CCR2 Inhibition Combined With FOLFIRINOX Safe for Pancreatic Cancer

Share this content:
CCR2-targeted therapy in combination with FOLFIRINOX is safe and tolerable in patients with pancreatic ductal adenocarcinoma.
CCR2-targeted therapy in combination with FOLFIRINOX is safe and tolerable in patients with pancreatic ductal adenocarcinoma.

CCR2-targeted therapy with investigational PF-04136309 in combination with FOLFIRINOX (fluorouracil, leucovorin, irinotecan, oxaliplatin) chemotherapy is safe and tolerable in patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma.1

Preclinical models have demonstrated that blockade of CCR2, which plays a role in the recruitment of tumor-associated macrophages for construction of an immunosuppressive tumor microenvironment, restores anti-tumor immunity in pancreatic cancer.

Therefore, researchers sought to establish the safety, tolerability, and recommended phase 2 oral dose of the CCR2 inhibitor PF-04136309 in combination with FOLFIRINOX.

For the single-center, open-label, dose-finding, phase 1b study, researchers enrolled 47 treatment-naïve patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma.

Patients were assigned to receive either FOLFIRINOX alone (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2, and bolus fluorouracil 400 mg/m2, followed by 2400 mg/m2 46-hour continuous infusion), administered every 2 weeks for 6 cycles, or in combination with oral PF-04136309, given at a starting dose of 500 mg twice daily, both for 12 weeks.

Researchers determined that the 500 mg twice daily dose would be the recommended phase 2 dose for PF-04136309.

Results showed that the most common grade 3 or worse adverse events in the CCR2 inhibitor group were neutropenia, febrile neutropenia, lymphopenia, diarrhea, and hypokalemia.

RELATED: Identification of 4 Pancreatic Cancer Subtypes Could Lead to New, Personalized Treatments

Two patients discontinued combination therapy due to treatment-related toxicities compared with 1 patient in the FOLFIRINOX alone group. Of note, no treatment-related death occurred.

In regard to activity, 49% of the 33 receiving FOLFIRINOX plus PF-04136309 who had undergone repeat imaging achieved an objective response, with 97% of the 33 patients achieving local tumor control. No patients in the chemotherapy alone group achieved an objective response, but 80% had stable disease.

Reference

  1. Nywening TM, Wang-Gillam A, Sanford DE, et al. Targeting tumour-associated macrophages with CCR2 inhibition in combination with FOLFIRINOX in patients with borderline resectable and locally advanced pancreatic cancer: a single-centre, open-label, dose-finding, non-randomised, phase 1b trial [published online ahead of print April 4, 2016]. Lancet Oncol. doi: 10.1016/S1470-2045(16)00078-4.

Related Resources

You must be a registered member of Cancer Therapy Advisor to post a comment.

Regimen and Drug Listings

GET FULL LISTINGS OF TREATMENT Regimens and Drug INFORMATION

Bone Cancer Regimens Drugs
Brain Cancer Regimens Drugs
Breast Cancer Regimens Drugs
Endocrine Cancer Regimens Drugs
Gastrointestinal Cancer Regimens Drugs
Gynecologic Cancer Regimens Drugs
Head and Neck Cancer Regimens Drugs
Hematologic Cancer Regimens Drugs
Lung Cancer Regimens Drugs
Other Cancers Regimens
Prostate Cancer Regimens Drugs
Rare Cancers Regimens
Renal Cell Carcinoma Regimens Drugs
Skin Cancer Regimens Drugs
Urologic Cancers Regimens Drugs

Sign Up for Free e-newsletters