Sequential first-line treatment with nab-paclitaxel/gemcitabine and FOLFIRINOX in metastatic pancreatic adenocarcinoma: GABRINOX phase Ib-II controlled clinical trial

ESMO Open

article

E. Assenat¹  C. de la Fouchardière³  F. Portales¹  M. Ychou¹  A. Debourdeau²  F. Desseigne³  S. Iltache²  C. Fiess¹  C. Mollevi⁶  T. Mazard¹ 

[1] Medical Oncology Department, Montpellier Cancer Institute ,(ICM), University of Montpellier;CHU Montpellier, University of Montpellier;Medical Oncology Department, Léon Bérard Centre;Institut de Recherche en Cancérologie de Montpellier ,(IRCM), INSERM U1194, University of Montpellier;Clinical Research and Innovation Department, Montpellier Cancer Institute ,(ICM), University of Montpellier;Biometrics Unit, Montpellier Cancer Institute ,(ICM), University of Montpellier;Institut Desbrest d"Epidémiologie et de Santé Publique ,(IDESP), INSERM UMR UA 11, University of Montpellier

关键词: pancreatic cancer;    adenocarcinoma;    nab-paclitaxel;    gemcitabine;    FOLFIRINOX;    metastasis;   

DOI  :  10.1016/j.esmoop.2021.100318

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background Nab-paclitaxel/gemcitabine (AG) and FOLFIRINOX (FFX) are promising drugs in metastatic pancreatic cancer (MPC). This study evaluated a new first-line sequential treatment (AG followed by FFX) in MPC that might overcome resistance to primary therapy and delay tumor progression.Patients and methods Patients with histologically/cytologically confirmed MPC were included in a multicentric trial receiving AG (day 1, 8 and 15) followed by FFX (day 29 and 43). In phase Ib, three dose-levels were tested for maximum tolerated dose (MTD) and recommended phase II dose. In phase II, the main outcome was the objective response rate (ORR) and secondarily safety, progression-free survival (PFS) and overall survival (OS).Results In phase Ib, we included 33 patients (31 assessable) of median age 61.0 years (range 42-75 years) and represented by 54.8% males. Five dose-limiting toxicities were reported without any death. The main grade 3/4 toxicities were neutropenia with spontaneous resolution (35.5%/32.3%), venous thromboembolism (grade 3: 22.6%) and thrombopenia (grade 3: 29.0%), while the MTD was not reached. In phase II, we included 58 patients of median age 60 years (range 34-72 years), 50% males and with Eastern Cooperative Oncology Group stage score 0 and 1 of 37.9% and 62.1%, respectively. They received a median of 4 (1-9) cycles in 8.5 months (0.5-19.8 months). The ORR was 64.9% [95% confidence interval (CI) 51.1% to 77.1%], and neurotoxicity was remarkably low. The main grade 3-4 toxicities were venous thromboembolism, thrombopenia, neutropenia/febrile neutropenia, nausea, diarrhea, weight loss and asthenia without any death. Tumor response was complete in 3.5% and partial in 61.4%, while disease was stable in 19.3% and progressive in 15.8% of patients. The median PFS was 10.5 months (95% CI 6.0-12.5 months) and median OS was 15.1 months (95% CI 10.6-20.1 months).Conclusion Sequential AG and FFX showed acceptable toxicity as first-line treatment with no limiting neurotoxicity, while high response rate and survival justify randomized trials.

【 授权许可】

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