Pemetrexed/Erlotinib as a Salvage Treatment in Patients with High EGFR-Expressing Metastatic Colorectal Cancer Following Failure of Standard Chemotherapy: A Phase II Single-Arm Prospective Study.

Abstract

Despite new agents to treat metastatic colorectal cancer (CRC), patients eventually progress andadditional therapies are needed. We intended to evaluate the combination of pemetrexed/erlotinib in patients with high epidermal growth factor receptor (EGFR)-expressing (2+ or 3 on immunohistochemistry) metastatic CRC who experienced disease progression after standard chemotherapy. We investigated pemetrexed and erlotinib (pemetrexed 500mg/m2 on Day 1 and erlotinib 100mg/m2 on Days 1-21) as a salvage treatment, given every 3weeks, until disease progression or intolerable toxicity. The primary outcome was overall response rate (RR). From May 2017 to April 2018, 29 metastatic CRC patients with high EGFR expression who had previously received standard therapies were enrolled into this trial. The regimen was well tolerated. Skin rash, vomiting, fatigue, and anorexia were common toxic effects but were mostly manageable and controllable side effects of grades 1 or 2 only. In an intent-to-treat analysis, three partial responses (PRs) were observed in enrolled patients, revealing an overall RR of 10.3%. This value supported the statistical hypothesis of this study. Fifteen patients had stable disease and the disease control rate (DCR) was 62.1%. All three patients who achieved a PR had a tumor EGFR expression of 3+. Among the eight patients with EGFR 3+ expression, the RR and DCR were 37.5% and 75.0%, respectively. This phase II trial using pemetrexed/erlotinib in metastatic CRC with high EGFR expression met the primary endpoint of tumor response. This study was registered at ClinicalTrials.gov (number NCT03086538).