1468P - POLO: Subsequent therapy after maintenance olaparib in patients with a germline BRCA mutation and metastatic pancreatic cancer

Background

In the phase III POLO trial (NCT02184195), progression-free survival was significantly prolonged on maintenance olaparib (O) relative to placebo (P) in patients (pts) with a germline BRCA mutation and metastatic pancreatic cancer whose disease had not progressed after ≥ 16 weeks of first-line platinum-based chemotherapy. Here, we present subsequent therapies received after discontinuation of study treatment.

Methods

A total of 154 pts were randomized 3:2 to receive maintenance O (300 mg tablets b.i.d.; n = 92) or P (n = 62). Treatment was continued until disease progression (blinded independent central review) or unacceptable toxicity. After treatment discontinuation, subsequent therapies were administered at the discretion of the investigators. Subsequent therapy response rates (complete or partial) were assessed by investigator.

Results

At data cut-off (21 July 2020), median duration of follow-up was 31.3 months in the O arm and 23.9 months in the P arm, and 77 pts (83.7%) and 59 pts (95.2%), respectively, had discontinued study treatment. Of pts who had discontinued treatment, 56 (72.7%) in the O arm and 54 (91.5%) in the P arm had received a second-line therapy; the proportion of pts who received a subsequent platinum-based chemotherapy and/or a PARP inhibitor was greater in the P arm than in the O arm (Table). The most common subsequent therapies were platinum-based chemotherapies, most commonly FOLFIRINOX. Among pts who had received second-line therapy, the response rate was 5.3% in the O arm and 5.6% in the P arm, while 28.1% and 24.1% of pts, respectively, had stable disease. Table: 1468P

Subsequent therapies after maintenance treatment discontinuation

^aExcluding PARPi; ^bOne patient received both PARPi and platinum PARPi, poly(ADP ribose) polymerase inhibitor

Conclusions

The majority of pts in POLO who discontinued study treatment received at least one subsequent therapy. Exposure to subsequent therapy was lower among pts in the O arm than among pts in the P arm. No differences in response rates to second-line therapy were observed.

Clinical trial identification

NCT02184195 Release date: 6 June 2014.

Editorial acknowledgement

Stephen Sweet, PhD, and Luisana Carballo, of Oxford PharmaGenesis, Oxford, UK, provided medical writing assistance.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca, as part of an alliance with and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

