A Randomized, Phase III Trial to Evaluate Rucaparib Monotherapy as Maintenance Treatment in Patients With Newly Diagnosed Ovarian Cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45)
PURPOSE: ATHENA (ClinicalTrials.gov identifier: NCT03522246) was designed to evaluate rucaparib first-line maintenance treatment in a broad patient population, including those without BRCA1 or BRCA2 (BRCA) mutations or other evidence of homologous recombination deficiency (HRD), or high-risk clinical characteristics such as residual disease. We report the results from the ATHENA-MONO comparison of rucaparib versus placebo.
METHODS: Patients with stage III-IV high-grade ovarian cancer undergoing surgical cytoreduction (R0/complete resection permitted) and responding to first-line platinum-doublet chemotherapy were randomly assigned 4:1 to oral rucaparib 600 mg twice a day or placebo. Stratification factors were HRD test status, residual disease after chemotherapy, and timing of surgery. The primary end point of investigator-assessed progression-free survival was assessed in a step-down procedure, first in the HRD population (BRCA-mutant or BRCA wild-type/loss of heterozygosity high tumor), and then in the intent-to-treat population.
RESULTS: As of March 23, 2022 (data cutoff), 427 and 111 patients were randomly assigned to rucaparib or placebo, respectively (HRD population: 185 v 49). Median progression-free survival (95% CI) was 28.7 months (23.0 to not reached) with rucaparib versus 11.3 months (9.1 to 22.1) with placebo in the HRD population (log-rank P = .0004; hazard ratio [HR], 0.47; 95% CI, 0.31 to 0.72); 20.2 months (15.2 to 24.7) versus 9.2 months (8.3 to 12.2) in the intent-to-treat population (log-rank P < .0001; HR, 0.52; 95% CI, 0.40 to 0.68); and 12.1 months (11.1 to 17.7) versus 9.1 months (4.0 to 12.2) in the HRD-negative population (HR, 0.65; 95% CI, 0.45 to 0.95). The most common grade ≥ 3 treatment-emergent adverse events were anemia (rucaparib, 28.7% v placebo, 0%) and neutropenia (14.6% v 0.9%).
CONCLUSION: Rucaparib monotherapy is effective as first-line maintenance, conferring significant benefit versus placebo in patients with advanced ovarian cancer with and without HRD.
| Errataetall: |
CommentIn: J Clin Oncol. 2023 Feb 1;41(4):935-936. - PMID 36201722 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:40 |
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| Enthalten in: |
Journal of clinical oncology : official journal of the American Society of Clinical Oncology - 40(2022), 34 vom: 01. Dez., Seite 3952-3964 |
| Sprache: |
Englisch |
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| Links: |
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| Themen: |
8237F3U7EH |
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| Anmerkungen: |
Date Completed 30.11.2022 Date Revised 12.10.2023 published: Print-Electronic ClinicalTrials.gov: NCT03522246 CommentIn: J Clin Oncol. 2023 Feb 1;41(4):935-936. - PMID 36201722 Citation Status MEDLINE |
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| doi: |
10.1200/JCO.22.01003 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM34180407X |
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| 100 | 1 | |a Monk, Bradley J |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A Randomized, Phase III Trial to Evaluate Rucaparib Monotherapy as Maintenance Treatment in Patients With Newly Diagnosed Ovarian Cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45) |
| 264 | 1 | |c 2022 | |
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| 500 | |a Date Completed 30.11.2022 | ||
| 500 | |a Date Revised 12.10.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT03522246 | ||
| 500 | |a CommentIn: J Clin Oncol. 2023 Feb 1;41(4):935-936. - PMID 36201722 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a PURPOSE: ATHENA (ClinicalTrials.gov identifier: NCT03522246) was designed to evaluate rucaparib first-line maintenance treatment in a broad patient population, including those without BRCA1 or BRCA2 (BRCA) mutations or other evidence of homologous recombination deficiency (HRD), or high-risk clinical characteristics such as residual disease. We report the results from the ATHENA-MONO comparison of rucaparib versus placebo | ||
| 520 | |a METHODS: Patients with stage III-IV high-grade ovarian cancer undergoing surgical cytoreduction (R0/complete resection permitted) and responding to first-line platinum-doublet chemotherapy were randomly assigned 4:1 to oral rucaparib 600 mg twice a day or placebo. Stratification factors were HRD test status, residual disease after chemotherapy, and timing of surgery. The primary end point of investigator-assessed progression-free survival was assessed in a step-down procedure, first in the HRD population (BRCA-mutant or BRCA wild-type/loss of heterozygosity high tumor), and then in the intent-to-treat population | ||
| 520 | |a RESULTS: As of March 23, 2022 (data cutoff), 427 and 111 patients were randomly assigned to rucaparib or placebo, respectively (HRD population: 185 v 49). Median progression-free survival (95% CI) was 28.7 months (23.0 to not reached) with rucaparib versus 11.3 months (9.1 to 22.1) with placebo in the HRD population (log-rank P = .0004; hazard ratio [HR], 0.47; 95% CI, 0.31 to 0.72); 20.2 months (15.2 to 24.7) versus 9.2 months (8.3 to 12.2) in the intent-to-treat population (log-rank P < .0001; HR, 0.52; 95% CI, 0.40 to 0.68); and 12.1 months (11.1 to 17.7) versus 9.1 months (4.0 to 12.2) in the HRD-negative population (HR, 0.65; 95% CI, 0.45 to 0.95). The most common grade ≥ 3 treatment-emergent adverse events were anemia (rucaparib, 28.7% v placebo, 0%) and neutropenia (14.6% v 0.9%) | ||
| 520 | |a CONCLUSION: Rucaparib monotherapy is effective as first-line maintenance, conferring significant benefit versus placebo in patients with advanced ovarian cancer with and without HRD | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Clinical Trial, Phase III | |
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