with placebo plus abiraterone. Phase 3 studies are required to validate these results.Funding AstraZeneca and Merck Sharp &amp; Dohme, a subsidiary of Merck &amp; Co, Rahway, NJ, USA.Copyright (c) 2022 Published by Elsevier Ltd. All rights reserved.

Název v anglickém jazyce

Patient-reported outcomes with olaparib plus abiraterone versus placebo plus abiraterone for metastatic castration- resistant prostate cancer: a randomised, double-blind, phase 2 trial

Popis výsledku anglicky

Background Results of this double-blind, phase 2 trial showed patients with metastatic castration-resistant prostate cancer given olaparib plus abiraterone versus placebo plus abiraterone had significantly improved progression-free survival. Here, we present an exploratory analysis of pain and health-related quality of life (HRQOL).Methods This double-blind, randomised, placebo-controlled, phase 2 trial was conducted across 41 urological oncology sites in 11 countries in Europe and North America. Eligible patients were aged 18 years or older, had metastatic castration-resistant prostate cancer, and had previously received docetaxel and up to one additional line of previous chemotherapy. Metastatic castration-resistant prostate cancer was defined as increasing prostate-specific antigen (PSA) concentration or other signs of disease progression despite androgen-deprivation therapy and serum testosterone concentrations at castrate levels (&lt;= 50 ng/dL), and with at least one metastatic lesion on bone scan, CT, or MRI. Eligible patients were randomly assigned (1:1) to receive oral olaparib (300 mg twice per day) plus oral abiraterone (1000 mg once a day) and oral prednisone or prednisolone (5 mg twice a day) or placebo plus abiraterone (1000 mg once a day) and prednisone or prednisolone (5 mg twice a day). Randomisation was done without stratification and by use of an interactive voice or web response system. A randomised treatment kit ID number was assigned sequentially to each patient as they became eligible. The primary endpoint (radiographic progression-free survival) has previously been reported. HRQOL was a prespecified exploratory patient-reported outcome. Patients were asked to complete the Brief Pain Inventory-Short Form (BPI-SF), single-item worst bone pain, Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire, and EuroQol-5 five-dimension five level (EQ-5D-5L) assessment at baseline, at weeks 4, 8, and 12, then every 12 weeks until treatment discontinuation. Prespecified outcomes were change from baseline in BPI-SF worst pain, single-item worst bone pain and FACT-P Total Outcome Index (TOI) scale scores, time to deterioration in BPI-SF worst pain and worst bone pain, and assessment of the EQ-5D-5L pain and discomfort domain. All analyses were exploratory and done in the full analysis set (all randomly assigned patients, including patients who were randomly assigned but did not subsequently go on to receive study treatment), with the exception of mean baseline and total change from baseline analyses, for which we used the population who had a valid baseline and at least one post-baseline assessment. This trial is registered with Clinicaltrials.gov, NCT01972217, and is no longer recruiting patients.Findings Between Nov 25, 2014, and July 14, 2015, 171 patients were assessed for eligibility. 29 patients were excluded, and 142 were enrolled and randomly assigned to receive olaparib and abiraterone (n=71) or placebo and abiraterone (n=71). Data cutoff was Sept 22, 2017. Median follow-up was 15middot9 months (IQR 8middot1-25middot5) in the olaparib plus abiraterone group and 24middot5 months (8middot1-27middot6) in the placebo plus abiraterone group. Questionnaire compliance was generally high (43-100%). Least-squares mean changes from baseline in BPI-SF worst pain, single-item worst bone pain, and FACT-P TOI remained stable across all visits for patients in both treatment groups. Adjusted mean change in FACT-P TOI from baseline across all visits was -0middot10 (95% CI -2middot50 to 2middot71) in the olaparib plus abiraterone group and -1middot20 (-4middot15 to 1middot74) in the placebo plus abiraterone group (difference 1middot30, 95% CI -2middot70 to 5middot30; p=0middot52). Time to deterioration in pain was similar in both groups (BPI-SF worst pain HR 0middot90 [95% CI 0middot62-1middot32], p=0middot30; worst bone pain HR 0middot85 [0middot59-1middot22], p=0middot18). Improvement rates in the pain and discomfort domain of the EQ-5D-5L were similar in both groups from baseline to week 48, beyond which a higher proportion of patients in the olaparib plus abiraterone arm reported an improvement compared to the placebo plus abiraterone group.Interpretation In these prespecified exploratory analyses, there was no significant difference in pain or HRQOL when olaparib was added to abiraterone. In this phase 2 trial, a statistically significant radiographic progression-free survival benefit was observed with the olaparib plus abiraterone combination. These results suggest that the improved survival benefits observed when combining olaparib with abiraterone does not result in different HRQOL compared with placebo plus abiraterone. Phase 3 studies are required to validate these results.Funding AstraZeneca and Merck Sharp &amp; Dohme, a subsidiary of Merck &amp; Co, Rahway, NJ, USA.Copyright (c) 2022 Published by Elsevier Ltd. All rights reserved.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Lancet Oncology

ISSN

1470-2045

e-ISSN

1474-5488

Svazek periodika

23

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

1297-1307

Kód UT WoS článku

000878568900032

EID výsledku v databázi Scopus

2-s2.0-85138460202