1298P - Extended overall survival results from the POLO study of active maintenance olaparib in patients with metastatic pancreatic cancer and a germline BRCA mutation

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; p = 0.004; data cut-off 1 [DCO1]). In the final overall survival (OS) analysis (DCO2), the HR for OS favoured olaparib without reaching statistical significance (HR: 0.83; 95% CI: 0.56–1.22; p = 0.3487). Here, we present an exploratory extended OS analysis, carried out 12 months after the final OS analysis (DCO3).

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. Table: 1298P

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. 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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.