Does Erlotinib Restore Chemosensitivity to Chemotherapy in Pancreatic Cancer? A Retrospective Analysis

Background Erlotinib, an Epidermal Growth Factor Receptor (EGFR) inhibitor, in combination with gemcitabine was approved in 2005 as 1st-line therapy for patients with Advanced Pancreatic Cancer (APC). In the second line setting, erlotinib as monotherapy and in combination regimens was evaluated in small studies with limited benefit. We previously published a case series documenting a potential benefit of adding erlotinib to chemotherapy at the time of Progression of Disease (PoD) in patients with APC. Here, we update our cohort of patients to a total of 27 diagnosed with APC who received erlotinib upon PoD to prior chemotherapy regimens. Final analysis of this cohort showed a PFS of 4.0 months (range: 2 -11) with median OS of 10.1 months (range: 7 -16). CA19-9 levels declined by greater than 50% in 23% of the patients, by 25 -49% in 19% of the patients, and stable in 26% of the patients. Radiological response included partial response in one patient, and stable disease in 17 patients. Toxicities were manageable, including grade 1-2 rash in 44.4% of patients. Other less common adverse effects were diarrhea (33.3%), anorexia (25.9%), hypomagnesemia (22.2%). Conclusion Our study showed that the addition of erlotinib to prior chemotherapy regimens at PoD provided meaningful disease control with improved PFS. The results confer with the preclinical and clinical findings that the addition of erlotinib may circumvent chemoresistance in chemotherapy-refractory tumors. These findings are like those seen in colorectal cancer following administration of cetuximab in irinotecan-failure patients and warrant prospective studies. Patients and Methods