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Objective: Pembrolizumab, a PD-1 inhibitor, demonstrated anti-tumour activity and tolerability in patients treated with sorafenib and with advanced hepatocellular carcinoma in KEYNOTE-224. Longer-term efficacy and safety after ∼2.5 years of additional follow-up are reported., Patients and Methods: Adults with confirmed hepatocellular carcinoma who experienced progression after or intolerance to sorafenib treatment received pembrolizumab 200 mg every 3 weeks for ≤35 cycles or until confirmed progression, unacceptable toxicity, withdrawal of consent or investigator decision. The primary end-point was objective response rate assessed by blinded independent central review per Response Evaluation Criteria in Solid Tumours v1.1. The secondary end-points included duration of response, disease control rate, time to progression, progression-free survival, overall survival and adverse events., Results: Efficacy and safety were assessed in 104 patients. The median time from first dose to data cutoff was 45.1 months (range, 41.3-49.3). Objective response rate was 18.3% (95% CI: 11.4-27.1), and median duration of response was 21.0 months (range, 3.1 to 39.5+). Disease control rate was 61.5%, and median time to progression was 4.8 months (95% CI: 3.9-7.0). Median progression-free survival was 4.9 months (95% CI: 3.5-6.7) and median overall survival was 13.2 months (95% CI: 9.7-15.3). Of 104 patients, 76 (73.1%) patients reported treatment-related adverse events; most were low grade in severity (grade 3-4, n = 26 [25.0%]; grade 5, n = 1 [1.0%]). Immune-mediated hepatitis occurred in 3 patients (all grade 3). No viral-induced hepatitis flares occurred., Conclusions: After ∼2.5 years of additional follow-up, pembrolizumab continued to provide durable anti-tumour activity and no new safety concerns were identified., Gov Identifier: NCT02702414., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M. Kudo has received a grant and fees from Eisai, and Bristol Myers Squibb; has received fees from Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Eli Lilly; has served a consultant for Bayer, Eisai, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Roche, Bristol Myers Squibb, and Ono; and has received a grant from Otsuka, Taiho, EA Pharma, Takeda, Gilead, AbbVie, and Sumitomo Dainippon Pharma; R.S. Finn has received fees and a grant to his institution from Merck, Bayer, Eli Lilly, Bristol Myers Squibb, Eisai, Pfizer, Roche/Genentech; and has received fees from AstraZeneca and CStone; J. Edeline has received personal fees from Bayer, Bristol Myers Squibb, AstraZeneca, Eisai, Ipsen, Boston Scientific, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; and has received grants from Bristol Myers Squibb, BeiGene, and Boston Scientific; S. Cattan has nothing to disclose; S. Ogasawara has received a grant and fees from Bayer, Eisai, Eli Lilly; and has received fees from Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, AstraZeneca, and Chugai; D. Palmer has received a grant and fees from Bristol Myers Squibb, NuCana Inc, and Sirtex; has received a grant from AstraZeneca; and has received fees from Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Roche, and Eisai; C. Verslype has received a grant from Baye and Ipsen and has served as a consultant for Bayer, Ipsen, and Roche; V. Zagonel has served in an advisory capacity or as a consultant for Bristol Myers Squibb and Merck; has served as a speaker for Bayer, Roche, Bristol Myers Squibb, Astellas Pharma, SERVIER, AstraZeneca, Eli Lilly; and has received travel, accommodations, and expenses from Bayer, Roche, and SERVIER; L. Fartoux has no conflicts of interest to report. A. Vogel has received fees for serving in an advisory capacity/consultant, has received speaking fees, has received fees for expert testimony, and has received honoraria from AstraZeneca, Bayer, Bristol Myers Squibb, BTG, Eli Lilly, Incyte Corporation, Ipsen, Janssen, Merck, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Novartis, Pierre Fabre, Roche, Sanofi, and Servier; D. Sarker has received fees from Eisai, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, AstraZeneca, Bayer, and Surface Oncology; has received fees and non-financial support from Ipsen; has received non-financial support from MiNA Therapeutics; and has received a grant from Roche; G. Verset has received a grant from Terumo; has served as a consultant for Terumo and BTG; has served in an advisory capacity for Bayer, Eisai, and Roche; and has received travel expenses for attending congresses from Bayer, Bristol Myers Squibb, and Ipsen; S.L. Chan has participated as an advisor for AstraZeneca; J. Knox has received a grant for an investigator-initiated study from Merck; and has received fees for consulting from Merck, Ipsen, and Roche; B. Daniele has received fees from Ipsen, Eisai, Eli Lilly, AstraZeneca, Sanofi, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Bayer, Roche, and Amgen; and has received non-financial support from Ipsen, Bristol Myers Squibb; T. Yau has received fees for serving in an advisory capacity or as a consultant and has received honoraria from Bristol Myers Squibb, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Exelixis, Ipsen, Eisai, AstraZeneca, Bayer, Novartis, EMD Serono, AbbVie, Pfizer, Eli Lilly, Sirtex, SillaJen, Taiho, OrigiMed, New Beta Innovation, Sirtex, and H3 Biomedicine; E.B. Gurary and A. B. Siegel are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; A. Wang is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA and has stock in Merck & Co., Inc., Kenilworth, NJ, USA; A-L Cheng has received fees for consulting from AstraZeneca, Bristol Myers Squibb, Eisai, Merck Serono, Novartis, Ono Pharmaceutical, Exelixis, Nucleix, Ipsen Innovation, Bayer Healthcare, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Roche/Genentech, BeiGene, CSR Pharma Group, F Hoffmann-La Roche, and IQVIA; has received travel support from Roche/Genentech, IQVIA, and Bayer Yakuhin; and has received speaker fees from Eisai, Novartis, Ono Pharmaceutical, Bayer Yakuhin, and Amgen Taiwan; A.X. Zhu has received fees for consulting from Merck, Eli Lilly, Bayer, Sanofi, Eisai, Exelixis, and Roche., (Copyright © 2022 Masatoshi Kudo, Richard S. Finn, Julien Edeline, Stéphane Cattan, Sadahisa Ogasawara, Daniel H. Palmer, Chris Verslype, Vittorina Zagonel, Laetitia Fartoux, Arndt Vogel, Debashis Sarker, Gontran Verset, Stephen L. Chan, Jennifer Knox, Bruno Daniele, Thomas Yau, Ellen B. Gurary, Abby B. Siegel, Anran Wang, Ann-Lii Cheng, Andrew X. Zhu, KEYNOTE-224 Investigators. Published by Elsevier Ltd.. All rights reserved.)

The most common metastatic sites of pancreatic cancer are the liver, lymph nodes, peritoneum and lung. Here we report two cases of BRCA mutated pancreatic cancer that developed unusual metastasis while treatment with maintenance Olaparib and leading to rapid death. We hereby review the literature and address the possibility of a different nature and tumour biology of BRCA mutated cancer treated with PARP inhibitors., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)