Cetuximab effective in advanced cutaneous squamous cell carcinoma

By Reuters Staff

NEW YORK (Reuters Health) - Cetuximab appears to be effective for treating advanced cutaneous squamous cell carcinoma (cSCC), despite the rarity of oncogenic mutations, researchers from France report.

Cetuximab targets the epidermal growth factor receptor (EGFR), which is highly expressed in cSCC. There are no data concerning oncogenic mutations in cSCC related to response to cetuximab therapy.

Dr. Henri Montaudie from University Hospital of Nice and colleagues examined the relationship between somatic mutations of the HRAS, KRAS, NRAS, BRAF, and EGFR genes and the response to cetuximab in their retrospective study of 31 patients (median age, 86 years) with unresectable or metastatic cSCC.

There were only two mutated samples (6.5%), one harboring an NRAS point mutation and one with an HRAS mutation, according to the March 4th JAMA Dermatology online report.

The patient with the NRAS mutation showed a partial response to cetuximab, and the patient with the HRAS mutation showed a complete response.

Overall, the disease control rate at week 6 was 67.8%, with two patients achieving a complete response, 13 patients achieving a partial response, six patients having stable disease, and 10 patients having progressive disease.

Disease control rates were higher for patients with local disease (75.0%) than for patients with metastatic or lymph node disease (63.1%) and higher for previously untreated patients (100%) than for patients previously treated with surgery plus radiotherapy or chemotherapy (64.3%) or for patients previously treated with surgery alone (55.5%).

Median overall survival was 13 months, and median progression-free survival was 9 months. Forty-three percent of patients were alive at 18 months, and 29% were alive at 36 months.

“This study confirms the efficacy and acceptable tolerance of cetuximab as a single agent in advanced cSCC in the elderly population,” the authors conclude. “The incidence of HRAS, KRAS, NRAS, BRAF, and EGFR mutations is very low in cSCC and does not predict the response to cetuximab treatment. Therefore, looking for mutations in these genes is not useful before initiating cetuximab therapy for cSCC, but ultimately mutational data are needed to better define the genetic landscape of this disease.”

“Only two RAS mutated samples were identified; interestingly, those patients showed partial and complete responses,” write Dr. Edit B. Olasz and colleagues from Medical College of Wisconsin in Milwaukee, in an editorial. “Owing to the small sample size, this correlation should be confirmed on a larger cohort. Nevertheless, this study confirms that the search for mutations in the EGFR gene appears unnecessary before initiation of cetuximab for advanced cSCC.”

The data were presented at the annual meeting of the American Academy of Dermatology, held this year in Orlando, Florida.

Dr. Montaudie did not respond to a request for comments.

SOURCE: bit.ly/2lBms6n and bit.ly/2nbwB5N

JAMA Dermatol 2017.

(c) Copyright Thomson Reuters 2017. Click For Restrictions - https://about.reuters.com/fulllegal.asp