Results from a Phase III international trial show that initial single-agent oral therapy with the targeted drug afatinib prolongs progression-free survival (PFS) in patients with advanced lung adenocarcinomas that harbor epidermal growth factor receptor (EGFR, also known as ErbB1) mutations, compared with standard chemotherapy.

Researchers found that afatinib was particularly beneficial – leading to a doubling of PFS – in the majority of patients who had one of two common types of EGFR mutations, deletion 19 or L858R.

These two mutations together account for approximately 90 percent of all EGFR mutations.

This is the first time findings from this trial – LUX-lung 3 – have been presented, and they are of particular interest because researchers compared afatinib with a relatively new first-line regimen for advanced, previously untreated lung adenocarcinoma: combined pemetrexed and cisplatin chemotherapy.

This form of disease is a subtype of non-small cell lung cancer. EGFR mutated, or driven, lung adenocarcinoma is often clinically associated with patients who have never smoked and patients of Asian descent. In the United States, it is estimated that over 18,000 patients will be diagnosed with lung adenocarcinoma harboring EGFR activating mutations each year.

The EGFR pathway facilitates cancer cell growth, survival and spread. Laboratory studies have shown that afatinib chemically blocks this pathway more thoroughly and permanently than current EGFR-targeted treatments, such as gefitinib and erlotinib. Additionally, afatinib blocks the broader ErbB family of receptors that are associated with the EGFR pathway, including HER2 (ErbB2) and HER4 (ErbB4), and can inactivate further cancer cell pathways.

“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 James Chih-Hsin Yang, MD, PhD, a Professor at the National Taiwan University and the principle investigator of this multi-national study. “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 doctors’ office than standard chemotherapy – another important quality of life advantage.”

In this study, researchers randomised 345 patients to afatinib or standard combination chemotherapy treatment, given intravenously.

All participants had EGFR mutations that were identified through central testing, and the imaging scans were independently reviewed to evaluate treatment outcomes. After a median follow-up of 8 months, they found that afatinib delayed disease progression by more than 4 months over standard therapy (PFS: 11.1 vs. 6.9 months).

Among the 308 patients with either deletion 19 or L858R, PFS was prolonged even further (13.6 vs. 6.9 months). Researchers noted that patients treated with afatinib were also slower to experience worsening of common lung cancer-related symptoms, including cough and dyspnea (shortness of breath) and showed a better quality of life when compared with patients receiving chemotherapy.

Side effects with afatinib were comparable to those of other EGFR-targeting therapies. Overall survival data are expected in about two years, according to Dr. Yang. 

Source: ASCO