Found 1 Presentation For Request "1298p"
1298P - Extended overall survival results from the POLO study of active maintenance olaparib in patients with metastatic pancreatic cancer and a germline BRCA mutation
- Pascal Hammel (Paris, France)
Abstract
Background
The POLO study (NCT02184195) demonstrated a significant progression-free survival (PFS) benefit for active maintenance olaparib (O) relative to placebo (P) for patients (pts) with metastatic pancreatic cancer and a germline BRCA mutation (hazard ratio [HR]: 0.53, 95% confidence interval [CI]: 0.35–0.82;
Methods
Pts (N = 154) were randomized 3:2 to O (300 mg tablets b.i.d.; n = 92) or P (n = 62). The primary endpoint was PFS by blinded independent central review; secondary endpoints included OS, investigator-PFS, time to treatment discontinuation (TDT) and time to first and second subsequent therapies (TFST; TSST). HRs and 95% CIs were calculated using a log-rank test.
Results
At DCO3, 26 pts (16.9%) remained in the study (O: 20.7%; P: 11.3%). The proportions of pts who remained on O or P were 38.9% vs 9.8% at 1 year, 24.4% vs 3.3% at 2 years, 16.4% vs 3.3% at 3 years and 13.5% vs 3.3% at 4 years. The OS result at DCO3 remained similar to that at DCO2 (HR: 0.79; 95% CI: 0.55–1.15). However, the KM curves separated clearly from 24 months after randomization (estimated O and P survival rates: 34.4% vs 15.7% at 3 years; 23.9% vs 15.7% at 4 years; 19.2% vs 10.5% at 5 years). In total, 7.6% and 27.4% of pts in the O and P arms, respectively, received a subsequent PARP inhibitor. Investigator-PFS, TDT, TFST and TSST were longer for O than for P (table). Safety results were consistent with DCO2.
Median, months HR (95% CI) Olaparib Placebo OS 19.0 19.2 0.79 (0.55–1.15) Investigator-PFS 6.7 3.7 0.50 (0.34–0.75) TDT 7.5 3.8 0.44 (0.30–0.65) TFST 9.0 5.3 0.48 (0.32–0.70) TSST 14.9 9.6 0.59 (0.41–0.86)
Conclusions
The HR for OS continued to favour O, although the 95% CI overlapped 1.0. The results indicate an unprecedented durable response to O in a subset of patients.
Clinical trial identification
NCT02184195, release date: 6 June 2014.
Editorial acknowledgement
Stephen Sweet, PhD, of Oxford PharmaGenesis, Oxford, UK, provided medical writing assistance supported by AstraZeneca and Merck Sharp & Dohme, a subsidiary of Merck & Co, Inc, Kenilworth, NJ, USA, who are codeveloping olaparib.
Legal entity responsible for the study
AstraZeneca and Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc, Kenilworth, NJ, USA.
Funding
AstraZeneca and Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc, Kenilworth, NJ, USA.
Disclosure
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, Institutional, Funding: Erytech Pharma, AstraZeneca, Halozyme; Financial Interests, Personal, Other, Travel, accommodations, expenses: Halozyme, Pfizer, Vect-Horus; Financial Interests, Personal, Other: Bristol Myers Squibb; Non-Financial Interests, Personal, Other: Ipsen, Novartis. T. Golan: Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Advisory Role: AbbVie, AstraZeneca, Bayer, MSD, Teva; Financial Interests, Personal, Speaker’s Bureau: AbbVie, AstraZeneca; Financial Interests, Institutional, Funding: AstraZeneca, MSD. M. Reni: Financial Interests, Personal, Advisory Role: Celgene, Baxalta/Shire, Lilly, AstraZeneca, Sanofi, Baxter, MSD, Servier; Financial Interests, Institutional, Funding: Celgene; Financial Interests, Personal, Other, Travel, accommodation, expenses: 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 Sharp & Dohme, 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, Institutional, Funding: Celgene, Agios, ASLAN Pharmaceuticals, Bayer, Roche, Genentech, AstraZeneca, Halozyme, Immunomedics, Lilly, Merrimack, Millennium, Novartis, Novocure, Pfizer; Financial Interests, Personal, Other, Travel, accommodations, expenses: Merck Sharp & Dohme, H3 Biomedicine, Sanofi, Celgene, Servier. M. Hall: Financial Interests, Personal, Funding: InVitae, Foundation Medicine, Caris Life Sciences, Myriad Genetics, AstraZeneca, Ambry Genetics; Financial Interests, Institutional, Royalties, shared patent with several Fox Chase investigators for a novel method to investigate hereditary