Benefits from early trial involvement in metastatic colorectal cancer: outcomes from the phase I unit at the Sarah Cannon Research Institute UK

•Phase I trials are a valuable option for chemorefractory CRC.•Outcomes are comparable with approved third-line treatments (ORR 7%, CBR 47%).•Left-sidedness, adjuvant therapy and primary surgery noted improved OS. BackgroundMetastatic colorectal cancer (CRC) is associated with poor overall survival (OS) and limited activity of approved therapeutics following two standard lines of chemotherapy. Participation in phase I trials could offer an alternative treatment option; however, benefit from participation remains unclear.Materials and methodsMedical records of patients enrolled in phase I trials at the Sarah Cannon Research Institute UK between October 2011 and July 2022 were reviewed. Patients who had received at least one dose of investigational therapy were included. Patient demographics, tumor histopathologic and molecular characteristics, clinical outcomes, including objective response rate (ORR) and clinical benefit rate (CBR), and drug details were assessed using descriptive statistics and univariable and multivariable analyses.ResultsOf 1796 patients screened for phase I trials, 80 CRC patients from 31 phase I trials of 27 distinct investigational agents were included in the analysis. Overall, 53.8% were men, median age was 59 years (range 31-80 years) and median number of prior lines was 2 (range 1-6 prior lines). Median follow-up was 7 months (range 0.3-70.8 months). ORR was 7% 95% confidence interval (CI) 3.3% to 15.7% and CBR 47% (95% CI 40.3% to 62%) across all trials. Median OS was 16.8 months (95% CI 8.8-22.0 months). The 12-month survival rate was 58%. Subgroup assessment demonstrated better outcomes for subjects receiving immunotherapies, while multivariable logistical regression demonstrated increased OS for surgery on the primary tumor hazard ratio (HR) 0.05 (95% CI 0.00-0.69), P = 0.03, low lymphocyte/monocyte ratio HR 0.45 (95% CI 0.20-0.95), P = 0.04 and left-sidedness HR 0.10 (95% CI 0.14-0.70), P = 0.02.ConclusionsPhase I trials may provide relevant benefits for patients with refractory CRC with comparable survival to third-line therapies. Early consideration of phase I involvement may provide expedited access to potential future standard-of-care options. Metastatic colorectal cancer (CRC) is associated with poor overall survival (OS) and limited activity of approved therapeutics following two standard lines of chemotherapy. Participation in phase I trials could offer an alternative treatment option; however, benefit from participation remains unclear. Medical records of patients enrolled in phase I trials at the Sarah Cannon Research Institute UK between October 2011 and July 2022 were reviewed. Patients who had received at least one dose of investigational therapy were included. Patient demographics, tumor histopathologic and molecular characteristics, clinical outcomes, including objective response rate (ORR) and clinical benefit rate (CBR), and drug details were assessed using descriptive statistics and univariable and multivariable analyses. Of 1796 patients screened for phase I trials, 80 CRC patients from 31 phase I trials of 27 distinct investigational agents were included in the analysis. Overall, 53.8% were men, median age was 59 years (range 31-80 years) and median number of prior lines was 2 (range 1-6 prior lines). Median follow-up was 7 months (range 0.3-70.8 months). ORR was 7% 95% confidence interval (CI) 3.3% to 15.7% and CBR 47% (95% CI 40.3% to 62%) across all trials. Median OS was 16.8 months (95% CI 8.8-22.0 months). The 12-month survival rate was 58%. Subgroup assessment demonstrated better outcomes for subjects receiving immunotherapies, while multivariable logistical regression demonstrated increased OS for surgery on the primary tumor hazard ratio (HR) 0.05 (95% CI 0.00-0.69), P = 0.03, low lymphocyte/monocyte ratio HR 0.45 (95% CI 0.20-0.95), P = 0.04 and left-sidedness HR 0.10 (95% CI 0.14-0.70), P = 0.02. Phase I trials may provide relevant benefits for patients with refractory CRC with comparable survival to third-line therapies. Early consideration of phase I involvement may provide expedited access to potential future standard-of-care options.