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Mini Oral - Gynaecological cancers 1

LBA33 - Maintenance olaparib plus bevacizumab (bev) in patients (pts) with newly diagnosed advanced high‐grade ovarian carcinoma (HGOC): Final analysis of second progression-free survival (PFS2) in the phase III PAOLA-1/ENGOT-ov25 trial

Date

18 Sep 2020

Session

Mini Oral - Gynaecological cancers 1

Presenters

Antonio González Martín

Citation

Annals of Oncology (2020) 31 (suppl_4): S1142-S1215. 10.1016/annonc/annonc325

Authors

A. González Martín1, Y. Tazi2, F. Heitz3, L. Montane4, P. Gargiulo5, R. Berger6, K. Yonemori7, I. Vergote8, A. Bologna9, J. Maenpaa10, C. Costan11, U. Canzler12, C. Zamagni13, E.M. Guerra-Alia14, C.B. Levaché15, F. Marmé16, E. Kalbacher17, N. De Gregorio18, N. Dohollou19, I.L. Ray-Coquard20

Author affiliations

  • 1 Medical Oncology Department, Clinica Universidad de Navarra and GEICO, 28027 - Madrid/ES
  • 2 -, Strasbourg Oncologie Libérale and GINECO, Paris/FR
  • 3 Department For Gynecology And Gynecologic Oncology, Kliniken Essen-Mitte and AGO, Essen/DE
  • 4 -, Centre Léon Bérard, Lyon/FR
  • 5 Clinical Trial Unit, Istituto Nazionale Tumori, IRCCS, Fondazione G. Pascale, and MITO, 80131 - Napoli/IT
  • 6 Medical Oncology, Medical University Innsbruck, Univ. Clinic for Gynaecology and Obstetrics, and AGO-Austria, 6020 - Innsbruck/AT
  • 7 Breast And Medical Oncology, National Cancer Center, and GOTIC, 104-0045 - Tokyo/JP
  • 8 Department Of Gynecology, University Hospital Leuven, Leuven Cancer Institute, and BGOG, Leuven/BE
  • 9 -, Azienda Unità Sanitaria Locale di Reggio Emilia, IRCCS, and MANGO, Reggio Emilia/IT
  • 10 -, Tampere University and University Hospital, and NSGO, 33521 - Tampere/FI
  • 11 -, Hôpital Michallon, Centre Hospitalier Universitaire de Grenoble, and GINECO, Grenoble/FR
  • 12 -, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, and AGO, Dresden/DE
  • 13 S.s.d. Oncologia Medica Addarii, Policlinico S.Orsola-Malpighi, and MITO, 40138 - Bologna/IT
  • 14 -, Hospital Universitario Ramón y Cajal, and GEICO, Madrid/ES
  • 15 -, Polyclinique Francheville, and GINECO, Périgueux/FR
  • 16 Gynecologic Oncology Department, Universitätsklinikum Heidelberg, and AGO, Heidelberg/DE
  • 17 Oncology Department, CHRU de Besançon, Hôpital Jean Minjoz, and GINECO, 25030 - Besançon/FR
  • 18 -, Universitätsklinikum Ulm, and AGO, 89081 - Ulm/DE
  • 19 -, Polyclinique Bordeaux Nord Aquitaine, and GINECO, 33077 - Bordeaux/FR
  • 20 Medical Oncology Department, Centre Léon Bérard and University Claude Bernard Lyon I, GINECO group France, 69008 - Lyon/FR
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Abstract LBA33

Background

In the primary analysis of PAOLA-1/ENGOT-ov25 (NCT02477644), adding olaparib to maintenance bev after first-line platinum-based chemotherapy with bev led to a significant progression-free survival benefit in advanced HGOC pts (HR 0.59; 95% CI 0.49 -0.72) (Ray-Coquard et al. NEJM 2019); PFS2 was immature. Here, we report final PFS2 data from PAOLA-1.

Methods

Pts with newly diagnosed, FIGO stage III -IV HGOC in response after platinum-based chemotherapy plus bev randomized to olaparib tablets (300 mg bid for 24 months) + bev (15 mg/kg q3w for 15 months) or placebo + bev. PFS2 and time to second subsequent therapy or death (TSST) were key secondary endpoints (final PFS2 analysis planned for ≈53% data maturity or 1 year after primary analysis).

