Efficacy and Toxicity of Panitumumab After Progression on Cetuximab and Predictive Value of MiR-31-5p in Metastatic Wild-type KRAS Colorectal Cancer Patients

Background: In metastatic colorectal cancer (mCRC), panitumumab is generally considered to be ineffective after the progression on cetuximab therapy. However, few studies have demonstrated that a small subset of mCRC patients may benefit from panitumumab in this setting. Patients and Methods: In our study, wild-type KRAS mCRC patients, enrolled into the nationwide Czech registry CORECT between January 2007 and December 2012, were screened for panitumumab therapy after progression on cetuximab. Results: We identified 26 mCRC in the registry with well documented progression on cetuximab in combination with irinotecan-based chemotherapy (FOLFIRI or irinotecan alone) who received panitumumab monotherapy. Partial response (PR) was achieved in 3 (11.5%) patients and stable disease (SD) in 7 (26.9%) patients after 8 weeks of therapy. Thirteen (50.0%) patients had evidence of progressive disease (PD) and in 3 (11.5%) cases response was not available. Furthermore, we confirmed that higher expression levels of newly described biomarker, miR-31-5p, in tumor are significantly associated with shorter progression-free survival (PFS) in patients treated with cetuximab (p=0.038); however, we did not observe association between miR-31-5p and response to panitumumab in mCRC patients after progression on cetuximab. Conclusion: It remains possible that a subset of mCRC patients may benefit from panitumumab after progression on cetuximab.