According to today’s announcement by Roche, Tarceva (erlotinib), an oral lung cancer treatment, has been officially licensed as first-line monotherapy for the treatment of patients with advanced forms of non-small cell lung cancer (NSCLC) with a certain mutation, saving them from up-front chemotherapy.

The activating mutation is located in the EGFR (epidermal growth factor receptor) protein of NSCLC tumors. It can change the structure of the EGFR protein, increasing its activity, which in turn can lead to accelerated cell growth, cell division and development of metastases – when the cancer spreads to other parts of the body.

According to estimates, one in ten Western people and almost one in three Asian people with NSCLC have EGFR-activating mutations. Researchers believe that approximately three and a half thousand UK patients could benefit from this treatment annually.

The new license is based on data from several studies including two Phase III trials, EURTAC and OPTIMAL, that evaluated Western and Asian populations respectively. Both studies examined patients with an EGFR mutation and achieved similar results showing almost double the time, i.e. 9.2 months of patients in certain populations living without progression of their disease compared with 5.2 months to those receiving chemotherapy.

Dr. Liz Toy at the Royal Devon and Exeter Foundation NHS Trust said:

“Erlotinib has already been shown to significantly benefit lung cancer patients, regardless of their mutation status, after chemotherapy. This indication is exciting news for many lung cancer patients with this mutation as they could have an enhanced response using this targeted treatment without the need for immediate chemotherapy.”

Results from the EURTAC study showed that first-line treatment with Tarceva (erlotinib) almost doubled the time that people in a Western population lived with advanced NSCLC with an EGFR mutation (i.e. an average of 9.7 months) without their disease progressing compared with an average of 5.2 months in those who received chemotherapy. This represents a significant 63% reduction in risk of the disease worsening compared with standard chemotherapy (hazard ratio=0.37, p<0.0001). The results of the OPTIMAL study were similar in the Asian population, revealing that erlotinib almost tripled the average time people in China with this distinct form of lung cancer lived, i.e. 13.7 months without their disease getting worse compared with 4.6 months for those receiving chemotherapy (hazard ratio=0.16, p<0.0001). Over twice as many patients (83 %) receiving erlotinib experienced tumor shrinkage compared with 36% of those receiving chemotherapy (p<0.0001). Rash and diarrhea were reported as the most common side effects. The studies’ safety profiles were similar to those reported in previous trials. Erlotinib is a TKI (Tyrosine Kinase Inhibitor), a modern class of medication and much more specifically targeted than existing chemotherapy drugs. Erlotinib does not have the side effects commonly linked to chemotherapy, such as nausea, vomiting, fever, hair loss or infection. Gefitinib is the only other licensed medication in this class.

For treatment in advanced or metastatic NSCLC irrespective of a patient’s EGFR status, erlotinib is already approved in the UK as a maintenance therapy directly after initial chemotherapy and as a second-line therapy in progressed diseases that already received one course of chemotherapy. In the second line setting, erlotinib has increased overall survival by 6.7 months compared with 4.7 months of best supportive care alone.

With over 39,000 new cases of lung cancer diagnosed in Britain each year, it is one of the biggest cancer killers.

Only 25% of lung cancer patients survive one year and just 8% survive for five years. It kills 3,000 more women annually compared with breast cancer and claims more male cancer deaths than prostate, pancreatic, kidney and stomach cancer combined.

Approximately 80% of lung cancers in the UK are caused by NSCLC, and despite the fact that this is the UK’s biggest cancer killer, lung cancer receives less than 4% of government research funding, compared to around 20% for breast, 12% for colorectal and 8% for prostate cancer.

EGFR is a protein that expands across the cell membrane. Epidermal growth factor (EGF) binds to the part of the EGFR protein that sits on the outside of the cell. The binding causes activation of the EGFR protein which in turn triggers a complex signaling cascade within the cell that leads to events including accelerated cell growth, cell division and development of metastases (tumor growth and spread to other parts of the body). Mutations in the EGFR gene, that change the structure of the EGFR proteins can lead to increased activity which can be found in some NSCLC tumors.

Erlotinib is a non-chemotherapy drug for the treatment of advanced or metastatic NSCLC and is administered orally once a day. It successfully inhibits EGFR, a protein involved in the growth and development of cancers. Erlotinib is a registered trademark of OSI Pharmaceuticals, LLC, a member of the Astellas global group of companies.

Written by Petra Rattue