Multi-drug inhibition of the HER pathway in metastatic colorectal cancer: results of a phase I study of pertuzumab plus cetuximab in cetuximab-refractory patients.

摘要: Purpose Resistance to cetuximab, a monoclonal antibody against the epithelial growth factor receptor (EGFR), in colorectal cancer (CRC) may result from compensatory signaling through ErbB receptors, ErbB2/neu/HER2 (HER2) and ErbB3/HER3 (HER3). Pertuzumab is that blocks HER2 hetero-dimerization; thus combination of pertuzumab cetuximab could possibly overcome resistance. Patients methods This single-arm, open-label, multicenter phase I/II study was designed assess safety efficacy patients with cetuximab-resistant KRAS wild type metastatic CRC. Thirteen were enrolled received at several dose levels 3 + 3 design. assessed for dose-limiting toxicity (DLT) during first cycle. A II portion planned, but not initiated due toxicity. Results Six thirteen (46 %) experienced DLTs, therefore terminated early. Grade 3 or higher DLTs included dermatitis desquamation and/or acneiform rash (n = 6), mucositis stomatitis (n = 5), diarrhea (n = 2). There one 5 event (myocardial infarction) attributed underlying disease. Among 13 patients, seven (54 %) evaluable response. The objective response rate 14 %: patient had partial lasting 6 months. Two stable disease (29 %), four progressive (57 %). Median progression free survival 2.1 months (95 % CI, 1.5–4.9) median overall 3.7 months 1.6–7.9). Conclusion Combination refractory CRC associated potential antitumor activity; however, tolerable overlapping toxicities.