Cetuximab β Plus FOLFIRI Displays Significant Clinical Activity in First-Line mCRC

Cetuximab β Plus FOLFIRI in First-Line mCRC

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Treatment with cetuximab β (Enlituo; formerly CMAB009)—a modified antibody of cetuximab (Erbitux), plus 5-fluorouracil (5-FU), leucovorin, and irinotecan (FOLFIRI)—led to prolonged progression-free survival (PFS) and overall survival (OS) vs FOLFIRI alone in patients with RAS/BRAF wild-type metastatic colorectal cancer (mCRC).

Data from a phase 3 study (NCT03206151) published in Signal Transduction and Targeted Therapy showed that at median follow-ups of 8.7 months (95% CI, 7.77-9.29) and 5.9 months (95% CI, 5.63-6.65) in the cetuximab β plus FOLFIRI (n = 257) and FOLFIRI monotherapy (n = 248) arms, respectively, the median PFS was 13.1 months (95% CI, 11.2-14.0) and 9.6 months (95% CI, 7.9-11.3), respectively (HR, 0.639; 95% CI, 0.468-0.872; log-rank P = .004). The median OS was 28.3 months (95% CI, 24.0-38.1) vs 23.1 months (95% CI, 19.6-24.5), respectively (HR, 0.729; 95% CI, 0.551-0.965; log-rank P = .024).

“This study achieved its primary end point, with a statistically significant difference in blinded independent review committee [BICR]-assessed PFS between the 2 treatment groups. The investigator-assessed PFS and other sensitivity analyses confirmed the robustness of this positive outcome,” the study authors wrote.

In June 2024, cetuximab β in combination with FOLFIRI was approved by China’s National Medical Products Administration for the frontline treatment of patients with RAS/BRAF wild-type mCRC.²

Diving Into the Study Design and Baseline Characteristics

Theopen-label, multicenter, parallel-group study enrolled Chinese patients with histologically confirmed RAS/BRAF wild-type mCRC who were not eligible for radical resection and had not received prior systemic chemotherapy or had finished chemotherapy at least 12 months before metastasis.¹ Patients were also required to have at least 1 measurable lesion per RECIST 1.1 criteria; an ECOG performance status of 0 or 1; and adequate hematologic, hepatic, and renal function.

Eligible patients were randomly assigned 1:1 to receive cetuximab β plus FOLFIRI or FOLFIRI monotherapy. Cetuximab β was administered at an initial loading dose of 400 mg/m² on days 1 and 8 of each cycle followed by a weekly maintenance dose of 250 mg/m². Patients in both arms received intravenous (IV) irinotecan at dose of 180 mg/m², followed by 400 mg/m² of IV leucovorin and a bolus IV dose of 5-FU at a dose of 400 mg/m² on the first day of each cycle, followed by a continuous IV infusion of 5-FU at a dose of 2400 mg/m².

The primary end point was PFS per BICR assessment. Secondary end points included OS, objective response rate (ORR), disease control rate (DCR), surgery rate for metastasis and R0 resection rate, and safety.

At baseline, the median ages in the combination and monotherapy arms were 57 years (range, 23-74) and 58 years (range, 23-75), respectively. Most patients in both arms had an ECOG performance status of 1 (66.9% vs 67.3%), metastatic sites at the liver (69.6% vs 76.2%), and left-sided tumors (85.6% vs 85.9%). Patients had 1 (33.1% vs 28.6%), 2 (37.0% vs 33.5%), 3 (17.9% vs 21.8%), or more than 3 (12.1% vs 16.1%) metastatic sites.

Additional Efficacy Results and Safety Data

Additional findings revealed that the ORR in the combination arm was 69.1% (95% CI, 63.2%-75.0%) compared with 42.3% (95% CI, 35.9%-48.7%) in the monotherapy arm (OR, 3.090; 95% CI, 2.280-4.189; P < .001). The DCRs were 88.0% (95% CI, 83.8%-92.2%) and 89.9% (95% CI, 85.9%-93.8%), respectively (OR,0.814; 95% CI, 0.477-1.389; P = .520). The surgery rates for metastasis with curative intent were 7.4% and 1.6%, respectively (P = .002). The R0 resection rates were 4.7% and 1.2%, respectively (P = .640).

Regarding safety, grade 3 or higher treatment-emergent adverse effects were reported in 83.3% of patients in the combination arm and 66.9% of patients in the FOLFIRI monotherapy arm. Grade 3 or higher treatment-related adverse effects (TRAEs) were reported in 78.6% and 57.3% of patients, respectively. The most common grade 3 or higher TRAEs in both arms included decreased absolute neutrophil counts (56.8% vs 34.7%), decreased white blood cell counts (32.7% vs 16.5%), and diarrhea (10.1% vs 12.5%).Cetuximab β–induced infusion-related reactions occurred in 12.8% of patients.

“[Data from] this study demonstrated that cetuximab β plus FOLFIRI provided significant clinical benefits as a first-line treatment for patients with RAS/BRAF wild-type mCRC,” the study authors wrote in their conclusion. “Compared [with] FOLFIRI alone, cetuximab β plus FOLFIRI therapy led to prolonged median PFS and OS while maintaining a manageable safety profile, offering a new treatment option for this patient population.”

References

1. Shi Y, Ba Y, Wang J, et al. First-line treatment of anti-EGFR monoclonal antibody cetuximab β plus FOLFIRI versus FOLFIRI alone in Chinese patients with RAS/BRAF wild-type metastatic colorectal cancer: a randomized, phase 3 trial. Signal Transduct Target Ther. 2025;10(1):147. doi:10.1038/s41392-025-02229-4
2. Simcere Zaiming announce approval of cetuximab beta in China by the NMPA. News release. Simcere Zaiming. June 26, 2024. Accessed May 15, 2025. https://www.simcere.com/en/news/detail.aspx?mtt=459