Using a pharmacogenetic strategy to home in on a molecularly defined non-small cell lung cancer patient population, researchers have shown in a clinical trial that the investigational EGFR inhibitor afatinib significantly prolongs survival in patients with EGFR-mutated tumors.
Researchers from Boehringer Ingelheim and elsewhere presented data at the American Society of Clinical Oncology’s annual meeting this week on the LUX-Lung 3 trial, which they heralded as the “largest and most robust” trial performed to date in the EGFR-mutation positive NSCLC population. Sponsor Boehringer Ingelheim will likely seek approval for afatinib as a first-line therapy for this subset of lung cancer patients.
The data, presented by lead study author James Chih-Hsin Yang of National Taiwan University Hospital, also showed that patients who harbor two of the most common EGFR mutations respond especially well to afatinib.
In the LUX-Lung 3 trial, study investigators enrolled 345 patients from 130 sites in 25 countries. Patients with Stage IIIB/IV adenocarcinoma and EGFR-positive tumors were randomized to receive either afatinib or the most effective chemotherapy regimen containing cisplatin and pemetrexed. The primary endpoint of the study was independent reviewer-assessed progression-free survival, or the period of time patients were alive without their disease advancing. Secondary endpoints included overall survival, disease control rate, tumor shrinkage, patient-reported outcomes, and safety. Study participants were previously untreated for advanced NSCLC.
The data from LUX-Lung 3 showed that patients receiving afatinib lived for a median of 11.1 months without their cancer progressing, while patients receiving cisplatin/pemetrexed lived for a median of 6.9 months. The overall survival data in the study are not yet mature.
After 12 months, “47 percent of patients in the study who received afatinib had not progressed, [while] 22 percent of people who received chemotherapy have not progressed,” Yang said. “With this simple measurement, you can tell that the patients who received afatinib enjoyed a longer progression-free survival time compared with chemotherapy.”
Patients on the afatinib arm had around a 40 percent less chance of dying than patients on the chemotherapy arm. According to an assessment by independent reviewers, tumors shrank in 56 percent of patients following treatment with afatinib, compared to 22.6 percent of patients in the chemo arm.
Between 30 percent and 40 percent of Asian adenocarcinoma patients and between 5 percent and 15 percent of Caucasian adenocarcinoma patients harbor EGFR mutations. Although this molecularly targeted population is small, the incidence of NSCLC is so high that many patients stand to potentially benefit from a personalized medicine treatment approach, Yang said during his presentation.
Throughout the world, there are approximately 1.6 million new cases of lung cancer each year, 85 percent of which are the non-small cell type. For the majority of lung cancer patients, their diagnosis comes too late for surgery to be an option. Chemotherapy regimens have shown to prolong survival for about one year. In the US, 15 percent of lung cancer patients survive for five years after diagnosis.
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