Merck's Erbitux Combination Therapy Approved in China as First-Line Treatment for RAS Wild-Type Metastatic Colorectal Cancer

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German pharmaceutical company Merck KGaA recently announced that its targeted anticancer drug Erbitux (Cetuximab) has been approved by the China National Medical Products Administration:

·First-line treatment with FOLFOX (oxaliplatin + leucovorin + 5-FU) or FOLFIRI (irinotecan + leucovorin + 5-FU) in patients with RAS wild-type (wt) metastatic colorectal cancer (mCRC);

·In combination with irinotecan for patients with RAS wild-type metastatic colorectal cancer (mCRC) who are refractory to irinotecan-containing chemotherapy regimens.

This approval is based on the results of the pivotal Phase III clinical study TAILOR. This was a randomized, multicenter, open-label study involving 393 patients with RAS wild-type (wt) metastatic renal cell carcinoma (mRCC) from China. The results demonstrated that, in the first-line treatment of this challenging cancer population, Erbitux in combination with FOLFOX significantly reduced the risk of disease progression or death by 31% compared with FOLFOX alone (hazard ratio [HR]=0.69, p=0.004), reduced the risk of death by 24% (HR=0.76, p=0.02), and substantially improved the overall response rate (61.1% vs. 39.5%; odds ratio [OR]=2.41, p<0.001). The safety profile of Erbitux observed in this study was consistent with that reported in previous randomized clinical studies, with no unexpected safety findings.

The TAILOR study was the first Phase III trial conducted in the Chinese population, designed to evaluate the role of anti-epidermal growth factor receptor (EGFR) antibodies as first-line treatment in patients with RAS wild-type (wt) metastatic colorectal cancer (mCRC), and to reinforce the value and importance of RAS biomarker testing in clinical practice, thereby ensuring that patients receive the appropriate targeted therapy from the outset of treatment. These data are consistent with previous international pivotal studies and reaffirm the efficacy of Erbitux in combination with FOLFOX as first-line treatment for patients with RAS wt mCRC.

For a long time, Erbitux combined with chemotherapy has been a standard care regimen for treating RAS wt mCRC. The TAILOR study further demonstrated the potential of this regimen as a first-line treatment.

Colorectal cancer is the third most common cancer globally and the second leading cause of cancer-related deaths. It is estimated that worldwide, over 1.85 million new cases are diagnosed annually, with 880,000 deaths. In metastatic CRC cases, RAS wild-type and mutant tumors each account for half.

The distinction between Erbitux and standard non-selective chemotherapy lies in its targeted binding to EGFR, which inhibits receptor activation and subsequent signal transduction, thereby reducing tumor cell invasion into normal tissues and metastasis to new sites. Furthermore, Erbitux is believed to inhibit the ability of tumor cells to repair damage induced by chemotherapy and radiotherapy, as well as to suppress intratumoral angiogenesis, thus achieving comprehensive inhibition of tumor growth. In vitro studies have demonstrated that Erbitux can also direct cytotoxic immune effector cells toward EGFR-expressing tumor cells.

Erbitux is the world’s first IgG1 monoclonal antibody targeting EGFR. Launched in 2003, it has been approved in more than 100 countries/regions worldwide for the treatment of RAS wild-type metastatic colorectal cancer (RAS wt mCRC) and/or squamous cell carcinoma of the head and neck. Erbitux was developed by ImClone (now a wholly owned subsidiary of Eli Lilly), and Merck KGaA obtained exclusive rights to Erbitux in markets outside the United States and Canada through a licensing agreement in 1998.

In China, Erbitux was approved in 2006 for the treatment of RAS wild-type metastatic colorectal cancer (mCRC). The drug has been included in Category B of the 2019 edition of the National Reimbursement Drug List, with a reimbursement payment standard of CNY 1,295 per bottle [100 mg (20 mL)/bottle].

References:

1、ERBITUX in Combination with FOLFOX or FOLFIRI Approved as First-Line Therapy for Patients in China with RAS Wild-Type Metastatic Colorectal Cancer

2. Notice of the National Healthcare Security Administration and the Ministry of Human Resources and Social Security on Issuing the "National Drug Catalogue for Basic Medical Insurance, Work-Related Injury Insurance, and Maternity Insurance"