5029 - POLO: Time to treatment discontinuation and subsequent therapies following maintenance olaparib for patients (pts) with a germline BRCA mutation and metastatic pancreatic cancer (mPC)

Background

In the randomized Phase III POLO trial (NCT02184195), progression-free survival (PFS) for pts with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) and mPC was significantly prolonged with maintenance olaparib versus placebo. Maintenance treatment has the potential to prolong time without subsequent chemotherapies and their associated toxicities.

Methods

Eligible pts had a gBRCAm and mPC that had not progressed following ≥16 weeks of first-line platinum-based chemotherapy. Pts were randomized to receive maintenance olaparib tablets (300 mg bid) or placebo until investigator-assessed progression or unacceptable toxicity. Time from randomization to discontinuation of treatment (TDT), and initiation of first (TFST) and second (TSST) subsequent therapies following discontinuation of study treatment or death, were secondary endpoints, analysed by log-rank test. Follow-up for subsequent therapies took place 30 days after discontinuation, then every 8 weeks.

Results

92 and 62 pts were randomized to olaparib and placebo, respectively. TDT, TFST and TSST were meaningfully longer in the olaparib arm (Table). 30 olaparib (32.6%) and 8 placebo arm (12.9%) pts were on study treatment at the data cut-off. 54 (58.7%) and 49 (79.0%) pts, respectively, had discontinued treatment due to progression; 4 (4.3%) and 2 (3.2%), respectively, due to an adverse event. 45 olaparib (48.9%) and 46 placebo arm (74.2%) pts received subsequent treatment; all received chemotherapy in the second line, except for two placebo arm pts who received olaparib.Table:

693P

Conclusions

Pts with a gBRCAm and mPC received maintenance olaparib for meaningfully longer than placebo. Initiation of subsequent second-line treatment, typically cytotoxic chemotherapy, was delayed for pts in the olaparib arm and data suggest this effect may be maintained through to subsequent third-line therapy.

Clinical trial identification

NCT02184195.

Editorial acknowledgement

Elin Pyke, MChem, from Mudskipper Business, Ltd, funded by AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, U.S.A. (MSD).

Legal entity responsible for the study

AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, U.S.A. (MSD).

Funding

AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, U.S.A. (MSD).

