Comparative efficacy of commonly used first-line chemotherapy regimens in advanced pancreatic cancer: A network meta-analysis.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 403-403
Author(s):  
Philip A. Haddad ◽  
Kevin Michael Gallagher ◽  
Dalia Hammoud

403 Background: Pancreatic adenocarcinoma is one of the deadliest cancers, ranking fourth in mortality and accounting for up to 7% of all cancer related deaths in the United States. For many years, Gemcitabine and its combinations have been the standard first-line treatments for patients with unresectable locally advanced or metastatic pancreatic cancer (aPC). Recently, FOLFIRINOX was shown to be associated with a survival advantage as well. These chemotherapy combinations have not been compared to each other. We conducted this network meta-analysis to evaluate the relative efficacy of the commonly used chemotherapy regimens in patients with aPC. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language; diagnosis of aPC; treatment with Gemcitabine (GEM) combined with Capecitabine (CAPE), Erlotinib (ERLO), or nab-Paclitaxel (NABPAC) and treatments with FOLFIRINOX; and randomized studies reporting survival and response rates. A frequentists network meta-analysis was conducted using netmeta package and random-effects model. Results: Six studies comprising a total of 2,717 participants were included. FOLFIRINOX demonstrated a significantly better relative risk (RR) of progression and death (P&D) followed by GEM+NABPAC, GEM+ERLO, GEM+CAPE, and GEM in a decreasing order. When compared to GEM-based combination as a group, FOLFIRINOX maintained its superior RR for P&D. Moreover, FOLFIRINOX and GEM+NABPAC had significantly better response rates than GEM+CAPE and GEM+ERLO. Inconsistency analysis did not reveal any significant differences between direct and indirect estimates. Conclusions: This network meta-analysis is the first to compare and rank commonly used treatment regimens in aPC. It indicates that FOLFIRINOX combination seems to be superior to GEM-based combinations with respect to P&D as well as response rates. Nevertheless, among GEM-based combinations, GEM+NABPAC seems to have the best profile given its lower RR for P&D and higher response rates.

2017 ◽  
Vol 11 (2) ◽  
pp. 422-427 ◽  
Author(s):  
Sarah Hahn ◽  
Ahmet Ayav ◽  
Anthony Lopez

The incidence of pancreatic cancer has dramatically increased over the past years, but the prognosis has not improved. Between 30 and 40% of tumors are considered locally advanced, essentially due to vascular involvement. In recent years, new chemotherapy protocols with high response rates have been developed. FOLFIRINOX seems to be an interesting option in this situation, but hematologic toxicity could be an obstacle to its prescription. Nab-paclitaxel and gemcitabine offer significant response rates with a reasonable safety profile. We report here a single-center experience of 2 cases with a locally advanced pancreatic cancer initially considered unresectable, progressive after first-line neoadjuvant FOLFIRINOX chemotherapy, and then treated with second-line nab-paclitaxel/gemcitabine chemotherapy.


2021 ◽  
Author(s):  
Jingwen Chen ◽  
Yiqian Liu ◽  
Yizhi Zhu ◽  
Shiyun Cui ◽  
Chongqi Sun ◽  
...  

Abstract Background There have not been standard second-line or maintenance regimens with definite survival benefits so far for patients with pancreatic carcinoma who have lost the opportunity of curable resections or failed first-line chemotherapy. Anlotinib, a potent small-molecule tyrosine kinase inhibitor, exhibits anti-angiogenic and anti-tumour effects by specifically binding to multiple targets such as VEGFR, FGFR, PDGFR, c-Kit and Ret. Toripalimab, a novel anti-PD-1 mAb, has been proved to significantly prolong progression-free survival (PFS) and overall survival (OS) in various solid tumours with manageable toxicities when combining with cytotoxic chemotherapy. We design this study to assess the combination of anlotinib, toripalimab and nab-paclitaxel as a second-line or maintenance therapy for locally advanced pancreatic cancer (LAPC) or metastatic pancreatic cancer (MPC). Patients and Methods: This is an open-label, non-randomized, single-arm phase Ⅱ study, aimed at evaluating the efficacy and safety profile of the above-mentioned combination strategy in first-line therapy-failed LAPC or MPC. Totally 53 patients are to be enrolled and receive anlotinib (12 mg, po. qd.) plus toripalimab (240 mg, ivgtt. q3w.) and nab-paclitaxel (125 mg/m2, ivgtt, d1, d8) every 3 weeks as a cycle until disease progression or intolerable adverse events. The primary endpoint is PFS. Secondary end points include OS, disease control rate (DCR), object response rate (ORR), quality of life (QoL) and safety. Enrollment started in April 2021, and follow-up will be finished in April 2023. Discussion and Significance: Combination of anlotinib, toripalimab and nab-paclitaxel may promote vessel normalization and drug delivery, and activate the immune response, thus exerting synergistic anti-tumour effects and counteracting the immunosuppressive microenvironment of pancreatic cancer. As the first intending to assess this combination in pancreatic cancer, this study will provide comprehensive evidence for second-line or maintenance therapy of LAPC and MPC. Trial registration: ClinicalTrials.gov: ATNPA, NCT04718701. Registered January 22, 2021. (https://clinicaltrials.gov/ct2/show/NCT04718701?term=NCT04718701&draw=2&rank=1)


