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Biweekly cetuximab in combination with capecitabine and oxaliplatin (XELOX) or irinotecan (XELIRI) in the first-line and second-line treatment of patients with RAS wild-type metastatic colorectal cancer

Background: Oral capecitabine in combination with intravenous oxaliplatin (XELOX) or irinotecan (XELIRI) are acceptable substitutions to fully intravenous regimens. Biweekly (as opposed to weekly) cetuximab is more convenient when combined with biweekly chemotherapy. Here, we report the tolerability and efficacy of biweekly cetuximab in combination with biweekly XELOX or XELIRI in patients with RAS wild-type metastatic colorectal cancer (RAS-WT mCRC).

Methods: Clinical data of consecutive patients with mCRC who received biweekly cetuximab (500 mg/m2) in combination with XELOX or XELIRI between January 2009 and May 2019 in the first- or second-line settings was extracted. Dosage of XEL (Capecitabine/XELODA) was 1,000 mg/m2 twice daily for 9 days, plus on day 1 oxaliplatin 85 mg/m2 or irinotecan 180 mg/m2. Treatment dose reduction and delay for ≥7 days was analysed as surrogates for toxicity. Extended RAS testing was performed in the context of this study for patients who received treatment based on limited KRAS-WT genotype.

Results: Sixty one patients with RAS-WT mCRC fulfilled the eligibility criteria. XELOX was administered to 26 (42.6%) and XELIRI to 35 (57.4%) of patients. For all patients in the first-line setting, the objective response rate (ORR), median progression free survival (PFS) and median overall survival (OS) were 54%, 8 months and 25 months, respectively. The corresponding outcomes for the subgroup of patients who received first-line XELOX were 68%, 10 months and not reached, respectively. For all patients in the second-line setting, the ORR, PFS and OS were 50%, 7 months and 20 months, respectively. Chemotherapy components dose reduction and delays were observed in 18 (29.5%) and 25 (41%) patients, respectively. The corresponding frequencies for cetuximab were 3 (5%) and 31 (50.8%).

Conclusion: Biweekly cetuximab in combination with XELOX or XELIRI is tolerable and effective. The addition of cetuximab to capecitabine and oxaliplatin is associated with favourable outcome.

Comments:

This study analyzed the tolerability and efficacy of biweekly cetuximab in combination with biweekly XELOX or XELIRI in patients with RAS wild-type metastatic colorectal cancer (RAS-WT mCRC) who received treatment in the first- or second-line settings between January 2009 and May 2019. The study found that XELOX was administered to 26 (42.6%) patients and XELIRI to 35 (57.4%) patients. The objective response rate (ORR), median progression-free survival (PFS), and median overall survival (OS) were 54%, 8 months, and 25 months, respectively, for all patients in the first-line setting. The corresponding outcomes for the subgroup of patients who received first-line XELOX were 68%, 10 months, and not reached, respectively. For all patients in the second-line setting, the ORR, PFS, and OS were 50%, 7 months, and 20 months, respectively. Chemotherapy components dose reduction and delays were observed in 18 (29.5%) and 25 (41%) patients, respectively, while the corresponding frequencies for cetuximab were 3 (5%) and 31 (50.8%). The study concluded that biweekly cetuximab in combination with XELOX or XELIRI is well-tolerated and effective, and the addition of cetuximab to capecitabine and oxaliplatin is associated with favorable outcomes.

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