Nab-paclitaxel Plus Gemcitabine in Patients with Locally Advanced Pancreatic Cancer (LAPACT): A Multicenter, Open-label Phase II Study
Philip A Philip, Jill Lacy, Fabienne Portales, Alberto Sobrero, Roberto Pazo-Cid, José L Manzano Mozo, Edward J Kim, Scot Dowden, Ahmed Zakari, Christophe Borg, Eric Terrebonne, Fernando Rivera, Javier Sastre, Venu Bathini, Daniel López-Trabada, Jamil Asselah, Muhammad Wasif Saif, Jack Shiansong Li, Teng Jin Ong, Thomas Nydam, Pascal Hammel.
Department of Oncology, Karmanos Cancer Institute, Wayne State University, Hudson-Webber Cancer Research Center, Detroit, MI, USA. Electronic address: firstname.lastname@example.org. Internal Medicine, Yale School of Medicine, New Haven, CT, USA. Department of Digestive Oncology, Institut du Cancer de Montpellier, Montpellier, France. Medical Oncology, IRCCS Ospedale San Martino IST, Genoa, Italy. Department of Medical Oncology, Hospital Universitario Miguel Servet, Zaragoza, Spain. Department of Medical Oncology, Hospital Germans Trias i Pujol, Institut Català d'Oncologia Badalona, Barcelona, Spain. Department of Internal Medicine, UC Davis School of Medicine, University of California Davis, Sacramento, CA, USA. Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. 9Department of Internal Medicine, AdventHealth Cancer Institute, Orlando, FL, USA. Department of Medical Oncology, University Hospital of Besançon, Besançon, France. Department of Gastroenterology, CHU Haut-Lévêque, Pessac, France. Department of Medical Oncology, Hospital Universitario Marqués de Valdecilla, Santander, Spain. Department of Medical Oncology, Hospital Clínico San Carlos, Madrid, Spain. Division of Hematology/Oncology, UMass Memorial Medical Center, Worcester, MA, USA. Department of Medical Oncology, Hôpital Saint Antoine, Paris, France. Department of Oncology, McGill University Royal Victoria Hospital, Montréal, QC, Canada. Medical Oncology, Northwell Health Cancer Institute, Lake Success, NY, USA. Celgene Corporation, Summit, NJ, USA. Department of Pancreatology, Hôpital Beaujon (AP-HP), Université Denis Diderot-Paris VII, Clichy, France.
Background: Treatment options for patients with unresectable locally advanced pancreatic cancer are scarce. Results from a subanalysis of the Phase III MPACT trial in metastatic pancreatic cancer suggested potential activity of nab-paclitaxel plus gemcitabine against locally advanced pancreatic cancer. The objective of this Phase II trial was to evaluate safety and efficacy of nab-paclitaxel plus gemcitabine in previously untreated locally advanced pancreatic cancer.
Methods: This international, open-label, multi-center, Phase II 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/m2 plus gemcitabine 1000 mg/m2 (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 analyzed in the intention-to-treat population, and safety outcomes were analyzed 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.
For more information or to refer a patient, call Gastrointestinal Oncology Nurse Navigators Erica Corcoran, MSN, RN, OCN, AOCNS, ONN-CG, at 407-303-5981, or Wyntir Purtha, BSN, RN, OCN, at 407-303-5959.