FDA Approves New Dose of Cetuximab for KRAS Wild-Type, EGFR Expressing mCRC or SCCHN

The FDA has approved a higher dose of cetuximab for the treatmen of patients with KRAS wild-type, EGFR-expressing metastatic colorectal cancer or squamous cell carcinoma of the head and neck.

The FDA has approved a new cetuximab (Erbitux) dose of 500 mg/m2 to be administered by 120-minute intravenous (IV) infusion every two weeks to patients with KRAS wild-type, EGFR-expressing metastatic colorectal cancer (mCRC) or squamous cell carcinoma of the head and neck (SCCHN), announced the FDA, in a press release.1

With this newly approved dosage of cetuximab, providers will have a biweekly dosing option for patients in addition to the previously approved weekly dosing option. Cetuximab can be dosed alone or in combination with chemotherapy.

Pharmacokinetic analyses of cetuximab 500 mg/m2 versus 250 mg weekly served as the basis for the FDA approval of a higher dose along with pooled data from real-world trials of cetuximab as treatment of patients with either CRC and SCCHN, in which positive overall survival (OS) and progression-free survival (PFS) data were shown at both dosing levels.

For the SCCHN population treated in the phase 3 EXTREME trial (NCT00122460) of cetuximab combined with platinum chemotherapy and fluorouracil in 442 patients with recurrent locoregional disease or metastatic SCCHN, the median OS was 10.1 with the combination compared with 7.4 months with platinum and fluorouracil alone (HR, 0.80; 95% CI, 0.64-0.9; = .034). The median PFS 5.5 months with cetuximab plus platinum chemotherapy and fluorouracil versus 3.3 months with only platinum chemotherapy and fluorouracil (HR, 0.57; 95% CI. 0.46, 0.72; P <.0001). Moreover, responses were higher with cetuximab combination at 35.6% compared with 19.5% with the chemotherapy-only combination (odds ratio, 2.33; 95% CI, 1.50, 3.60; P =.0001).2

A cohort of 1217 patients with KRAS wild-type, EGFR-expressing mCRC treated with cetuximab in combination with the FOLFIRI regimen (Irinotecan, fluorouracil [5-FU], and folinic acid [leucovorin]) in the CRYSTAL trial (NCT00154102) achieved a median PFS of 8.9 months (95% CI, 8.0- 9.4) with the addition of cetuximab compared with 8.1 months (95% CI, 7.6, 8.8) with FOLFIRI alone (HR, 0.85, 95 % CI, 0.74-0.99; P =.0358). The median OS was 19.6 months (95% CI, 18-21) with the cetuximab combination versus 18.5 months (95% CI, 17- 20) with FOLFIRI alone (HR, 0.88; 95% CI, 0.78-1.0). A slightly higher objective response rate was also observed with the addition of cetuximab (46%) compared with the FOLFIRI-alone arm (38%).

The most common adverse events experienced in patients who receive cetuximab are cutaneous AEs which include rash, pruritus, and nail changes). Cases of headache, diarrhea, and infection may also occur with the drug. These AEs can occur in ≥25% of patients. Other toxicities like infusion reaction, cardiopulmonary arrest, pulmonary toxicity, hypomagnesemia and accompanying electrolyte abnormalities, and embryo-fetal toxicity have been observed with cetuximab in studies.1,2

The FDA approval of cetuximab 500 mg/m2 was granted 5 months ahead of the FDA target action date.1


1. FDA approves new dosing regimen for cetuximab. News release. FDA. April 6, 2021. Accessed April 7, 2021. https://bit.ly/3unSnGi

2. Highlights of prescribing information. Accessed April 7, 2021. https://bit.ly/3ux6klq