Efficacy data of oxaliplatin retreatment in patients with metastatic colorectal cancer in a real-world setting.

Abstract

167 Background: Retreatment with oxaliplatin-based regimens after progression to standard therapy, is a common practice in patients with metastatic colorectal cancer (mCRC), although efficacy data are limited. This study aimed to characterize mCRC patients retreated with oxaliplatin in a tertiary hospital. Methods: We reviewed 164 mCRC patients retreated with oxaliplatin from 2015 to 2021. Clinical and molecular data were analyzed. Fisher's exact test, Mann-Whitney U, log-rank test and Cox regression were used for statistical analysis. Results: Most of the patients were male (n=102, 62.2%), with a median age of 63 years. Among them, 73% (n=119) had left-sided tumors, while 35% (n=57) had rectal tumors. 91.5% underwent primary tumor resection, and 66% were diagnosed with metachronous metastatic disease. The predominant metastatic site was the liver (42%), followed by the peritoneum (30%) and lungs (26%). Furthermore, 63% of the patients had only one metastatic site. Regarding molecular profiling, 49% of the patients exhibited KRAS mutations, 11% had BRAF mutations, and 2% had microsatellite instability. Additionally, 57% of the patients underwent adjuvant therapy with oxaliplatin. The median number of lines of systemic treatment administered was four. Compared to the rest of the registry population (n=402), patients retreated with oxaliplatin were younger (63 vs 67 years, p=0.000), had more rectal tumors (34.8% vs 23.1%, p=0.019), and had primary tumors resected (91.5% vs 76.6%). They also displayed higher rates of metachronous metastatic disease (65.9% vs 35.4%, p=0.000) and lung metastases (26.2% vs 17.7%, p=0.028), with a trend towards fewer liver metastases (42.1% vs 50.7%, p=0.064). These patients often had normal CA19.9 (72.5% vs 56%, p=0.001) and LDH levels (81.3% vs 64.4%, p=0.001) at diagnosis, and received more lines of treatment (4 vs 2, p=0.000). Median progression-free survival (mPFS) for retreatment was 7.4 months. The disease control rate (DCR) was 64.5%, with an objective response rate (ORR) of 27.6%. Patients who received adjuvant oxaliplatin had numerically better mPFS (8.47 vs 5.78 months, p=0.27) and DCR (71.9% vs 51.9%, p=0.017). Retreatment beyond third line with oxaliplatin led to poorer mPFS (5.1 vs 7.9 months, p=0.24) and DCR (50% vs 67.8%, p=0.086). No differences in mPFS or DCR were identified regarding sex, age (>70 vs <70 years), or molecular profiling, although there was a trend for better DCR in patients without RAS/BRAF mutations (71.7% vs 59%, p=0.12). Conclusions: Retreatment with oxaliplatin seems to have a greater benefit in patients with prior adjuvant oxaliplatin therapy, treated before third line, and without RAS/BRAF mutations. Age or sex did not affect outcomes.