Disclosure

E. Van Cutsem: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy, Research grant / Funding (institution): Merck Sharpe & Dohme; Advisory / Consultancy, Research grant / Funding (institution): Merck KGaA; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Servier; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Ipsen. T. Golan: Honoraria (self), Research grant / Funding (institution), International coordinating investigator service fee: AstraZeneca; Research grant / Funding (institution): MSD Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony, Personal fee for advisory board and speakers bureau: AbbVie; Advisory / Consultancy, Personal fees for consultancy: Teva. P. Hammel: Research grant / Funding (institution): Celgene; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution), Travel / Accommodation / Expenses: Erythec; Honoraria (self), Research grant / Funding (institution): Halozyme. M. Reni: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses, Non-remunerated activity/ies: Celgene; Honoraria (self), Advisory / Consultancy: Baxalta; Honoraria (self), Advisory / Consultancy: Shire; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novocure; Advisory / Consultancy: Novartis; Non-remunerated activity/ies: Boston Pharmaceutics; Non-remunerated activity/ies: AstraZeneca. T. Macarulla: Advisory / Consultancy: Genzyme, Sanofi/Aventis, Shire, Tesaro, Baxalta, QED Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Advisory / Consultancy, Research grant / Funding (institution): Roche; Research grant / Funding (institution): Agios Pharmaceuticals Inc; Research grant / Funding (institution): Aslan Pharmaceuticals Pte Ltd; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Halozyme Inc; Research grant / Funding (institution): Immunomedics; Research grant / Funding (institution): Lilly, S.A.; Research grant / Funding (institution): Merrimack; Research grant / Funding (institution): Millennium; Research grant / Funding (institution): Novartis Farmaceutica, S.A.; Research grant / Funding (institution): Novocure GmBH, Oncomed, Pfizer, S.L.U., Pharmacyclics; Travel / Accommodation / Expenses: Merck, H3 Biomedicine, Bayer, Sanofi. M.J. Hall: Non-remunerated activity/ies, Collaborative research only in which company data was shared and assessed and research published—no funding or payment: Myriad; Non-remunerated activity/ies, Collaborative research only in which company data was shared and assessed and research published—no funding or payment: Ambry; Non-remunerated activity/ies, Collaborative research only in which company data was shared and assessed and research published—no funding or payment: Invitae; Non-remunerated activity/ies, Collaborative research only in which company data was shared and assessed and research published—no funding or payment: Foundation Medicine; Travel / Accommodation / Expenses, Non-remunerated activity/ies, Collaborative research only in which company data was shared and assessed and research published—no funding or payment. Travel/accomodation/expenses as part of research collaboration Precision Oncology Alliance: Caris Lifesciences; Research grant / Funding (institution), Non-remunerated activity/ies, Keynote 177 trial site PI: Merck; Research grant / Funding (institution), Travel / Accommodation / Expenses, Non-remunerated activity/ies, As part of clinical trial leadership and steering committee; POLO trial site PI: AstraZeneca. J.O. Park: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Celgene; Honoraria (self), Advisory / Consultancy: Shire; Advisory / Consultancy: Merck Serono. D. Arnold: Advisory / Consultancy: Lilly. D. Oh: Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Advisory / Consultancy, Research grant / Funding (self): Novartis; Research grant / Funding (self): Array; Research grant / Funding (self): Eli Lilly; Research grant / Funding (self): Green Cross; Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Bayer; Advisory / Consultancy: Taiho; Advisory / Consultancy: ASLAN. A. Reinacher-Schick: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy: Baxalta; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Honoraria (self), Research grant / Funding (institution): Ipsen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Lilly; Honoraria (self), Advisory / Consultancy: Merck Serono; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy: Sanofi-Aventis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Servier; Honoraria (self): Shire; Research grant / Funding (institution): AstraZeneca. G. Tortora: Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy: Incyte; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis. H. Algül: Honoraria (self), Travel / Accommodation / Expenses: Celgene; Honoraria (self): Servier; Research grant / Funding (self): Chugai. E.M. O’Reilly: Advisory / Consultancy, Eileen M O’Reilly and spouse: 3DMedcare, Alignmed, Amgen, Antengene, Aptus, Aslan, Astellas, Bioline, Boston Scientific, Bridgebio, Carsgen, Cipla, CytomX, Daiichi, Debio, Delcath, Eisai, Genoscience, Hengrui, Inovio, Ipsen, Jazz, Jansen, Kyowa Kirin, LAM, Loxo, Merck, Mina, Novella,; Advisory / Consultancy, Research grant / Funding (institution), Eileen M O’Reilly and spouse: Agios, AstraZeneca, Bayer, Beigene, BMS, Casi, Celgene, Exelixis, Halozyme, Incyte, Lilly, QED; Research grant / Funding (institution), Eileen M O’Reilly and spouse: ActaBiologica, Array, Genentech, Mabvax, Novartis, Oncoquest, Polaris Puma, Roche; Advisory / Consultancy, Eileen M O’Reilly and spouse: Onxeo, PCI Biotech, Pfizer, Pieris, QED, Redhill, Sanofi, Servier, Silenseed, Sillajen, Sobi, Targovax, Tekmira, Twoxar, Vicus, Yakult, Yiviva. D. McGuinness: Full / Part-time employment, Contractor: AstraZeneca. K.Y. Cui: Full / Part-time employment: AstraZeneca; Research grant / Funding (institution), AstraZeneca receives payment from Merck to codevelop olaparib: Merck & Co. Inc. K. Schlienger: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: MSD. G.Y. Locker: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. H.L. Kindler: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Advisory / Consultancy: Aldeyra Therapeutics; Advisory / Consultancy: Astellas; Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer-Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Erytech; Advisory / Consultancy: Five Prime Therapeutics; Advisory / Consultancy: Ipsen Pharmaceuticals; Advisory / Consultancy: Kyowa; Advisory / Consultancy, Travel / Accommodation / Expenses: Paredox Therapeutics; Research grant / Funding (institution): Aduro; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Dicephera; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Polaris; Research grant / Funding (institution): Verastem. All other authors have declared no conflicts of interest.