Non-Small-Cell Lung Cancer (NSCLC) accounts for almost 80% of lung cancer cases. Late diagnosis limits therapeutic options and, because of the side effects of conventional treatment, patients with advanced lung cancer often choose not to be treated. Furthermore, the impact of new chemotherapy regimens on survival rates has been modest at best.
Tarceva®, a new 'molecular-targeted' therapy, is one of a new generation of anti-cancer agents. It interferes with tumour growth and development by blocking the activity of the enzyme Tyrosine Kinase (TK).
Tarceva acts specifically on the TK linked to the Human Epidermal Growth Factor Receptor 1 (HER-1/EGFR). Activation of this receptor initiates a cascade of biochemical signalling pathways, leading to increased cellular proliferation, new blood vessel development and metastasis. Blocking the TK linked to this receptor inhibits these processes and in tumour cells this inhibition reduces or reverses tumour growth and development.
By targeting a biochemical pathway specifically linked to tumour cell growth, Tarceva suppresses disease progression with minimal adverse consequences for the patient.
The National Cancer Institute of Canada Clinical Trials Group recently published clinical evidence for the validity of this approach in The New England Journal of Medicine. The institute conducted a phase III trial to determine whether Tarceva prolongs survival in NSCLC patients whose illness has progressed during first-line chemotherapy.
Some 731 patients were randomised (2:1) to receive either oral Tarceva (150mg/day) or placebo. The primary endpoint of the study was overall survival. Secondary endpoints included progression-free survival, overall response rate, duration of response, toxic effects and quality of life.
The study met its primary endpoint; patients receiving Tarceva had a median overall survival of 6.7 months, compared with 4.7 months in the placebo group, a statistically significant and clinically relevant increase. Patients given Tarceva also had longer progression-free survival than those given placebo (2.2 months vs 1.8 months).
Importantly, Tarceva delayed progression of disease-related symptoms (cough, pain and breathlessness), resulting in a significant improvement in patients' quality of life.
As an additional benefit, Tarceva has fewer adverse effects than conventional chemotherapy. The side effects commonly seen with chemotherapy (anaemia, fatigue and alopecia) can severely compromise patients' quality of life. In contrast, Tarceva's most common side effects (rash and diarrhoea) are usually mild to moderate in severity and are easily manageable.
Commenting on the study's favourable results, principal investigator Dr Frances Shepherd says: "This phase III study represents an important medical advance in the field of lung cancer research. In addition to being the first noncytotoxic treatment to improve survival in advanced lung cancer, this study showed that Tarceva extended survival across most subsets of patient populations in the trial."
This pivotal phase III trial demonstrates that Tarceva is an effective and well-tolerated treatment for NSCLC.
Tarceva is the first drug of its type to gain approval in the EU for the treatment of patients with advanced NSCLC who have failed previous chemotherapy treatments.
Promisingly, Tarceva also shows activity in other indications, including ovarian cancer, head and neck squamous cell cancer and renal cell cancer in combination with another new targeted agent, Avastin®. Results will soon be available from NSCLC studies examining combined Tarceva and Avastin treatment.
If the potential of these new therapies is realised, we may be witnessing the dawn of a new era of anti-cancer therapies that selectively target the underlying mechanisms of tumour development, allowing patients to live better, longer lives.