2019 ◽  
Author(s):  
Francis Igor Macedo ◽  
Danny Yakoub ◽  
Vikas Dudeja ◽  
Nipun B. Merchant

The incidence of pancreatic cancer continues to rise, and it is now the third-leading cause of cancer-related deaths in the United States. Only 15 to 20% of patients are eligible to undergo potentially curative resection, as most tumors are deemed unresectable at the time of diagnosis because of either locally advanced disease or distant metastases. Improvements in preoperative CT imaging have enabled better determination of the extent of disease and allowed for better operative planning. Based on their relationship to the surrounding vasculature and structures and presence or absence of distant disease, pancreatic tumors are classified into four categories: resectable, borderline resectable pancreatic cancer (BRPC), locally advanced pancreatic cancer (LAPC), and metastatic. With the recent advent of more effective chemotherapy regimens, efforts have focused on using neoadjuvant therapy approaches to increase the likelihood of achieving an R0 in patients with BRPC and possibly convert unresectable, locally advanced tumors to potentially resectable tumors. Response with neoadjuvant therapy regimens has resulted in increased number of patients eligible for resection, many times requiring vascular resection. Herein, we describe recent changes in the classification, important surgical and pathologic considerations and updated multimodal therapeutic options in the complex management of BRPC and LAPC.  This review contains 5 figures, 2 tables, and 78 references. Key Words: borderline resectable pancreatic cancer, CA 19-9, FOLFIRINOX, locally advanced pancreatic cancer, nab-paclitaxel, neoadjuvant chemotherapy, pancreatectomy, portal vein resection, radiation therapy, gemcitabine


2011 ◽  
Vol 99 (2) ◽  
pp. 108-113 ◽  
Author(s):  
Chang-Peng Zhu ◽  
Jian Shi ◽  
Yue-Xiang Chen ◽  
Wei-Fen Xie ◽  
Yong Lin

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6607-6607
Author(s):  
Thomas H. Cartwright ◽  
Aimee Ginsburg Arlen ◽  
Lalan S. Wilfong ◽  
Robyn K. Harrell ◽  
J. Russell Hoverman ◽  
...  

6607 Background: Pancreatic cancer (PC) is the fourth leading cause of death in the United States. It is estimated that 45,220 patients will be diagnosed in 2013 and 38,460 will die (Siegel, CA Cancer J Clin 2013). Gemcitabine has long been the standard of care chemotherapy. Recent advances in treatment created a combination regimen (oxaliplatin, irinotecan, leucovorin, fluorouracil [FOLFIRINOX]) for patients with good Karnofsky performance status (PS) (Conroy, NEJM 2011). This retrospective analysis was conducted as an update to results reported at ASCO 2012 (Ginsburg Arlen, JCO 2012) to evaluate characteristics and overall survival (OS) of patients receiving FOLFIRINOX and gemcitabine-based treatments in a large outpatient community setting. This is the largest study describing FOLFIRINOX patients to date. Methods: Patients with advanced PC treated within The US Oncology Network entered into the iKnowMed (iKM) database between June 2010 and November 2012 were included. Patterns of treatment were characterized by the median age at diagnosis, sex, PS, and first-line metastatic chemotherapy prescribed. The primary endpoints of the analysis were OS and uptake of FOLFIRINOX within the network. Results: Compared to ASCO 2012 results, 1,000 additional patients were identified in iKM. Of the 1,714 total patients, 24% received FOLFIRINOX (up from 13% in 2012) and 76% gemcitabine-based therapy (87% in 2012). Increased utilization of FOLFIRINOX for patients with good PS began in June 2010. For all patients (55% male), the median age at diagnosis was 67 years and the majority (85%) had a PS of 70% or greater. The OS was significantly longer for FOLFIRINOX (9.6 mos) versus gemcitabine (6.3 mos) (p<0.0001). This held true for PS of 70% or greater patient given FOLFIRINOX (9.6 mos) versus gemcitabine (7 mos) (p<0.0001). Conclusions: Utilization of FOLFIRINOX has continued to expand after the publication of phase III trials. Our data in a community setting supports a survival advantage for FOLFIRINOX. Although the magnitude of benefit may be smaller in the community, we agree that FOLFIRINOX should become a standard of care for good PS patients.


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