The addition of erlotinib to gemcitabine and cisplatin does not appear to improve median survival in metastatic pancreatic cancer

Abstract

Metastatic pancreatic cancer carries a poor prognosis, with median survival on the order of several months. There is evidence that combining gemcitabine with either erlotinib or cisplatin may be superior to single agent gemcitabine in patients with good performance (PS 0-1). We retrospectively compared outcomes of patients treated with either the three drug regimen of gemcitabine, cisplatin, and erlotinib (GCE) or the doublet of gemcitabine and cisplatin (GC) in order to assess the potential benefit of erlotinib. We also evaluated the role of erlotinib among smokers and non-smokers. We retrospectively analyzed 145 patients who presented between 2006 and 2009 with previously untreated metastatic pancreatic cancer initially treated at the M.D. Anderson cancer center with either GC or GCE. Information on tumor characteristics and overall survival time (OS) was collected by medical record review. Kaplan-Meier curves were used to estimate OS. Log rank tests were used to compare OS between groups. The Cox proportional hazards regression model was used to evaluate the ability of patient prognostic variables or treatment group to predict OS. A total of 71 patients were treated with GC, while 74 were treated with GCE. Cox analyses found no significant difference in overall survival (median 5.5 vs. 8.0 months, respectively, p-value=0.1). Small sampling numbers may have contributed to this result. One year survival was 23 % in the GCE group and 13 % in the GC group. Patients with poor performance status (PS=2-3) had worse survival as compared to patients with better performance status (PS=0-1, p=0.001). As in earlier studies, patients treated with more lines of therapy tended to have better survival (p <0.0001), and CA19-9 was found to be a significant predictor for OS (p=0.001). No statistical evidence of a survival difference was found between smokers and non-smokers in both treatment groups (p=0.72). In conclusion, though there was a trend towards improved survival with the addition of erlotinib to gemcitabine and cisplatin, this does not reach statistical significance.

Phase 1 trial evaluating cisplatin, gemcitabine, and veliparib in 2 patient cohorts: Germline BRCA mutation carriers and wild‐type BRCA pancreatic ductal adenocarcinoma

“…We chose this dose and schedule to 1) preserve the platinum dose, 2) minimize the myelosuppressive impact of the combination by reducing the gemcitabine dose, 3) permit the addition of the PARPi, and 4) allow a treatment that could be administered for a prolonged period. Despite the lower dose of gemcitabine, the dose intensity of gemcitabine, when calculated, was comparable to that of standard approaches . A key principle underpinning the hypothesis is that a combination strategy would delay the emergence of resistance by overcoming the limitations of a single‐agent targeted approach.…”

“…[17][18][19][20][21] A randomized phase 3 trial with gemcitabine and cisplatin for advanced biliary cancers supported the use of gemcitabine at 1000 mg/m 2 and cisplatin at 25 mg/m 2 on days 1 and 8 every 3 weeks; however, lower doses of gemcitabine have previously been demonstrated to have activity against advanced PDAC. 22,23 We chose to evaluate a fixed cisplatin dose of 25 mg/m 2 and a fixed gemcitabine dose of 600 mg/m 2 and to dose-escalate veliparib. Although cisplatin plus gemcitabine may have limited activity against PDAC absent a homologous recombination defect, we hypothesized that it would be an effective regimen for BRCA1 patients and for an enriched patient population (surrogate family/personal history of cancer).…”

“…Despite the lower dose of gemcitabine, the dose intensity of gemcitabine, when calculated, was comparable to that of standard approaches. 23 A key principle underpinning the hypothesis is that a combination strategy would delay the emergence of resistance by overcoming the limitations of a single-agent targeted approach.…”

Molecular Targeted Intervention for Pancreatic Cancer

“…Khalil et al retrospectively compared the outcomes of patients treated with either the three-drug regimen of gemcitabine, cisplatin, and erlotinib (GCE), or gemcitabine combined with cisplatin (GC), in order to assess the potential benefit of erlotinib. One-year survival was 23% in the GCE group, and 13% in the GC group [ 112 ]. Although there was a trend toward improved survival with GCE, the trend did not reach statistical significance, since the sample size was small.…”

Antitumor effects of herbal mixture extract in the pancreatic adenocarcinoma cell line PANC1

“…Gemcitabine affects the S phase of cell cycle, preventing cell division, and has proven to be effective for symptom management and prolonged survival in advanced pancreatic cancer (8). Recent clinical trials of combination therapy with gemcitabine and another agent had statistical significance, but not significant enough for patients (9)(10)(11).…”