Association of location of BRCA1 and BRCA2 mutations with benefit from olaparib and bevacizumab maintenance in high-grade ovarian cancer : phase III PAOLA-1/ENGOT-ov25 trial subgroup exploratory analysis
Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved..
BACKGROUND: In the phase III PAOLA-1 study, the addition of maintenance olaparib to bevacizumab in patients with newly diagnosed high-grade ovarian cancer (HGOC) resulted in prolonged progression-free survival (PFS), particularly for homologous recombination deficiency-positive tumors, including those with a BRCA mutation (BRCAm). The magnitude of benefit from olaparib and bevacizumab according to the location of mutation in BRCA1/BRCA2 remains to be explored.
PATIENTS AND METHODS: Patients with advanced-stage HGOC responding after platinum-based chemotherapy + bevacizumab received maintenance therapy bevacizumab (15 mg/kg q3w for 15 months) + either olaparib (300 mg b.i.d. for 24 months) or placebo. PFS was analyzed in the subgroup of patients with BRCA1m/BRCA2m according to mutation location in the functional domains of BRCA1 [Really Interesting Gene (RING), DNA-binding domain (DBD), or C-terminal domain of BRCA1 (BRCT)] and BRCA2 [RAD51-binding domain (RAD51-BD); DBD].
RESULTS: From 806 randomized patients, 159 harbored BRCA1m (19.7%) and 74 BRCA2m (9.2%). BRCA1m in RING, DBD, and BRCT domains was detected in 18, 40, and 33 patients, and BRCA2m in RAD51-BD and DBD in 36 and 13 patients, respectively. After a median follow-up of 25.5 months, benefit from maintenance olaparib + bevacizumab was observed irrespective of location of BRCAm. The benefit was particularly high for those with BRCA1m located in the DBD, with 24-month PFS estimated to be 89% and 15% [olaparib + bevacizumab versus placebo + bevacizumab hazard ratio = 0.08 (95% confidence interval 0.02-0.28); interaction P = 0.03]. In BRCA2m patients, 24-month PFS rates for those with mutations located in the DBD were 90% and 100% (olaparib + bevacizumab versus placebo + bevacizumab), respectively.
CONCLUSIONS: Advanced-stage BRCA-mutated HGOC patients reported PFS benefit from maintenance olaparib and bevacizumab regardless of mutation location. The benefit is particularly high for patients with mutations located in the DBD of BRCA1. Mutations located in the DBD of BRCA2 are also associated with excellent outcome.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:34 |
|---|---|
| Enthalten in: |
Annals of oncology : official journal of the European Society for Medical Oncology - 34(2023), 2 vom: 16. Feb., Seite 152-162 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Labidi-Galy, S I [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 07.02.2023 Date Revised 10.02.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.annonc.2022.11.003 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM350757925 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM350757925 | ||
| 003 | DE-627 | ||
| 005 | 20231226045722.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.annonc.2022.11.003 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1169.xml |
| 035 | |a (DE-627)NLM350757925 | ||
| 035 | |a (NLM)36564284 | ||
| 035 | |a (PII)S0923-7534(22)04733-0 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Labidi-Galy, S I |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Association of location of BRCA1 and BRCA2 mutations with benefit from olaparib and bevacizumab maintenance in high-grade ovarian cancer |b phase III PAOLA-1/ENGOT-ov25 trial subgroup exploratory analysis |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 07.02.2023 | ||
| 500 | |a Date Revised 10.02.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved. | ||
| 520 | |a BACKGROUND: In the phase III PAOLA-1 study, the addition of maintenance olaparib to bevacizumab in patients with newly diagnosed high-grade ovarian cancer (HGOC) resulted in prolonged progression-free survival (PFS), particularly for homologous recombination deficiency-positive tumors, including those with a BRCA mutation (BRCAm). The magnitude of benefit from olaparib and bevacizumab according to the location of mutation in BRCA1/BRCA2 remains to be explored | ||
