New irreversible ErbB receptor blocker seems more potent than other therapies
August 2012 Vol 5, No 5, Special Issue ASCO 2012 Payers' Perspective - Lung Cancer
Wayne Kuznar

Chicago, IL—Based on the results of a phase 3 study, patients with advanced lung adenocarcinomas that harbor epidermal growth factor receptor (EGFR) mutations experience extended progression-free survival (PFS) when treated with the investigational ErbB receptor family blocker afatinib as single-agent therapy compared with standard chemotherapy.

The international trial, known as LUX-lung 3, showed that the use of afatinib, an ErbB family blocker of epidermal growth factor, HER2, and ErbB4 receptors, doubled PFS in most patients who had 1 of the 2 prevalent EGFR mutation types, deletion 19 or L858R.

“With 4.2 months of PFS improvement in the overall population and 6.7 months in patients with common mutations, afatinib is a clinically relevant first-line treatment option,” said lead investigator James Chih-Hsin Yang, MD, PhD, Professor at National Taiwan University, Taipei, at ASCO 2012.

The randomized trial, the largest of its kind to evaluate EGFR mutation–positive lung cancer, involved the evaluation of afatinib, comparing it against a recent first-line regimen option for advanced but not yet treated lung adenocarcinoma—combined pemetrexed and cisplatin chemotherapy. Unlike reversible EGFR (ErbB1) tyrosine kinase inhibitors, afatinib irreversibly blocks the entire ErbB family of receptors.

“By more broadly and effectively blocking the molecular pathways that facilitate the growth of these cancers, afatinib appears to be more potent than other therapies,” said Dr Yang. “This new treatment could not only help patients live a longer period of time without further cancer progression, but because it’s given orally, it may also require fewer visits to the doctor’s office than standard chemo­therapy—another important quality of life advantage.”

In the study, 345 patients were randomized to oral afatinib or standard combination intravenous chemotherapy (pemetrexed and cisplatin) in a 2:1 ratio. Every patient had an EGFR mutation. Baseline traits were similar in the 2 study arms: 65% of patients were female, 72% were Asian, 68% never smoked, and the median age was 61 years.

After a median follow-up of 8 months, afatinib delayed disease progression by more than 4 months over standard therapy (PFS, 11.1 months vs 6.9 months, respectively). PFS was delayed further (13.6 months vs 6.9 months, respectively) for 308 patients with the more prevalent EGFR mutations—deletion 19 or L858R.

Common symptoms of lung cancer, such as cough and dyspnea, did not occur as quickly (40% delay) in patients taking afatinib compared with those receiving chemotherapy, said Dr Yang.

He noted that adverse events were “as expected” with EGFR inhibition, consistent with earlier studies, and were manageable, reversible, and predictable.

Adverse events related to the drugs included diarrhea (95%), rash/acne (62%), and paronychia (57%) with afatinib, and nausea (66%), reduced appetite (53%), and vomiting (42%) with combination chemotherapy. These adverse events led to an 8% discontinuation rate among study patients.

Patients who received afatinib experienced greater tumor shrinkage than those who received the standard chemotherapy, according to Dr Yang.

The response rate for people who received afatinib was 56%, and in those assigned to chemotherapy it was 23%.

On a questionnaire to assess quality of life, patients randomized to afatinib rated their quality of life in overall health status higher than those receiving chemotherapy.—WK

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Last modified: August 30, 2012
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