Pivotal phase III results of afatinib as first-line treatment in patients with advanced adenocarcinoma of the lung harboring EGFR-activating mutations
LUX-Lung 3 is the largest prospective study in first-line EGFR mutation positive, advanced, metastatic NSCLC
- Date : 06 Jun 2012
- Topic : Lung and other thoracic tumours
Highly anticipated results from LUX-Lung 3, the pivotal phase III randomised, open-label, lung cancer trial investigating the ErbB family blocker afatinib, in patients with EGFR mutations, are presented at the 48th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago (1 - 5 June 2012). LUX-Lung 3, which compares afatinib to standard platinum based chemotherapy, is the largest phase III trial in first-line EGFR mutation positive, advanced, metastatic non-small cell lung cancer (NSCLC) patients. LUX-Lung 3 is also the first study using pemetrexed/cisplatin as a comparator.
Afatinib is a selective, orally bioavailable, irreversible ErbB family blocker of EGFR (ErbB1), HER2 (ErbB2), and ErbB4. This global study investigated the efficacy and safety of afatinib compared with pemetrexed/cisplatin. Primary endpoint was progression-free survival (PFS) by central independent review.
Following central testing for EGFR mutations by companion diagnostic kit, 345 patients with stage IIIB/IV NSCLC, performance status 0–1, and chemo-naive were randomised 2:1 to daily afatinib or intravenous pemetrexed/cisplatin. Baseline characteristics were balanced in both arms regarding median age, sex, ethnicity, smoking status, and presence of mutations.
Afatinib may be considered as a novel, clinically relevant, first-line treatment option
Treatment with afatinib led to a significantly prolonged PFS (median 11.1 vs 6.9 months, p=0.0004). In 308 patients with common mutations (Del19/L858R), median PFS was 13.6 vs 6.9 months, p<0.0001. Objective response rate was significantly higher with afatinib (56% vs 23%, p<0.0001). Significant delay in time to deterioration of cancer-related symptoms of cough and dyspnea was seen with afatinib vs pemetrexed/cisplatin. Most common drug-related adverse events were diarrhoea (95%), rash (62%) and paronychia (57%) with afatinib, and nausea (66%), decreased appetite (53%) and vomiting (42%) with pemetrexed/cisplatin.
Drug-related adverse events led to discontinuation in 8% (afatinib; 1% due to diarrhoea) and 12% of patients in pemetrexed/cisplatin arm.
The researchers concluded that LUX-Lung 3 is the largest prospective trial in EGFR mutation positive lung cancer and the first study using pemetrexed/cisplatin as a comparator. Treatment with afatinib significantly prolonged progression-free survival compared to pemetrexed/cisplatin, with significant improvements in secondary endpoints.
Adverse events with afatinib were manageable, with a low discontinuation rate. With 4.2 months improvement in progression-free survival in the overall study population and 6.7 months in patients with common mutations, afatinib may represent a clinically relevant first-line treatment option.
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