Results

537 pts were randomized to olaparib + bev and 269 to placebo + bev with median PFS2 follow-up of 35.5 and 36.5 months, respectively (data cut-off 22 March 2020). Olaparib + bev provided a statistically significant reduction in the risk of second progression or death vs placebo + bev (ITT analysis; HR 0.78; 95% CI 0.64 -0.95; P=0.0125) (Table). HRs for PFS2 by biomarker status with olaparib + bev vs placebo + bev were 0.53 in pts with a tumour BRCA mutation (tBRCAm), 0.56 in HRD-positive pts, 0.60 in HRD-positive pts without a tBRCAm and 1.04 in HRD-negative pts. TSST was longer with olaparib + bev vs placebo + bev (median 38.2 vs 31.5 months) (HR 0.78; 95% CI 0.64 -0.95; P=0.0115). 49/537 (9%) olaparib + bev pts and 72/269 (27%) placebo + bev pts received a PARP inhibitor as first subsequent therapy. No new safety signals were seen with longer follow-up. Table: LBA33

PFS2 No. of events/no. of pts (%) Median, months HR (95% CI); P-value
Olaparib + bev Placebo + bev Olaparib + bev Placebo + bev
ITT 260/537 (48) 164/269 (61) 36.5 32.6 0.78 (0.64–0.95); P=0.0125
tBRCAm 41/157 (26) 36/80 (45) NR 45.0 0.53 (0.34–0.83)
HRD positive* 85/255 (33) 70/132 (53) 50.3 35.3 0.56 (0.41–0.77)
HRD positive excluding tBRCAm 41/97 (42) 33/55 (60) 50.3 30.1 0.60 (0.38–0.96)
HRD negative 127/192 (66) 61/85 (72) 24.4 26.4 1.04 (0.77–1.42)
HRD unknown 48/90 (53) 33/52 (63) 34.0 30.1 0.85 (0.55–1.33)

*tBRCAm and/or genomic instability. Unstable due to lack of events. CI, confidence interval; ITT, intent to treat; HR, hazard ratio; HRD, homologous recombination deficiency; NR, not reached

Conclusions

Adding maintenance olaparib to bev provided a benefit beyond first progression, with a substantial PFS2 benefit in tBRCAm and HRD-positive pts. The statistically significant improvement in PFS2 seen with olaparib + bev vs placebo + bev was supported by a similar TSST benefit.

Clinical trial identification

NCT02477644.

Editorial acknowledgement

Medical writing assistance was provided by Gillian Keating, MBChB, from Mudskipper Business Limited.

Legal entity responsible for the study

ARCAGY Research.

Funding

ARCAGY Research, AstraZeneca, Merck & Co., and F. Hoffmann-La Roche.

