1467P - POLO: Long-term safety and tolerability of olaparib for patients with a germline BRCA mutation and metastatic pancreatic cancer

Background

The phase III POLO trial (NCT02184195) compared maintenance PARP inhibitor therapy with olaparib (O) to placebo (P) in patients (pts) with a germline BRCA mutation and metastatic pancreatic cancer. We describe safety and tolerability results for pts with an overall survival (OS) of ≥ 2 years.

Methods

Pts were randomized 3:2 to maintenance O (300 mg tablets b.i.d.; n = 92) or P (n = 62) until disease progression or unacceptable toxicity. The safety analysis set (SAS) comprised all pts who received at least one dose of study medication. Long-term survivors were those with an OS of ≥ 24 months after randomization at data cut-off (21 July 2020). Adverse events (AEs) were reported up to 30 days post study treatment, graded using CTCAE v4.03.

Results

In total, 34 pts (37.0%) on O and 17 pts (27.4%) on P were long-term survivors. Median durations of study treatment among these pts were 25.9 and 7.3 months in the O and P arms, respectively, compared with 7.5 and 3.7 months in the SAS. A total of 4 long-term survivors in the P arm (23.5%) and 5 in the O arm (14.7%) received a subsequent PARP inhibitor after study treatment discontinuation. The Table compares safety outcomes in long-term survivors with those in the SAS. In the O arm, the proportions of pts who experienced common O-related AEs (fatigue/asthenia, nausea, anaemia and vomiting) were similar among long-term survivors (61.8%, 58.8%, 32.4% and 29.4%, respectively) and the SAS (63.3%, 48.9%, 32.2% and 25.6%), but were higher than among long-term survivors in the P arm (29.4%, 35.3%, 17.6% and 23.5%). AEs were commonly managed through dose modification. In the O arm, four long-term survivors (11.8%) received a blood transfusion to treat anaemia and one (2.9%) received epoetin beta. Table: 1467P

Safety summary of AEs (SAS and long-term survivors)

AE, adverse event; CTCAE, Common Terminology Criteria for Adverse Events v4.03; SAE, serious adverse event; SAS, safety analysis set.

Conclusions

Duration of O was > 3-fold longer for long-term survivors than for the SAS, but proportions of pts experiencing AEs were similar. AEs were more common among long-term survivors on O than on P, and were managed mostly by dose modification.

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

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