Breaking the myth

Katya Naidu - Mumbai

Erbitux the latest drug released by Merck KGaA slipped into controversy regarding the interpretation the results of a study. The drug is a monoclonal antibody targeting the epidermal growth factor receptor (EGFR). Erbitux has already been approved by the DCGI for both metastatic colorectal cancer patients as well as for squamous cell carcinoma of the head and neck.

In a Phase III study which was done for testing Erbitux for metastatic colorectal cancer (mCRC), it was reported upfront that the end point of overall survival was not met. However, the company explains that the reason why the end point was not met could be possibly because a considerable number of patients who were subjected to the standard progressed to the Erbitux combination.

The mix up

The EPIC study evaluated a combination of irinotecan plus Erbitux against irinotecan alone as a second line therapy for patients who failed first-line oxaliplatin based chemotherapy. The study recruited approximately 1,300 patients and were randomised to receive irinotecan plus Erbitux, or irinotecan alone. These patients were treated until disease progression and after that study treatment was stopped and treatment was given at the discretion of the physician.

The results showed that Erbitux plus irinotecan did not meet its primary efficacy endpoint of improving overall survival, compared to irinotecan alone. The primary endpoint could have been impacted by the fact that a considerable number of patients received the active treatment of Erbitux plus irinotecan after failing irinotecan therapy. An analysis of the final data, including secondary efficacy endpoints, as well as the impact of subsequent therapies on overall survival, is ongoing.

The positive side

In addition, the EPIC study also demonstrated that Erbitux strongly favoured the secondary endpoints of progression-free survival and response rate. "The observed differences in progression-free survival and response rate in EPIC, clearly demonstrate the activity of Erbitux in the treatment of metastatic colorectal cancer. It is well known that survival differences are difficult to achieve in diseases where multiple lines of active treatments are available," said Dr Wolfgang Wein, Senior Vice-President, Global Oncology Commercialization at Merck KGaA.

Claiming that Erbitux is one of the drugs which has very mature data, Sudheirr Dhillon, the Head of Oncology for Merck in India, clears that the general trend of the medicine shows positive response. "We are happy with the responses of patients in India (for both colorectal cancer and squamous cell carcinoma of the head and neck) in broader clinical usage."

There was yet another Phase III study which was conducted on Erbitux by the National Cancer Institute of Canada Clinical Trials Group in collaboration with the Australasian Gastro-Intestinal Trials Group. This evaluated Erbitux monotherapy versus best supportive care after failure of irinotecan, oxaliplatin, and fluoropyrimidines. "The results of the Erbitux monotherapy study are extremely encouraging as they reflect the power of Erbitux to attack cancer cells and significantly improve patient survival when all other conventional therapies have failed. This clearly differentiates Erbitux from other EGFR-targeting therapies that did not show a survival benefit in this setting," says Wein.

The company claims that it will continue to study Erbitux in both the adjuvant and metastatic colorectal cancer settings. Studies and trials are on for Erbitux in colorectal, non-small cell lung, pancreatic and head and neck cancers.