Phase III PAOLA-1/ENGOT-ov25 trial: Olaparib plus bevacizumab (bev) as maintenance therapy in patients (pts) with newly diagnosed, advanced ovarian...

Date 28 September 2019
Event ESMO 2019 Congress
Session Presidential Symposium I
Topics Ovarian Cancer
Presenter Isabelle Ray-Coquard
Citation Annals of Oncology (2019) 30 (suppl_5): v851-v934. 10.1093/annonc/mdz394
Authors I.L. Ray-Coquard1, P. Pautier2, S. Pignata3, D. Pérol4, A. González-Martín5, P. Sevelda6, K. Fujiwara7, I.B. Vergote8, N. Colombo9, J. Mäenpää10, F. Selle11, J. Sehouli12, D. Lorusso13, E.M. Guerra Alia14, C. Lefeuvre-Plesse15, U. Canzler16, A. Lortholary17, F. Marmé18, E. Pujade-Lauraine19, P. Harter20
  • 1,, Centre Léon Bérard, Lyon and GINECO, , - ,/FR
  • 2,, Institut Gustave Roussy, Villejuif and GINECO, ,/FR
  • 3,, Istituto Nazionale Tumori, Naples and IRCCS, MITO, ,/IT
  • 4,, Centre Léon Bérard, Lyon and GINECO, ,/FR
  • 5,, MD Anderson Cancer Center Madrid, Madrid and GEICO, ,/ES
  • 6,, Krankenhaus Hietzing; Abteilung Gynäkologie, Vienna, and AGO Au, ,/AT
  • 7,, Saitama Medical University, Saitama and GOTIC, ,/JP
  • 8,, University Hospital Leuven, Leuven Cancer Institute, Leuven and BGOG, ,/BE
  • 9,, European Institute of Oncology, Milan and MANGO, ,/IT
  • 10,, Tampere University and University Hospital, Tampere and NSGO, ,/FI
  • 11,, Groupe Hospitalier Diaconesses Croix Saint-Simon, Paris and GINECO, ,/FR
  • 12,, Charité ‒ Universitätsmedizin Berlin (CVK), Berlin and AGO, ,/DE
  • 13,, Fondazione IRCCS Istituto Nazionale Tumori, Milan and MITO, ,/IT
  • 14,, Hospital Universitario Ramón y Cajal, Madrid and GEICO, ,/ES
  • 15,, Centre Eugène Marquis, Rennes and GINECO, ,/FR
  • 16,, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden and AGO, ,/DE
  • 17., Centre Catherine de Sienne Hopital privé du Confluent, Nantes and GINECO, ./FR
  • 18,, Universitätsklinikum Heidelberg, Heidelberg and AGO, ,/DE
  • 19,, ARCAGY Research, Paris and GINECO, ,/FR
  • 20,, Kliniken Essen Mitte, Essen and AGO, ,/DE

LBA2_PR: Phase III PAOLA-1/ENGOT-ov25 trial: Olaparib plus bevacizumab (bev) as maintenance therapy in patients (pts) with newly diagnosed, advanced ovarian cancer (OC) treated with platinum-based chemotherapy (PCh) plus bev, by Isabelle Ray-Coquard

 

Abstract

Background

PAOLA-1/ENGOT-ov25 (NCT02477644) is the first phase III trial to evaluate the efficacy and safety of a PARP inhibitor with bev as first-line (1L) maintenance therapy for advanced OC, regardless of BRCA1/2 mutation (BRCAm) status.

Methods

PAOLA-1 is a randomized, double-blind, international phase III trial. Eligible pts had newly diagnosed, FIGO stage III–IV, high-grade serous or endometrioid OC, fallopian tube or primary peritoneal cancer. Pts had received standard PCh plus bev and were in clinical complete or partial response. Pts were randomized (2:1) to olaparib tablets (300 mg bid for up to 24 months [m]) plus bev (15 mg/kg, d1, q3w, for 15 m including when combined with PCh) or placebo (pbo) plus bev, stratified by 1L treatment outcome and tumour BRCAm status. The primary endpoint was investigator-assessed progression-free survival in the intent-to-treat population (PFS; modified RECIST v1.1).

