Phase I/II trial of pimasertib plus gemcitabine in patients with metastatic pancreatic cancer

International Journal of Cancer. Journal International Du Cancer
Eric Van CutsemPascal Hammel

Abstract

The selective MEK1/2 inhibitor pimasertib has shown anti-tumour activity in a pancreatic tumour model. This phase I/II, two-part trial was conducted in patients with metastatic pancreatic adenocarcinoma (mPaCa) (NCT01016483). In the phase I part, oral pimasertib was given once daily discontinuously (5 days on/2 days off treatment) or twice daily continuously (n = 53) combined with weekly gemcitabine (1,000 mg/m2 ) in 28-day cycles to identify the recommended phase II dose (RP2D) of pimasertib. In the phase II part, patients were randomised to pimasertib (RP2D) or placebo plus weekly gemcitabine (n = 88) to investigate progression-free survival (PFS), overall survival (OS) and safety. The RP2D was determined to be 60 mg BID. PFS and OS outcomes did not indicate any treatment benefit for pimasertib over placebo in combination with gemcitabine (median PFS 3.7 and 2.8 months, respectively, HR = 0.91, 95% CI: 0.58-1.42: median OS 7.3 vs. 7.6 months, respectively). KRAS status did not influence PFS or OS. The incidence of grade ≥3 adverse events was 91.1% and 85.7% for pimasertib/gemcitabine and placebo/gemcitabine respectively, but there was a higher incidence of ocular events with pimasertib/gemcitabine (28.9% vs. 4.8% for placebo/...Continue Reading

References

Jun 1, 1997·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·H A BurrisD D Von Hoff
Apr 25, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Malcolm J MooreUNKNOWN National Cancer Institute of Canada Clinical Trials Group
Jun 20, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Asma SultanaPaula Ghaneh
May 13, 2011·The New England Journal of Medicine·Thierry ConroyUNKNOWN PRODIGE Intergroup
Jul 23, 2011·Genes & Cancer·Alberto Fernández-Medarde, Eugenio Santos
Mar 1, 2012·World Journal of Gastroenterology : WJG·Jie-Er YingBi-Xia Liu
Jun 1, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Daniel J RenoufPhilippe L Bedard
Nov 20, 2012·Annals of Oncology : Official Journal of the European Society for Medical Oncology·T SeufferleinUNKNOWN ESMO Guidelines Working Group
Oct 23, 2012·Cancer Metastasis Reviews·Cindy NeuzilletEric Raymond
Apr 16, 2013·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Jeffrey R InfanteAnthony W Tolcher
Sep 21, 2013·The American Journal of the Medical Sciences·Seong Joon ParkTae Won Kim
Oct 18, 2013·The New England Journal of Medicine·Daniel D Von HoffMarkus F Renschler
Jun 12, 2014·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Jeffrey R InfanteNgocdiep Le
Aug 1, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Francesca VenaDaniel Hochhauser
Dec 3, 2016·Gastrointestinal Tumors·Jianwei Zhu, Zhendong Jin

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Citations

Nov 11, 2019·Nature Reviews. Clinical Oncology·Christopher Nevala-PlagemannIgnacio Garrido-Laguna
Jun 24, 2020·The Journal of Clinical Investigation·Paarth B DodhiawalaKian-Huat Lim
Jan 23, 2019·Molecular Cancer·Divya Thomas, Prakash Radhakrishnan
Feb 2, 2020·Nature Reviews. Gastroenterology & Hepatology·Louis BuscailPierre Cordelier
May 7, 2020·International Journal of Molecular Sciences·Kinga B StopaMonika A Jakubowska
Aug 17, 2020·Biomedicines·Friederike Inga Nollmann, Dietrich Alexander Ruess
Feb 24, 2019·The Journal of Pharmacology and Experimental Therapeutics·Fan LeiTatiana K Bronich
Jul 28, 2020·International Journal of Molecular Sciences·Carla Mottini, Luca Cardone
Jun 13, 2020·Nature Reviews. Drug Discovery·Amanda R MooreShiva Malek
Jan 23, 2021·RSC Medicinal Chemistry·Jufeng SunAdam McCluskey
Oct 30, 2020·Journal of Experimental & Clinical Cancer Research : CR·Claudio LuchiniAldo Scarpa
Mar 8, 2021·Seminars in Oncology·Ji Luo
Mar 30, 2021·Frontiers in Oncology·Valeria MerzDavide Melisi
Jun 13, 2021·Cancer Research·Liang YanHaoqiang Ying
Aug 7, 2021·Pharmaceuticals·Alessandro Di FedericoGiovanni Brandi
Aug 17, 2021·Pancreas·Andrew TrunkIgnacio Garrido-Laguna
Nov 4, 2021·Expert Opinion on Investigational Drugs·Byung Woog Kang, Ian Chau

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