Disclosure

A. González Martín: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Tesaro; Advisory/Consultancy: Clovis; Advisory/Consultancy: Pfizer/Merck; Advisory/Consultancy: ImmunoGen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pharmamar; Advisory/Consultancy: MSD; Advisory/Consultancy: Genmab; Advisory/Consultancy: Oncoinvent; Non-remunerated activity/ies, Principal investigator of PRIMA study: Tesaro; Leadership role, Chairman GEICO (Grupo Español Investigación Cáncer de Ovario): GEICO; Leadership role, Chairman ENGOT (European Network for Gynecological Oncologic Trials): ENGOT; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Tesaro/GSK; Advisory/Consultancy: Amgen; Advisory/Consultancy: Genmab; Advisory/Consultancy: Oncoinvent; Advisory/Consultancy: Novartis. F. Heitz: Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Tesaro; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self): Clovis. R. Berger: Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Merck; Travel/Accommodation/Expenses: Biocad; Travel/Accommodation/Expenses: Clovis; Travel/Accommodation/Expenses: Advaxis; Honoraria (self): AstraZeneca; Advisory/Consultancy: PharmaMar. K. Yonemori: Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): Taiho; Honoraria (self), Advisory/Consultancy: Eisai; Advisory/Consultancy: Takeda; Advisory/Consultancy: Novartis; Advisory/Consultancy: Ono. I. Vergote: Honoraria (institution): Advaxis; Honoraria (institution): Eisai; Honoraria (institution): MSD Belgium; Honoraria (institution): F. Hoffman-La Roche; Honoraria (institution): Millennium Pharmaceuticals; Honoraria (institution), Research grant/Funding (self): Oncoinvent; Honoraria (institution): Sotio; Honoraria (institution), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (institution), Research grant/Funding (self), Travel/Accommodation/Expenses: Genmab; Honoraria (institution), Travel/Accommodation/Expenses: PharmaMar; Honoraria (institution), Travel/Accommodation/Expenses: Clovis Oncology; Honoraria (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (institution), Travel/Accommodation/Expenses: Immunogen; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Stichting tegen Kanker. J. Maenpaa: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Clovis; Advisory/Consultancy: MSD; Advisory/Consultancy: Orion Pharma; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Tesaro/GSK. C. Costan: Advisory/Consultancy: AstraZeneca. U. Canzler: Honoraria (self): AstraZeneca; Honoraria (self): Roche; Honoraria (self): Lilly. C. Zamagni: Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Tesaro; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: PharmaMar; Advisory/Consultancy, Travel/Accommodation/Expenses: Celgene; Research grant/Funding (self), Travel/Accommodation/Expenses: Pierre Fabre; Research grant/Funding (self), Travel/Accommodation/Expenses: Istituto Gentilli; Advisory/Consultancy: Eisai; Advisory/Consultancy: Lilly; Advisory/Consultancy: Amgen; Advisory/Consultancy: QuintilesIMS; Research grant/Funding (self): Takeda; Research grant/Funding (self): Teva; Research grant/Funding (self): Medivation; Research grant/Funding (self): AbbVie; Research grant/Funding (self): Array BioPharma; Research grant/Funding (self): Morphotek; Research grant/Funding (self): Synthon; Research grant/Funding (self): Seattle Genetics. E.M. Guerra-Alia: Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Clovis; Advisory/Consultancy: Tesaro; Advisory/Consultancy: PharmaMar; Advisory/Consultancy: AstraZeneca; Travel/Accommodation/Expenses: Baxter. C.B. Levaché: Honoraria (institution): Genomic Health; Honoraria (institution): Novartis; Honoraria (institution): Pfizer; Honoraria (institution): Roche. F. Marmé: Honoraria (institution), Advisory/Consultancy: AstraZeneca; Honoraria (institution), Advisory/Consultancy: Roche; Honoraria (institution), Advisory/Consultancy: Clovis; Honoraria (institution), Advisory/Consultancy: Pfizer; Honoraria (institution), Advisory/Consultancy: Tesaro; Honoraria (institution), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: EIASI; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: PharmaMar; Honoraria (self), Advisory/Consultancy: Genomic Health; Honoraria (self), Advisory/Consultancy: Celgene; Advisory/Consultancy: CureVac; Advisory/Consultancy: Janssen-Cilag; Advisory/Consultancy, Paid to institution: Immunomedics. E. Kalbacher: Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi; Advisory/Consultancy, Travel/Accommodation/Expenses: Tesaro; Advisory/Consultancy, Travel/Accommodation/Expenses: GSK; Advisory/Consultancy, Travel/Accommodation/Expenses: Leopharma. N. De Gregorio: Advisory/Consultancy: Roche; Advisory/Consultancy: PharmaMar; Advisory/Consultancy: Amgen; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: GSK. N. Dohollou: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Roche; Advisory/Consultancy: Lilly; Research grant/Funding (institution), serving as PI of a clinical trial: BMS; Research grant/Funding (institution), serving as PI of a clinical trial: Boehringer Ingelheim; Research grant/Funding (institution), serving as PI of a clinical trial: Genomic Health; Research grant/Funding (institution), serving as PI of a clinical trial: MSD; Research grant/Funding (institution), serving as PI of a clinical trial: Novartis. I.L. Ray-Coquard: Honoraria (self), Advisory/Consultancy: Abbvie; Honoraria (self), Advisory/Consultancy: Agenus; Honoraria (self), Advisory/Consultancy: Advaxis; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): BMS; Honoraria (self), Advisory/Consultancy: PharmaMar; Honoraria (self), Advisory/Consultancy: Genmab; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Honoraria (institution), Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: GSK; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): MSD; Honoraria (self), Advisory/Consultancy: Deciphera; Honoraria (self), Advisory/Consultancy: Mersena; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck Sereno; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: Tesaro; Honoraria (self), Advisory/Consultancy: Clovis; Advisory/Consultancy: Roche/Genentech. All other authors have declared no conflicts of interest.

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