T. Golan: Financial Interests, Personal, Advisory Role: AbbVie; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Teva; Financial Interests, Personal, Speaker’s Bureau: AbbVie; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Other, Travel, accommodations, expenses: AstraZeneca; Financial Interests, Personal, Other, Travel, accommodations, expenses: MSD; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: MSD; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Other, Honoraria: Rafael Pharmaceuticals. P. Hammel: Financial Interests, Personal, Advisory Role: Vect-Horus; Financial Interests, Personal, Advisory Role: Halozyme; Financial Interests, Personal, Advisory Role: ERYTECH Pharma; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Mylan; Financial Interests, Personal, Speaker’s Bureau: ERYTECH Pharma; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Servier; Financial Interests, Personal, Other, Travel, accommodations, expenses: Halozyme; Financial Interests, Personal, Other, Travel, accommodations, expenses: Pfizer; Financial Interests, Personal, Other, Travel, accommodations, expenses: Vect-Horus; Financial Interests, Institutional, Funding: ERYTECH Pharma; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Halozyme; Financial Interests, Personal, Other: BMS; Non-Financial Interests, Personal, Other: Ipsen; Non-Financial Interests, Personal, Other: Novartis. M. Reni: Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Advisory Role: Baxalta/Shire; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Baxter; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Servier; Financial Interests, Personal, Other, Travel, accommodations, expenses: Celgene; Financial Interests, Personal, Other: Celgene; Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Funding: Celgene. E. Van Cutsem: Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: SERVIER; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Role: Merck KGaA; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Halozyme; Financial Interests, Personal, Advisory Role: Array BioPharma; Financial Interests, Personal, Advisory Role: Biocartis; Financial Interests, Personal, Advisory Role: GlaxoSmithKline; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Personal, Advisory Role: Sirtex Medical; Financial Interests, Personal, Advisory Role: Taiho Pharmaceutical; Financial Interests, Personal, Advisory Role: Incyte; Financial Interests, Institutional, Funding: amgen; Financial Interests, Institutional, Funding: Bayer; Financial Interests, Institutional, Funding: Boehringer Ingelheim; Financial Interests, Institutional, Funding: Lilly; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Funding: Celgene; Financial Interests, Institutional, Funding: Ipsen; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: Merck KGaA; Financial Interests, Institutional, Funding: SERVIER; Financial Interests, Institutional, Funding: Bristol-Myers Squibb. T. Macarulla Mercade: Financial Interests, Personal, Advisory Role: Sanofi/Aventis; Financial Interests, Personal, Advisory Role: Shire; Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Baxalta; Financial Interests, Personal, Advisory Role: QED Therapeutics; Financial Interests, Personal, Advisory Role: Baxter; Financial Interests, Personal, Advisory Role: Incyte; Financial Interests, Personal, Advisory Role: SERVIER; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Other, Travel, accommodations, expenses: Merck; Financial Interests, Personal, Other, Travel, accommodations, expenses: H3 Biomedicine; Financial Interests, Personal, Other, Travel, accommodations, expenses: Sanofi; Financial Interests, Personal, Other, Travel, accommodations, expenses: Celgene; Financial Interests, Personal, Other, Travel, accommodations, expenses: SERVIER; Financial Interests, Institutional, Funding: Celgene; Financial Interests, Institutional, Funding: Agios; Financial Interests, Institutional, Funding: ASLAN Pharmaceuticals; Financial Interests, Institutional, Funding: Bayer; Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Funding: Genentech; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Halozyme; Financial Interests, Institutional, Funding: Immunomedics; Financial Interests, Institutional, Funding: Lilly; Financial Interests, Institutional, Funding: Merrimack; Financial Interests, Institutional, Funding: Millennium; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Novocure; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: Pharmacyclics. M.J. Hall: Financial Interests, Personal, Other, Travel, accommodations, expenses: Foundation Medicine; Financial Interests, Personal, Other, Travel, accommodations, expenses: Caris Life Sciences; Financial Interests, Personal, Other, Travel, accommodations, expenses: Myriad Genetics; Financial Interests, Personal, Other, Travel, accommodations, expenses: AstraZeneca; Financial Interests, Institutional, Royalties, I share a patent with several Fox Chase investigators for a novel method to investigate hereditary CRC genes: Fox Chase investigators; Financial Interests, Personal, Other: Myriad Genetics; Financial Interests, Personal, Other: Foundation Medicine; Financial Interests, Personal, Other: Invitae; Financial Interests, Personal, Other: Caris Life Sciences; Financial Interests, Personal, Funding: InVitae; Financial Interests, Personal, Funding: Foundation Medicine; Financial Interests, Personal, Funding: Caris Life Sciences; Financial Interests, Personal, Funding: Myriad Genetics; Financial Interests, Personal, Funding: AstraZeneca; Financial