Results

537 pts were randomized to olaparib plus bev and 269 to pbo plus bev. Pt characteristics were well balanced. Median follow-up was 24.0 m in the olaparib arm and 22.7 m in the pbo arm. PFS was significantly increased in the olaparib arm. PFS2 is immature.Table:

LBA2_PR

Median, monthsHR (95% CI)
Olaparib armPlacebo armP value
PFS, investigator-assessed (59% maturity) (n = 806)22.116.60.59 (0.49–0.72)
P < 0.0001
PFS by tBRCAm status* tBRCAm (n = 237)37.2 18.921.7 16.00.31 (0.20–0.47)
Non-tBRCAm (n = 569)0.71 (0.58–0.88)
PFS by HRD status HRD-positive*(n = 387) HRD-positive, non-tBRCA*(n = 152) HRD-negative/unknown§ (n = 419)37.2 28.1 16.917.7 16.6 16.00.33 (0.25–0.45) 0.43 (0.28–0.66) 0.92 (0.72–1.17)
*

These were prespecified subgroup analyses. PFS by tBRCAm was analysed using the electronic case report form dataset and PFS by HRD status by the myChoice® HRD Plus assay dataset (Myriad Genetic Laboratories, Inc);

HRD score ≥42 including pts with a tBRCAm;

HRD score ≥42 excluding pts with a tBRCAm;

§

HRD score <42 or inconclusive, missing or failed test CI, confidence interval; HR, hazard ratio; HRD, homologous recombination deficiency; PFS2, time to second progression; tBRCAm, tumour BRCA1/2 mutation.

Conclusions

Addition of olaparib to bev maintenance therapy following 1L PCh plus bev led to a statistically significant and clinically meaningful PFS benefit in pts with advanced OC. The PFS benefit in pts with a tBRCAm and in HRD-positive pts was substantial.

Clinical trial identification

NCT02477644.

Editorial acknowledgement

Medical writing assistance was provided by Laura Smart, MChem, from Mudskipper Business, Ltd, funded by ARCAGY Research, AstraZeneca, and MSD.

Legal entity responsible for the study

ARCAGY Research.

