NRG-GY012 : Randomized phase 2 study comparing olaparib, cediranib, and the combination of cediranib/olaparib in women with recurrent, persistent, or metastatic endometrial cancer
© 2023 American Cancer Society..
PURPOSE: This paper reports the efficacy of the poly (ADP-ribose) polymerase inhibitor olaparib alone and in combination with the antiangiogenesis agent cediranib compared with cediranib alone in patients with advanced endometrial cancer.
METHODS: This was open-label, randomized, phase 2 trial (NCT03660826). Eligible patients had recurrent endometrial cancer, received at least one (<3) prior lines of chemotherapy, and were Eastern Cooperative Oncology Group performance status 0 to 2. Patients were randomly assigned (1:1:1), stratified by histology (serous vs. other) to receive cediranib alone (reference arm), olaparib, or olaparib and cediranib for 28-day cycles until progression or unacceptable toxicity. The primary end point was progression-free survival in the intention-to-treat population. Homologous repair deficiency was explored using the BROCA-GO sequencing panel.
RESULTS: A total of 120 patients were enrolled and all were included in the intention-to-treat analysis. Median age was 66 (range, 41-86) years and 47 (39.2%) had serous histology. Median progression-free survival for cediranib was 3.8 months compared with 2.0 months for olaparib (hazard ratio, 1.45 [95% CI, 0.91-2.3] p = .935) and 5.5 months for olaparib/cediranib (hazard ratio, 0.7 [95% CI, 0.43-1.14] p = .064). Four patients receiving the combination had a durable response lasting more than 20 months. The most common grade 3/4 toxicities were hypertension in the cediranib (36%) and olaparib/cediranib (33%) arms, fatigue (20.5% olaparib/cediranib), and diarrhea (17.9% cediranib). The BROCA-GO panel results were not associated with response.
CONCLUSION: The combination of cediranib and olaparib demonstrated modest clinical efficacy; however, the primary end point of the study was not met. The combination was safe without unexpected toxicity.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:130 |
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| Enthalten in: |
Cancer - 130(2024), 8 vom: 15. März, Seite 1234-1245 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Rimel, Bobbie J [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 19.03.2024 Date Revised 22.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/cncr.35151 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM366181467 |
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| 100 | 1 | |a Rimel, Bobbie J |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a NRG-GY012 |b Randomized phase 2 study comparing olaparib, cediranib, and the combination of cediranib/olaparib in women with recurrent, persistent, or metastatic endometrial cancer |
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| 500 | |a Date Completed 19.03.2024 | ||
| 500 | |a Date Revised 22.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 American Cancer Society. | ||
| 520 | |a PURPOSE: This paper reports the efficacy of the poly (ADP-ribose) polymerase inhibitor olaparib alone and in combination with the antiangiogenesis agent cediranib compared with cediranib alone in patients with advanced endometrial cancer | ||
| 520 | |a METHODS: This was open-label, randomized, phase 2 trial (NCT03660826). Eligible patients had recurrent endometrial cancer, received at least one (<3) prior lines of chemotherapy, and were Eastern Cooperative Oncology Group performance status 0 to 2. Patients were randomly assigned (1:1:1), stratified by histology (serous vs. other) to receive cediranib alone (reference arm), olaparib, or olaparib and cediranib for 28-day cycles until progression or unacceptable toxicity. The primary end point was progression-free survival in the intention-to-treat population. Homologous repair deficiency was explored using the BROCA-GO sequencing panel | ||
| 520 | |a RESULTS: A total of 120 patients were enrolled and all were included in the intention-to-treat analysis. Median age was 66 (range, 41-86) years and 47 (39.2%) had serous histology. Median progression-free survival for cediranib was 3.8 months compared with 2.0 months for olaparib (hazard ratio, 1.45 [95% CI, 0.91-2.3] p = .935) and 5.5 months for olaparib/cediranib (hazard ratio, 0.7 [95% CI, 0.43-1.14] p = .064). Four patients receiving the combination had a durable response lasting more than 20 months. The most common grade 3/4 toxicities were hypertension in the cediranib (36%) and olaparib/cediranib (33%) arms, fatigue (20.5% olaparib/cediranib), and diarrhea (17.9% cediranib). The BROCA-GO panel results were not associated with response | ||
| 520 | |a CONCLUSION: The combination of cediranib and olaparib demonstrated modest clinical efficacy; however, the primary end point of the study was not met. The combination was safe without unexpected toxicity | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
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| 650 | 7 | |a Indoles |2 NLM | |
| 650 | 7 | |a Piperazines |2 NLM | |
| 650 | 7 | |a Quinazolines |2 NLM | |
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| 700 | 1 | |a Borowsky, Mark |e verfasserin |4 aut | |
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| 700 | 1 | |a Backes, Floor |e verfasserin |4 aut | |
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| 700 | 1 | |a Powell, Matthew |e verfasserin |4 aut | |
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