Pemetrexed plus erlotinib as a salvage treatment in high EGFR-expressing metastatic colorectal cancer patients following failure of standard chemotherapy: A phase II single-arm prospective study.

104 Background: We conducted a single-arm, phase II study to evaluate the combination of pemetrexed and erlotinib as a salvage treatment in high EGFR-expressing (2+ or 3 on immunohistochemistry (IHC)) metastatic colorectal cancer (CRC) patients who failed to show a benefit after standard chemotherapy. Methods: We investigated pemetrexed and erlotinib (pemetrexed 500 mg/m2 on Day 1 and erlotinib 100 mg/m2 on Days 1–21) as a salvage treatment, given every three weeks, until disease progression or intolerable toxicity. The primary outcome was overall response rate (RR). Results: From May 2017 to April 2018, 29 metastatic CRC patients with high EGFR expression who previously received the 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 only grades 1 or 2. In 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 an expression of EGFR 3+ in a tumor. Among eight patients with a tumor expressing an EGFR value of 3+, the RR and DCR were 37.5% and 75.0%, respectively. Conclusions: This phase II trial using pemetrexed and erlotinib in metastatic CRC with high EGFR expression met the primary endpoint of tumor response. Clinical trial information: NCT03086538.