Funding

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

Disclosure

I.L. Ray-Coquard: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy: Clovis Oncology; Honoraria (self), Advisory / Consultancy: Tesaro; Honoraria (self), Advisory / Consultancy: Pharma Mar; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Genmab; Advisory / Consultancy, Research grant / Funding (self): MSD; Advisory / Consultancy: Pfizer. P. Pautier: Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Tesaro; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Genentech; Research grant / Funding (institution): PharmaMar. S. Pignata: Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): MSD; Honoraria (self): Pfizer; Honoraria (self): Incyte; Honoraria (self): Novartis; Honoraria (self): PharmaMar; Honoraria (self): Clovis Oncology; Honoraria (self): Tesaro. D. Pérol: Honoraria (self), Travel / Accommodation / Expenses: Roche; Honoraria (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self): Eli-Lilly; Honoraria (self): Ipsen; Honoraria (self): Novartis; Honoraria (self): BMS. A. González-Martín: Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Pfizer; Advisory / Consultancy: ImmunoGen; Advisory / Consultancy: PharmaMar; Advisory / Consultancy: MSD; Advisory / Consultancy: Genmad. P. Sevelda: Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Amgen. K. Fujiwara: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Chugai Roche; Honoraria (self): Zeria; Honoraria (self): Taiho; Honoraria (self): Nihon Kayaku; Honoraria (self): Kyowahakko Kirin; Honoraria (self): Janssen; Honoraria (self): Daiichi Sankyo; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Kaken. I.B. Vergote: Advisory / Consultancy: Advaxis, Inc.; Advisory / Consultancy: Eisai, Inc.; Advisory / Consultancy: MSD, Belgium; Advisory / Consultancy: Roche NV; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Genmab; Advisory / Consultancy: F. Hoffman-La Roche Ltd; Advisory / Consultancy, Travel / Accommodation / Expenses: PharmaMar; Advisory / Consultancy: Millennium Pharma; Advisory / Consultancy, Travel / Accommodation / Expenses: Clovis Oncology; Advisory / Consultancy: AstraZeneca NV; Advisory / Consultancy, Travel / Accommodation / Expenses: Tesaro; Advisory / Consultancy: Oncoinvent AS; Advisory / Consultancy, Travel / Accommodation / Expenses: Immunogen Inc.; Advisory / Consultancy: Sotio; Research grant / Funding (institution): Oncoinvent AS; Research grant / Funding (self): Amgen; Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Research grant / Funding (self): Stichting Tegen Kanker; Travel / Accommodation / Expenses: Takeda Oncology; Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: BIOCAD. N. Colombo: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: PharmaMar; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Tesaro; Honoraria (self), Advisory / Consultancy: Clovis Oncology; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: BIOCAD; Honoraria (self), Advisory / Consultancy: Takeda. J. Mäenpää: Honoraria (self), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Tesaro; Advisory / Consultancy: Glovis. F. Selle: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Travel / Accommodation / Expenses: MSD France; Honoraria (self): PharmaMar; Honoraria (self), Travel / Accommodation / Expenses: Tesaro; Honoraria (self): Clovis Oncology; Honoraria (self), Travel / Accommodation / Expenses: AstraZeneca; Non-remunerated activity/ies: Post-university teaching. J. Sehouli: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Clovis Oncology; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Tesaro; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Roche Diagnostics; Advisory / Consultancy: Merck; Advisory / Consultancy: Bayer; Advisory / Consultancy: Eisei; Advisory / Consultancy: Johnson & Johnson; Advisory / Consultancy: MSD; Advisory / Consultancy: Novocure; Advisory / Consultancy: Amgen; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Bristol-Myers Squibb. D. Lorusso: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Tesaro; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Clovis Oncology; Advisory / Consultancy: Immunogen; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Officer / Board of Directors: GCIG. E.M. Guerra Alia: Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: AstraZeneca; Speaker Bureau / Expert testimony: V Simposio Grupo Español de Investigación en Cáncer de Ovario (GEICO); Travel / Accommodation / Expenses: Baxter; Speaker Bureau / Expert testimony: Sociedad Española de Nutrición (SENPE)Parenteral y Enteral. C. Lefeuvre-Plesse: Advisory / Consultancy: AstraZeneca; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: Pfizer. U. Canzler: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Lilly. A. Lortholary: Honoraria (self): AstraZeneca; Honoraria (self): Tesaro. F. Marmé: Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self): Tesaro; Honoraria (self): Clovis Oncology; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self): Celgene; Honoraria (self): Genomic Health; Honoraria (self), Advisory / Consultancy: PharmaMar; Honoraria (self): Amgen; Advisory / Consultancy: Curvac Celgene; Advisory / Consultancy: Curevac; Advisory / Consultancy: Vaccibody. E. Pujade-Lauraine: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Tesaro; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Clovis Oncology; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Tesaro; Advisory / Consultancy: Genmab; Advisory / Consultancy: Incyte; Advisory / Consultancy: MSD; Advisory / Consultancy: Pfizer. P. Harter: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Sotio; Honoraria (self), Advisory / Consultancy: Tesaro; Honoraria (self): Stryker; Honoraria (self): ASCO; Honoraria (self): Zai Lab; Honoraria (self): MSD; Advisory / Consultancy: Lilly; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Immunogen; Advisory / Consultancy: MSD/Merck.