| 520 | |a PATIENTS AND METHODS: Patients with advanced-stage HGOC responding after platinum-based chemotherapy + bevacizumab received maintenance therapy bevacizumab (15 mg/kg q3w for 15 months) + either olaparib (300 mg b.i.d. for 24 months) or placebo. PFS was analyzed in the subgroup of patients with BRCA1m/BRCA2m according to mutation location in the functional domains of BRCA1 [Really Interesting Gene (RING), DNA-binding domain (DBD), or C-terminal domain of BRCA1 (BRCT)] and BRCA2 [RAD51-binding domain (RAD51-BD); DBD] | ||
| 520 | |a RESULTS: From 806 randomized patients, 159 harbored BRCA1m (19.7%) and 74 BRCA2m (9.2%). BRCA1m in RING, DBD, and BRCT domains was detected in 18, 40, and 33 patients, and BRCA2m in RAD51-BD and DBD in 36 and 13 patients, respectively. After a median follow-up of 25.5 months, benefit from maintenance olaparib + bevacizumab was observed irrespective of location of BRCAm. The benefit was particularly high for those with BRCA1m located in the DBD, with 24-month PFS estimated to be 89% and 15% [olaparib + bevacizumab versus placebo + bevacizumab hazard ratio = 0.08 (95% confidence interval 0.02-0.28); interaction P = 0.03]. In BRCA2m patients, 24-month PFS rates for those with mutations located in the DBD were 90% and 100% (olaparib + bevacizumab versus placebo + bevacizumab), respectively | ||
| 520 | |a CONCLUSIONS: Advanced-stage BRCA-mutated HGOC patients reported PFS benefit from maintenance olaparib and bevacizumab regardless of mutation location. The benefit is particularly high for patients with mutations located in the DBD of BRCA1. Mutations located in the DBD of BRCA2 are also associated with excellent outcome | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a BRCA mutation | |
| 650 | 4 | |a PARP inhibitor | |
| 650 | 4 | |a genotype | |
| 650 | 4 | |a location of mutation | |
| 650 | 4 | |a olaparib | |
| 650 | 4 | |a ovarian cancer | |
| 650 | 4 | |a type of mutation | |
| 650 | 7 | |a Bevacizumab |2 NLM | |
| 650 | 7 | |a 2S9ZZM9Q9V |2 NLM | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a olaparib |2 NLM | |
| 650 | 7 | |a WOH1JD9AR8 |2 NLM | |
| 650 | 7 | |a BRCA1 Protein |2 NLM | |
| 650 | 7 | |a Phthalazines |2 NLM | |
| 650 | 7 | |a BRCA1 protein, human |2 NLM | |
| 650 | 7 | |a BRCA2 protein, human |2 NLM | |
| 650 | 7 | |a BRCA2 Protein |2 NLM | |
| 700 | 1 | |a Rodrigues, M |e verfasserin |4 aut | |
| 700 | 1 | |a Sandoval, J L |e verfasserin |4 aut | |
| 700 | 1 | |a Kurtz, J E |e verfasserin |4 aut | |
| 700 | 1 | |a Heitz, F |e verfasserin |4 aut | |
| 700 | 1 | |a Mosconi, A M |e verfasserin |4 aut | |
| 700 | 1 | |a Romero, I |e verfasserin |4 aut | |
| 700 | 1 | |a Denison, U |e verfasserin |4 aut | |
| 700 | 1 | |a Nagao, S |e verfasserin |4 aut | |
| 700 | 1 | |a Vergote, I |e verfasserin |4 aut | |
| 700 | 1 | |a Parma, G |e verfasserin |4 aut | |
| 700 | 1 | |a Nøttrup, T J |e verfasserin |4 aut | |
| 700 | 1 | |a Rouleau, E |e verfasserin |4 aut | |
| 700 | 1 | |a Garnier, G |e verfasserin |4 aut | |
| 700 | 1 | |a El-Balat, A |e verfasserin |4 aut | |
| 700 | 1 | |a Zamagni, C |e verfasserin |4 aut | |
| 700 | 1 | |a Martín-Lorente, C |e verfasserin |4 aut | |
| 700 | 1 | |a Pujade-Lauraine, E |e verfasserin |4 aut | |
| 700 | 1 | |a Fiévet, A |e verfasserin |4 aut | |
| 700 | 1 | |a Ray-Coquard, I L |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Annals of oncology : official journal of the European Society for Medical Oncology |d 1990 |g 34(2023), 2 vom: 16. Feb., Seite 152-162 |w (DE-627)NLM012606308 |x 1569-8041 |7 nnns |
| 773 | 1 | 8 | |g volume:34 |g year:2023 |g number:2 |g day:16 |g month:02 |g pages:152-162 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.annonc.2022.11.003 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 34 |j 2023 |e 2 |b 16 |c 02 |h 152-162 | ||