A phase II clinical trial of prior regimen rechallenge in third- or later-line treatment for patients with metastatic colorectal cancer

e15583 Background: Current choices of systemic treatment for patients with metastatic colorectal cancer remained limited, with some patients facing drugless conditions after failure of standard treatment. For those who have responded to the front-line treatment, there is a lack of data from prospective studies, on whether reapplication of former regimens in the later line can still bring clinical benefits. We conducted an exploratory study to evaluate the efficacy and safety of prior regimen rechallenge in the third or later-line treatment in patients with metastatic colorectal cancer (mCRC). Methods: This is a single-arm prospective phase II study (ClinicalTrials.gov Identifier: NCT03485027). The key inclusion criteria were:(1) histologically confirmed mCRC; (2) treatment failure to at least two lines of systemic chemotherapy; progression free survival (PFS) of the rechallenged regimen should be at least four months in the prior setting without unrecoverable toxicity; (3) the time interval between the re-applied chemotherapy regimen and its previous administration was at least 6 months. Eligible patients received the reapplication regimens, including XELOX, FOLFOX, FOLFIRI, Irinotecan monotherapy with or without targeted drug, which was formerly used. Evaluation was repeated every 6 weeks and treatment continues until the disease progression or intolerable adverse effects. The primary end point is PFS. The secondary endpoint is overall survival (OS), objective response rate (ORR), disease control rate (DCR) and treatment safety. Results: From Jan 24, 2018 to Dec 24, 2022, a total of 53 patients were recruited, and 51 patients who had received at least one cycle of rechallenged medication were included in this analysis. The median age was 59 (range 36-82) years old. Among these patients, 38 were administrated with the combination of targeted and chemotherapy as the rechallenge regimen (24 with bevacizumab plus chemotherapy and 14 with cetuximab plus chemotherapy), and 13 with chemotherapy alone (7 with oxaliplatin-based chemotherapy and 6 with irinotecan-based chemotherapy). A total of 41 patients had received the efficacy evaluation after treatment. One patient achieved partial response (tumor change from baseline -38.4%), 23 patients with stable disease and 17 patients with progressive disease. The ORR and DCR were 2.4% and 58.5%, respectively. At the last follow-up date on Jan 31, 2023, the median PFS was 4.0 months (95% CI, 2.62–5.38). The data of OS was still immature. Grade 3 or 4 adverse events were reported in 6 patients (11.76%). The detailed grade 3 or 4 adverse events were neutropenia in 4 patients, oxaliplatin related acute anaphylaxis in 2 patients, diarrhea in 2 patients. Conclusions: For the patients with heavily treated mCRC, the re-application of chemotherapy with front-line treatment regimen has shown a decent effectiveness with acceptable safety. Clinical trial information: NCT03485027 .