Nab-paclitaxel plus gemcitabine in patients with locally advanced pancreatic cancer (LAPACT): a multicentre, open-label phase 2 study.

Autor:	Philip PA; Department of Oncology, Karmanos Cancer Institute, Wayne State University, Hudson-Webber Cancer Research Center, Detroit, MI, USA. Electronic address: philipp@karmanos.org., Lacy J; Internal Medicine, Yale School of Medicine, New Haven, CT, USA., Portales F; Department of Digestive Oncology, Institut du Cancer de Montpellier, Montpellier, France., Sobrero A; Medical Oncology, IRCCS Ospedale San Martino IST, Genoa, Italy., Pazo-Cid R; Department of Medical Oncology, Hospital Universitario Miguel Servet, Zaragoza, Spain., Manzano Mozo JL; Department of Medical Oncology, Hospital Germans Trias i Pujol, Institut Català d'Oncologia Badalona, Barcelona, Spain., Kim EJ; Department of Internal Medicine, UC Davis School of Medicine, University of California Davis, Sacramento, CA, USA., Dowden S; Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada., Zakari A; Department of Internal Medicine, AdventHealth Cancer Institute, Orlando, FL, USA., Borg C; Department of Medical Oncology, University Hospital of Besançon, Besançon, France., Terrebonne E; Department of Gastroenterology, CHU Haut-Lévêque, Pessac, France., Rivera F; Department of Medical Oncology, Hospital Universitario Marqués de Valdecilla, Santander, Spain., Sastre J; Department of Medical Oncology, Hospital Clínico San Carlos, Madrid, Spain., Bathini V; Division of Hematology/Oncology, UMass Memorial Medical Center, Worcester, MA, USA., López-Trabada D; Department of Medical Oncology, Hôpital Saint Antoine, Paris, France., Asselah J; Department of Oncology, McGill University Royal Victoria Hospital, Montréal, QC, Canada., Saif MW; Medical Oncology, Northwell Health Cancer Institute, Lake Success, NY, USA., Shiansong Li J; Celgene Corporation, Summit, NJ, USA., Ong TJ; Celgene Corporation, Summit, NJ, USA., Nydam T; Celgene Corporation, Summit, NJ, USA., Hammel P; Department of Pancreatology, Hôpital Beaujon (AP-HP), Université Denis Diderot-Paris VII, Clichy, France.
Jazyk:	angličtina
Zdroj:	The lancet. Gastroenterology & hepatology [Lancet Gastroenterol Hepatol] 2020 Mar; Vol. 5 (3), pp. 285-294. Date of Electronic Publication: 2020 Jan 14.
DOI:	10.1016/S2468-1253(19)30327-9
Abstrakt:	Background: Treatment options for patients with unresectable locally advanced pancreatic cancer are scarce. Results from a subanalysis of the phase 3 MPACT trial in metastatic pancreatic cancer suggested potential activity of nab-paclitaxel plus gemcitabine against locally advanced pancreatic cancer. The objective of this phase 2 trial was to evaluate safety and efficacy of nab-paclitaxel plus gemcitabine in previously untreated locally advanced pancreatic cancer. Methods: This international, open-label, multicentre, phase 2 trial (LAPACT) took place at 35 sites in five countries (USA, France, Spain, Canada, and Italy). Patients with Eastern Cooperative Oncology Group performance status of up to 1 underwent six cycles of induction with nab-paclitaxel 125 mg/m 2 plus gemcitabine 1000 mg/m 2 (days 1, 8, and 15 of each 28-day cycle). After induction, patients without progressive disease or unacceptable adverse events were eligible to receive continued therapy per investigator's choice: continued nab-paclitaxel plus gemcitabine, chemoradiation, or surgery. The primary endpoint was time to treatment failure; secondary endpoints were disease control rate, overall response rate, progression-free survival, overall survival, safety, and quality of life. The reported efficacy outcomes were analysed in the intention-to-treat population, and safety outcomes were analysed in the treated population. This trial is registered with ClinicalTrials.gov, NCT02301143, and EudraCT, 2014-001408-23 and is complete. Findings: Between April 21, 2015, and April 26, 2018, 107 patients were enrolled in the study. 106 received the study treatment; one patient enrolled but did not receive treatment. 44 (41%) of 107 enrolled patients discontinued induction; the most common reason for discontinuing induction was adverse events (22 [21%] patients). 62 (58%) of 107 enrolled patients completed induction treatment and 47 (44%) patients subsequently received continued treatment per investigator's choice: 12 (11%) continued nab-paclitaxel plus gemcitabine, 18 (17%) received chemoradiation, and 17 (16%) underwent surgery (seven had R0 resection status, nine had R1). 15 (14%) patients completed induction treatment but did not receive continued treatment. Median time to treatment failure was 9·0 months (90% CI 7·3-10·1); median progression-free survival was 10·9 months (90% CI 9·3-11·6), and median overall survival was 18·8 months (90% CI 15·0-24·0). During induction, 83 patients achieved disease control and the disease control rate was 77·6% (90% CI 70·3-83·5). 36 patients had a best response of partial response; the overall response rate during induction was 33·6% (90% CI 26·6-41·5). The most common treatment-emergent adverse events that were grade 3 or higher in the treated population during induction were neutropenia (35 [33%] of 106 patients), anaemia (12 [11%]), and fatigue (11 [10%]). The most common treatment-emergent serious adverse events during induction were pneumonia (five [5%] patients), pyrexia (five [5%]), and febrile neutropenia (three [3%]). No deaths were caused by treatment-related adverse events during the induction phase, and global quality of life was maintained in most patients. Interpretation: The data from this trial support the tolerability and activity of nab-paclitaxel plus gemcitabine for locally advanced pancreatic cancer, and a potential to convert unresectable, locally advanced disease to surgically resectable disease. The safety profile was generally consistent with previous findings. Funding: Celgene. (Copyright © 2020 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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