Veliparib monotherapy following carboplatin/paclitaxel plus veliparib combination therapy in patients with germline BRCA-associated advanced breast cancer : results of exploratory analyses from the phase III BROCADE3 trial
Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved..
BACKGROUND: In the BROCADE3 trial, addition of the poly(ADP-ribose) polymerase inhibitor, veliparib, to carboplatin/paclitaxel improved progression-free survival (PFS) (hazard ratio 0.71, 95% confidence interval 0.57-0.88; P = 0.002) in patients with advanced human epidermal growth factor receptor 2-negative, germline BRCA1/2-mutated breast cancer. A subset of patients discontinued both carboplatin and paclitaxel before progression and continued on veliparib/placebo maintenance monotherapy until progression. Analyses in this patient subgroup are reported.
PATIENTS AND METHODS: Patients were randomized 2 : 1 to veliparib plus carboplatin/paclitaxel or placebo plus carboplatin/paclitaxel. Veliparib (120 mg twice daily) or placebo was given on days -2 to 5, carboplatin (area under the curve 6 mg/ml) on day 1, and paclitaxel (80 mg/m2) on days 1, 8, and 15 of 21-day cycles. Patients who discontinued both carboplatin and paclitaxel before progression received blinded study drug monotherapy at an increased dose of 300-400 mg twice daily continuously. PFS was the primary endpoint. Exploratory analyses were carried out in the subgroup of patients who received blinded study drug as monotherapy. A time-varying Cox model including data from all patients was also used to evaluate treatment effect in the combination and monotherapy phases.
RESULTS: A total of 136 of 337 patients randomized to veliparib plus carboplatin/paclitaxel and 58/172 patients randomized to placebo plus carboplatin/paclitaxel discontinued both carboplatin and paclitaxel before progression and continued on blinded veliparib or placebo monotherapy. In this blinded monotherapy subgroup, investigator-assessed median PFS from randomization was 25.7 months with veliparib versus 14.6 months with placebo. Hazard ratios from a time-varying Cox model favored veliparib during both combination therapy and monotherapy. Any-grade adverse events occurring in the monotherapy phase were primarily gastrointestinal. The most common grade ≥3 adverse events were neutropenia and anemia (4% each with veliparib; 5% and 2%, respectively, with placebo).
CONCLUSIONS: Veliparib maintenance monotherapy had a tolerable safety profile and may extend PFS following combination chemotherapy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:33 |
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| Enthalten in: |
Annals of oncology : official journal of the European Society for Medical Oncology - 33(2022), 3 vom: 01. März, Seite 299-309 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Han, H S [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 03.03.2022 Date Revised 03.03.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.annonc.2021.11.018 |
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| Förderinstitution / Projekttitel: |
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NLM333981243 |
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| 100 | 1 | |a Han, H S |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Veliparib monotherapy following carboplatin/paclitaxel plus veliparib combination therapy in patients with germline BRCA-associated advanced breast cancer |b results of exploratory analyses from the phase III BROCADE3 trial |
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| 500 | |a Date Revised 03.03.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved. | ||
| 520 | |a BACKGROUND: In the BROCADE3 trial, addition of the poly(ADP-ribose) polymerase inhibitor, veliparib, to carboplatin/paclitaxel improved progression-free survival (PFS) (hazard ratio 0.71, 95% confidence interval 0.57-0.88; P = 0.002) in patients with advanced human epidermal growth factor receptor 2-negative, germline BRCA1/2-mutated breast cancer. A subset of patients discontinued both carboplatin and paclitaxel before progression and continued on veliparib/placebo maintenance monotherapy until progression. Analyses in this patient subgroup are reported | ||
| 520 | |a PATIENTS AND METHODS: Patients were randomized 2 : 1 to veliparib plus carboplatin/paclitaxel or placebo plus carboplatin/paclitaxel. Veliparib (120 mg twice daily) or placebo was given on days -2 to 5, carboplatin (area under the curve 6 mg/ml) on day 1, and paclitaxel (80 mg/m2) on days 1, 8, and 15 of 21-day cycles. Patients who discontinued both carboplatin and paclitaxel before progression received blinded study drug monotherapy at an increased dose of 300-400 mg twice daily continuously. PFS was the primary endpoint. Exploratory analyses were carried out in the subgroup of patients who received blinded study drug as monotherapy. A time-varying Cox model including data from all patients was also used to evaluate treatment effect in the combination and monotherapy phases | ||
| 520 | |a RESULTS: A total of 136 of 337 patients randomized to veliparib plus carboplatin/paclitaxel and 58/172 patients randomized to placebo plus carboplatin/paclitaxel discontinued both carboplatin and paclitaxel before progression and continued on blinded veliparib or placebo monotherapy. In this blinded monotherapy subgroup, investigator-assessed median PFS from randomization was 25.7 months with veliparib versus 14.6 months with placebo. Hazard ratios from a time-varying Cox model favored veliparib during both combination therapy and monotherapy. Any-grade adverse events occurring in the monotherapy phase were primarily gastrointestinal. The most common grade ≥3 adverse events were neutropenia and anemia (4% each with veliparib; 5% and 2%, respectively, with placebo) | ||
| 520 | |a CONCLUSIONS: Veliparib maintenance monotherapy had a tolerable safety profile and may extend PFS following combination chemotherapy | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a BRCA | |
| 650 | 4 | |a BROCADE3 | |
| 650 | 4 | |a PARP inhibitor | |
| 650 | 4 | |a metastatic breast cancer | |
| 650 | 4 | |a veliparib | |
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| 700 | 1 | |a Arun, B K |e verfasserin |4 aut | |
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| 700 | 1 | |a Friedlander, M |e verfasserin |4 aut | |
| 700 | 1 | |a Ayoub, J P |e verfasserin |4 aut | |
| 700 | 1 | |a Puhalla, S L |e verfasserin |4 aut | |
| 700 | 1 | |a Bach, B A |e verfasserin |4 aut | |
| 700 | 1 | |a Kundu, M G |e verfasserin |4 aut | |
| 700 | 1 | |a Khandelwal, N |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, D |e verfasserin |4 aut | |
| 700 | 1 | |a Bhattacharya, S |e verfasserin |4 aut | |
| 700 | 1 | |a Maag, D |e verfasserin |4 aut | |
| 700 | 1 | |a Ratajczak, C K |e verfasserin |4 aut | |
| 700 | 1 | |a Diéras, V |e verfasserin |4 aut | |
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