CRC genes (Inst): Fox Chase; Financial Interests, Personal, Other: Foundation Medicine, Caris Life Sciences, Myriad Genetics, AstraZeneca. J.O. Park: Financial Interests, Personal, Advisory Role: Celgene, Bristol Myers Squibb, AstraZeneca, Merck Serono, MedPacto, Servier, Adicet Bio, Bayer; Financial Interests, Personal, Funding: Celgene, Bristol Myers Squibb, MedPactor, Servier. D. Hochhauser: Financial Interests, Personal, Stocks/Shares: Roche, Novartis; Financial Interests, Personal, Speaker’s Bureau: Pierre Fabre; Financial Interests, Personal, Funding: Merck Serono; Financial Interests, Personal, Other: Celgene. D. Arnold: Financial Interests, Institutional, Research Grant: Abbvie; Financial Interests, Personal, Invited Speaker: ACE Oncology; Amgen; Aptitude Health; art tempi media; Astra Zeneca; Bayer; Boston Scientific; Bristol Myers Squibb; Clinical Care Options; Eli Lilly; From Research to Practice; Imedex; Ipsen; MedAhead (Austria); Merck Serono; Merck, Sharp and Dome; Pharm; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb; Pierre Fabre Pharma; Roche; Non-Financial Interests, Personal, Project Lead: OncoLytics; Financial Interests, Personal, Advisory Board: Bayer; Terumo; Bristol-Myers Squibb; AstraZeneca; CRA International – Consulting Agency; Hexal; IQVIA – Consulting; Ketchum – Consulting Agency; Merck, Sharp and Dome; Pierre Fabre Pharma; Roche; Samsung Bioepsis; Sanofi (Genzyme); Financial Interests, Personal, Other: Elsevier – Roles as Assoc. Editor for ESMO Open and Ann Oncol Elsevier; Oxford University Press – Roles as Associate Editor Ann Oncol; Elsevier – Role as Associate Editor Clin Colorect Cancer; Financial Interests, Institutional, Other: Sanofi (Genzyme) – DSMB chair; Non-Financial Interests, Personal, Leadership Role: GI Group Steering Committee; Steering Committee Member; Non-Financial Interests, Personal, Member: ASCO; ESO; DGHO. 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, 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, Personal, Advisory Role: Amgen, Roche, Pfizer, Sanofi/Aventis, Merck Serono, Celgene, Bristol Myers Squibb, Servier, Baxalta, MSD, Onkowissen, AstraZeneca, Pierre Fabre; Financial Interests, Institutional, Funding: Roche, Celgene, Ipsen, Amgen, Alexion Pharmaceuticals, AstraZeneca, Lilly, Servier, AIO-Studien, Georgius Agricola Stiftung Ruhr, Mologen AG, Ludwig Maximilian University of Muni; Financial Interests, Personal, Invited Speaker, Travel, accommodations, expenses: Ipsen, Amgen, Celgene, Onkowissen, Roche, Servier, MCI Group, Pierre Fabre, AstraZeneca, Merck Serono, MSD. G. Tortora: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, Celgene, MSD, AstraZeneca. H. Algül: Financial Interests, Personal, Advisory Role: Celgene, Servier; Financial Interests, Institutional, Funding: Chugai Pharma; Financial Interests, Personal, Other, Travel, accommodation, expenses: Servier. E. O'Reilly: Financial Interests, Personal, Advisory Role: Cytomx Therapeutics (DSMB), Rafael Therapeutics (DSMB), Sobi, Silenseed, Tyme, Seagen, Molecular Templates, Boehringer Ingelheim, BioNTech, Ipsen, Polaris, Merck, IDEAYA, Cend, AstraZeneca, Noxxon, BioSapien, Cend Therapeutics, Research to Practice, ; Financial Interests, Personal, Advisory Role, Advisory role (an immediate family member): Bayer, Genentech/Roche, Celgene/BMS, Eisai, AstraZeneca; Financial Interests, , Invited Speaker: Genentech/Roche, Celgene/BMS, BioNTech, BioAtla, AstraZeneca, Arcus, Elicio, Parker Institute, Pertzye. K. Sharan: Financial Interests, Personal, Full or part-time Employment: Merck. X. Ou: Financial Interests, Personal, Full or part-time Employment: 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, Stocks/Shares: AstraZeneca. H. Kindler: Financial Interests, Personal, Advisory Role: AstraZeneca, Merck Sharp & Dohme, Boehringer-Ingelheim, Inventiva, Deciphera, Bayer, INHIBRx, Bristol Myers Squibb, Novocure, Seattle Genetics; Financial Interests, Institutional, Funding: Aduro Biotech, AstraZeneca, Bayer, GlaxoSmithKline, Merck Sharp & Dohme, Verastem, Bristol Myers Squibb, Lilly, Polaris, Deciphera, INHIBRx, Blueprint, Inventiva, Harpoon, Macrogenics, Seattle Genetics.