Interests, Personal, Funding: Ambry Genetics. J.O. Park: Financial Interests, Institutional, Funding: Celgene; Financial Interests, Institutional, Funding: MedPactor; Financial Interests, Institutional, Funding: Servier. D. Hochhauser: Financial Interests, Personal, Speaker’s Bureau: Pierre Fabre; Financial Interests, Personal, Other, Travel, accommodations, expenses: Celgene; Financial Interests, Personal, Stocks/Shares: Roche; Financial Interests, Personal, Stocks/Shares: Novartis; Financial Interests, Personal, Funding: Merck Serono. D. Arnold: Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Merck Serono; Financial Interests, Personal, Advisory Role: Servier; Financial Interests, Personal, Advisory Role: Biocompatibles; Financial Interests, Personal, Advisory Role: Terumo; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: MSD Oncology; Financial Interests, Personal, Advisory Role: CME Provider AstraZeneca; Financial Interests, Personal, Advisory Role: CME Provider CRA International; Financial Interests, Personal, Advisory Role: CME Provider Hexal; Financial Interests, Personal, Advisory Role: IQVIA; Financial Interests, Personal, Advisory Role: Consulting Ketchum; Financial Interests, Personal, Advisory Role: Merck, Sharp and Dome; Financial Interests, Personal, Advisory Role: Pierre Fabre Pharma; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Samsung Bioepsis; Financial Interests, Personal, Advisory Role: Sanofi (Genzyme); Financial Interests, Personal, Advisory Role: CME Provider Terumo; Financial Interests, Personal, Invited Speaker: ACE Oncology; Financial Interests, Personal, Invited Speaker: CME Provider Amgen; Financial Interests, Personal, Invited Speaker: Aptitude Health; Financial Interests, Personal, Invited Speaker: CME Provider art tempi media; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Boston Scientific; Financial Interests, Personal, Invited Speaker: Bristol Meyer Squibb; Financial Interests, Personal, Invited Speaker: Clinical Care Options (CCO); Financial Interests, Personal, Invited Speaker: Consulting Agency Eli Lilly; Financial Interests, Personal, Invited Speaker: From Research to Practice; Financial Interests, Personal, Invited Speaker: Imedex; Financial Interests, Personal, Invited Speaker: CME Provider Ipsen; Financial Interests, Personal, Invited Speaker: Consulting Agency MedAhead (Austria); Financial Interests, Personal, Invited Speaker: CME Provider Merck (Serono); Financial Interests, Personal, Invited Speaker: Merck, Sharp and Dome; Financial Interests, Personal, Invited Speaker: PharmaCept; Financial Interests, Personal, Invited Speaker: Pierre Fabre Pharma; Financial Interests, Personal, Invited Speaker: PRMA Consulting; Financial Interests, Personal, Invited Speaker: CME Provider Roche; Financial Interests, Personal, Invited Speaker: Samsung Bioepsis; Financial Interests, Personal, Invited Speaker: Sanofi (Genzyme); Financial Interests, Personal, Invited Speaker: Servier; Financial Interests, Personal, Invited Speaker: streamitup Germany; Financial Interests, Personal, Invited Speaker: CME Provider Tactics MD LLC; Financial Interests, Personal, Invited Speaker: Terumo; Financial Interests, Personal, Invited Speaker: WebMD Health Corp; Financial Interests, Personal, Other: CME Provider Elsevier; Financial Interests, Personal, Other, Associate Editor: ESMO Open and Ann Oncol Elsevier; Financial Interests, Personal, Other, Associate Editor: Clin Colorect Cancer Oxford Universal Press; Financial Interests, Institutional, Other: Sanofi (Genzyme); Non-Financial Interests, Institutional, Other, Local PI, Associate Editor: Ann Oncol Bristol Meyer Squibb; Non-Financial Interests, Institutional, Other, Local PI: Pierre Fabre Pharma; Non-Financial Interests, Institutional, Other, Coordinating PI: OncoLytics; Non-Financial Interests, Institutional, Other, Steering Committee Member: Roche. D. Oh: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Genentech/Roche; Financial Interests, Personal, Advisory Role: Merck Serono; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Taiho Pharmaceutical; Financial Interests, Personal, Advisory Role: ASLAN Pharmaceuticals; Financial Interests, Personal, Advisory Role: Halozyme; Financial Interests, Personal, Advisory Role: Zymeworks; Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Advisory Role: BeiGene; Financial Interests, Personal, Advisory Role: Basilea; Financial Interests, Personal, Advisory Role: Turning Point; Financial Interests, Personal, Funding: AstraZeneca; Financial Interests, Personal, Funding: Novartis; Financial Interests, Personal, Funding: Array BioPharma; Financial Interests, Personal, Funding: Lilly; Financial Interests, Personal, Funding: Servier; Financial Interests, Personal, Funding: BeiGene; Financial Interests, Personal, Funding: MSD; Financial Interests, Personal, Funding: Handok. A. Reinacher-Schick: Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Sanofi/Aventis; Financial Interests, Personal, Advisory Role: Merck Serono; Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Servier; Financial Interests, Personal, Advisory Role: Baxalta; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Onkowissen; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Personal, Other, Travel, accommodations, expenses: Ipsen; Financial Interests, Personal, Other, Travel, accommodations, expenses: Amgen; Financial Interests, Personal, Other, Travel, accommodations, expenses: Celgene; Financial Interests, Personal, Other, Travel, accommodations, expenses: Onkowissen; Financial Interests, Personal, Other, Travel, accommodations, expenses: Roche; Financial Interests, Personal, Other, Travel, accommodations, expenses: Servier; Financial Interests, Personal, Other, Travel, accommodations, expenses: MCI Group; Financial Interests, Personal, Other, Travel, accommodations, expenses: Pierre Fabre; Financial Interests, Personal, Other, Travel, accommodations, expenses: AstraZeneca; Financial Interests, Personal, Other, Travel, accommodations, expenses: Merck Serono; Financial Interests, Personal, Other, Travel, accommodations, expenses: MSD; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Sanofi/Aventis; Financial Interests, Personal, Other, Honoraria: Merck Serono; Financial Interests, Personal, Other, Honoraria: Shire; Financial Interests, Personal, Other, Honoraria: Celgene; Financial Interests, Personal, Other, Honoraria: Lilly; Financial Interests, Personal, Other, Honoraria: Bristol-Myers Squibb; Financial Interests, Personal, Other, Honoraria: Servier; Financial Interests, Personal, Other, Honoraria: Baxalta; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Other, Honoraria: Aurikamed; Financial Interests, Personal, Other, Honoraria: BOVita; Financial Interests, Personal, Other, Honoraria: iomedico; Financial Interests, Personal, Other, Honoraria: med publico; Financial Interests, Personal, Other, Honoraria: promedicis; Financial Interests, Personal, Other, Honoraria: MCI Group; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Funding: Celgene; Financial Interests, Institutional, Funding: Ipsen; Financial Interests, Institutional, Funding: Amgen; Financial Interests, Institutional, Funding: Alexion Pharmaceuticals; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Lilly; Financial Interests, Institutional, Funding: Servier; Financial Interests, Institutional, Funding: AIO-Studien; Financial Interests, Institutional, Funding: Georgius Agricola Stiftung Ruhr; Financial Interests, Institutional, Funding: MOLOGEN; Financial Interests, Institutional, Funding: Ludwig Maximilian University of Munich; Financial Interests, Institutional, Funding: University of Erlangen-Nuremberg; Financial Interests, Institutional, Funding: University of Cologne; Financial Interests, Institutional, Funding: Pharma Consulting Group AB; Financial Interests, Institutional, Funding: Syneed Medidata; Financial Interests, Institutional, Funding: PPD Global. G. Tortora: Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: AstraZeneca. H. Algül: Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Advisory Role: SERVIER; Financial Interests, Institutional, Funding: Chugai Pharma; Financial Interests, Personal, Other, Travel, accommodations, expenses: Servier. E.M. O'Reilly: Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Cytomx Therapeutics (DSMB); Financial Interests, Personal, Advisory Role: Sobi; Financial Interests, Personal, Advisory Role: Silenseed; Financial Interests, Personal, Advisory Role: Rafael Therapeutics (DSMB); Financial Interests, Personal, Advisory Role: Tyme; Financial Interests, Personal, Advisory Role: Seagen; Financial Interests, Personal, Advisory Role: Molecular Templates; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: BioNTech; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: Polaris; Financial Interests, Personal, Advisory Role: IDEAYA; Financial Interests, Personal, Advisory Role: Cend; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Institutional, Funding: Genentech/Roche; Financial Interests, Institutional, Funding: Celgene/BMS; Financial Interests, Institutional, Funding: BioNTech; Financial Interests, Institutional, Funding: BioAtla; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Arcus; Financial Interests, Institutional, Funding: Elicio; Financial Interests, Institutional, Funding: Parker Institute; Financial Interests, Personal, Advisory Role: Noxxon; Financial Interests, Personal, Advisory Role: BioSapien. S. Bordia: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.. D. McGuinness: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Other, Travel, accommodations, expenses: AstraZeneca. K.Y. Cui: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: Bristol-Myers Squibb. G. Locker: Financial Interests, Personal, Full or part-time Employment, (former employee): AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. H. Kindler: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Five Prime Therapeutics; Financial Interests, Personal, Advisory Role: Paradox Therapeutics; Financial Interests, Personal, Advisory Role: Kyowa Kirin; Financial Interests, Personal, Advisory Role: Astellas Pharma; Financial Interests, Personal, Advisory Role: Inventiva Pharma; Financial Interests, Personal, Advisory Role: Deciphera; Financial Interests, Personal, Advisory Role: Bayern; Financial Interests, Personal, Advisory Role: INHIBRx; Financial Interests, Institutional, Funding: Aduro Biotech; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Bayer; Financial Interests, Institutional, Funding: GlaxoSmithKline; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: Verastem; Financial Interests, Institutional, Funding: Bristol-Myers Squibb; Financial Interests, Institutional, Funding: Lilly; Financial Interests, Institutional, Funding: Polaris; Financial Interests, Institutional, Funding: Deciphera; Financial Interests, Institutional, Funding: INHIBRx; Financial Interests, Institutional, Funding: Polaris; Financial Interests, Institutional, Funding: Blueprint; Financial Interests, Institutional, Funding: Fibrogen.