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CCR2 Inhibitor Active in Combination With FOLFIRINOX in Advanced Pancreatic Cancer

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Key Points

  • CCR2 inhibitor treatment appeared to be well tolerated in treatment-naive patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma.
  • Response was observed in half of patients receiving CCR2 inhibitor treatment plus FOLFIRINOX.

A CCR2 inhibitor (PF-04136309) was active in combination with FOLFIRINOX (oxaliplatin, irinotecan, leucovorin, fluorouracil) in treatment-naive patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma, according to a single-center phase Ib study reported by Nywening et al in The Lancet Oncology.

The CCL2–CCR2 chemokine axis acts to recruit tumor-associated macrophages in the development of an immunosuppressive tumor microenvironment in pancreatic ductal adenocarcinoma. Blockade of CCR2 has been found to restore antitumor immunity in preclinical models.

Toxicity

In the study, 47 patients at Washington University School of Medicine were treated with FOLFIRINOX alone (n = 8) or with an oral CCR2 inhibitor daily (n = 39) for 12 weeks.

Of the six patients receiving FOLFIRINOX plus PF-04136309 at 500 mg twice daily during the dose-finding phase, one patient had a dose-limiting toxicity; this dose, used in the expansion-phase group of 33 patients, was selected as the recommended phase II dose.

No treatment-related deaths occurred. Two patients (5%) in the FOLFIRINOX plus PF-04136309 group stopped treatment earlier than planned due to treatment-related toxicity. The most common grade ≥ 3 adverse events occurring in patients receiving PF-04136309 were neutropenia (69%), febrile neutropenia (18%), hypokalemia (18%), and diarrhea (15%); grade ≥ 3 adverse events in six evaluable patients receiving FOLFIRINOX alone included neutropenia in 100%, hypokalemia in 50%, anemia in 33%, diarrhea in 33%, and febrile neutropenia in 17%.

Responses

Among 33 patients receiving FOLFIRINOX plus PF-04136309 who underwent repeat imaging, 16 (49%) had an objective tumor response, with local tumor control achieved in 32 (97%). Among five patients receiving FOLFIRINOX alone with repeat imaging, none achieved an objective response, with four (80%) exhibiting stable disease.

The investigators concluded: “CCR2-targeted therapy with PF-04136309 in combination with FOLFIRINOX is safe and tolerable.”

The study was funded by Washington University–Pfizer Biomedical Collaborative.

David C. Linehan, MD, of the University of Rochester Medical Center, is the corresponding author of The Lancet Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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