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Mutated lung cancer responds to targeted therapy

By DR. V. UPENDER RAO
Published January 29, 2007

Lung cancer is a devastating disease. Just one decade ago, it was not uncommon for physicians to tell patients that they may not live to see the anniversary of their diagnosis.

In the past 10 years, small but incremental and cumulative improvements have surfaced, mostly related to newer chemotherapy drugs, better management of side effects and improved surgical and radiation techniques.

Chemotherapy for early stage lung cancer after surgical resection was shown to improve survival. Clinical trials in the United States and Canada established the superiority of palliative chemotherapy for advanced disease as compared with supportive care alone, both in terms of clinical improvement of symptoms and cost.

The development of targeted drugs has yielded even more interesting results. Geftinib and Tarceva are two such drugs that target the Epidermal Growth Factor Receptor.

Patients whose tumors harbor mutations in the EGFR often respond impressively and dramatically. A few of the several targeted drugs that are being successfully used in oncology practice are Rituxan, Herceptin, Gleevec and Cetaxumab, against lymphoma, breast cancer, chronic myelogenous leukemia and colon cancer, respectively.

In this month's issue of The Oncologist, researchers from Harvard Medical School, Massachusetts General Hospital and Dana Farber Cancer Institute performed a retrospective cohort study of 278 patients with non-small cell lung cancer who were referred for EGFR testing over a 10-month period. They performed DNA sequence analysis exons 18 through 24 of the EGFR and analyzed their response to targeted therapy.

They found these mutations in 24 percent of the tested patients. A minimal smoking history was the strongest indicator of presence of a mutation. Each year of cigarette smoking corresponded to a 5 percent decrease in finding these favorable mutations.

Among patients with advanced unresectable cancer, the presence of a mutation strongly corresponded with response to targeted therapy, but not to chemotherapy. Mutation-positive patients achieved a median survival of 3.6 years as compared with 1.6 years for mutation-negative patients.

Significant changes in the management of non-small cell lung cancer have occurred in the past 10 years. Physicians have the opportunity for treating early-stage patients with chemotherapy after surgery and late-stage patients with palliative chemotherapy and radiation therapy.

Patients who are nonsmokers or those who have minimal smoking history should undergo EGFR mutation analysis since they may respond favorably to targeted therapy even with advanced disease.

V. Upender Rao, M.D., FACP, practices at the Cancer and Blood Disease Center in Lecanto.

[Last modified January 28, 2007, 23:04:32]