Meeting
2021 ASCO Annual Meeting
Progression-free survival (PFS) and second PFS (PFS2) by disease stage in patients (pts) with homologous recombination deficiency (HRD)-positive newly diagnosed advanced ovarian cancer receiving bevacizumab (bev) with olaparib/placebo maintenance in the phase III PAOLA-1/ENGOT-ov25 trial.
Authors
Patricia Pautier
Institut Gustave Roussy, and GINECO, Villejuif, France
Patricia Pautier , Philipp Harter , Carmela Pisano , Claire Cropet , Susana Hernando Polo , Regina Berger , Takashi Matsumoto , Ignace Vergote , Nicoletta Colombo , Trine Jakobi Noettrup , Georges Garnier , Peter Hillemanns , Claudio Zamagni , Antonio Gonzalez Martin , Claudia Lefeuvre-Plesse , Dominik Denschlag , Alain Lortholary , Jalid Sehouli , Frederic Selle , Isabelle Laure Ray-Coquard
Organizations
Institut Gustave Roussy, and GINECO, Villejuif, France, Evang Kliniken Essen-Mitte, and AGO, Essen, Germany, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", and MITO, Naples, Italy, Centre Léon Bérard, Lyon, France, Hospital Universitario Fundación Alcorcón, and GEICO, Madrid, Spain, Medical University of Innsbruck, Department for Gynecology and Obstetrics, and AGO-Austria, Innsbruck, Austria, Ehime University Hospital and GOTIC, Toon, Japan, University Hospitals Leuven, Leuven Cancer Institute, and BGOG, Leuven, Belgium, Istituto Europeo Oncologia IRCCS, and MANGO, Milan, Italy, Copenhagen University Hospital, and NSGO, Copenhagen, Denmark, Centre Hospitalier Princesse Grace, and GINECO, Monaco, Monaco, Medizinische Hochschule Hannover, and AGO, Hannover, Germany, IRCCS Policlinico di S.Orsola, and MITO, Bologna, Italy, Clínica Universidad de Navarra, and GEICO, Madrid, Spain, Centre Eugène Marquis, and GINECO, Rennes, France, Hochtaunuskliniken, and AGO, Bad Homburg Vor Der Höhe, Germany, Hôpital Privé du Confluent, and GINECO, Nantes, France, Charité–Universitätsmedizin Berlin (CVK), and AGO, Berlin, Germany, Groupe Hospitalier Diaconesses Croix Saint-Simon, and GINECO, Paris, France, Centre Léon Bérard, and GINECO, Lyon, France
Research Funding
Pharmaceutical/Biotech Company
AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA
Background: In the Phase III PAOLA-1/ENGOT-ov25 trial (NCT02477644), the addition of maintenance olaparib to bev in pts with newly diagnosed advanced high-grade ovarian cancer (HGOC) resulted in a significant PFS benefit, particularly in HRD-positive (HRD+) pts (hazard ratio [HR] 0.33; 95% CI 0.25–0.45) (Ray-Coquard et al.NEJM 2019). We explored efficacy in HRD+ pts by disease stage. Methods: Pts with newly diagnosed, FIGO stage III–IV HGOC in response after platinum-based chemotherapy + bev received bev (15 mg/kg q3w for 15 months [mo]) + either olaparib (300 mg bid for 24 mo) or placebo (pbo). This exploratory analysis evaluated PFS (data cut-off [DCO]: Mar 22 2019) and PFS2 (DCO: Mar 22 2020) in HRD+ pts (tumor BRCA1/BRCA2 mutation [tBRCAm] or genomic instability score [Myriad myChoice HRD Plus] ≥42) by FIGO stage. Results: 387/806 randomized pts (48%) were HRD+; 272/387 (70%) had stage III disease and 115/387 (30%) had stage IV disease. 153 (56%) HRD+ stage III pts and 61 (53%) HRD+ stage IV pts had a tBRCAm. Among HRD+ stage III pts, 172 (63%) had upfront surgery (51/172 [30%] had residual disease) and 90 (33%) had interval surgery (19/90 [21%] had residual disease); 52 (45%) HRD+ stage IV pts had upfront surgery (34/52 [65%] had residual disease) and 55 (48%) had interval surgery (18/55 [33%] had residual disease). Median follow-up for PFS and PFS2 was respectively 24.8 and 37.2 mo in HRD+ stage III pts and 24.0 and 37.0 mo in HRD+ stage IV pts. Median PFS, PFS2 and HRs are in the Table. Among HRD+ stage III pts, 36-mo PFS2 (olaparib + bev vs pbo + bev) was 74% vs 60%; among HRD+ stage IV pts, 53% vs 30%. Among HRD+ stage III pts with no residual disease after upfront surgery, HR (95% CI) for PFS was 0.15 (0.07–0.30) and for PFS2 was 0.22 (0.06–0.67). Among HRD+ stage III pts with residual disease after upfront surgery or who received neoadjuvant chemotherapy, or HRD+ stage IV pts, HR (95% CI) for PFS was 0.38 (0.27–0.53) and PFS2 was 0.68 (0.46–1.03). Conclusions: In the PAOLA-1 study, maintenance olaparib + bev provided a PFS and PFS2 benefit over pbo + bev in HRD+ pts, irrespective of FIGO stage and residual disease after upfront surgery. Clinical trial information: NCT02477644
| Olaparib + bev | Pbo + bev | HR (95% CI) | |
|---|---|---|---|
| Median PFS, mo (95% CI) | |||
| Stage III | 39.3 (36.0–NE) (n=182) | 19.9 (17.7–23.4) (n=90) | 0.32 (0.22–0.47) |
| Stage IV | 25.1 (22.0–37.2) (n=73) | 12.8 (10.4–15.8) (n=42) | 0.32 (0.20–0.52) |
| Median PFS2, mo (95% CI) | HR (95% CI) | ||
| Stage III | NE (50.3–NE) (n=182) | 43.0 (35.3–NE) (n=90) | 0.57 (0.38–0.87) |
| Stage IV | 37.8 (29.7–NE) (n=73) | 25.6 (22.6–35.2) (n=42) | 0.56 (0.35–0.91) |
NE, not estimable.
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Abstract Details
Session Type
Poster Discussion Session
Session Title
Gynecologic Cancer
Track
Gynecologic Cancer
Sub Track
Ovarian Cancer
Clinical Trial Registration Number
NCT02477644
Citation
J Clin Oncol 39, 2021 (suppl 15; abstr 5514)
DOI
10.1200/JCO.2021.39.15_suppl.5514
Abstract #
5514
Abstract Disclosures
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