LUX-Lung 7 Trials Shows Afatinib Achieves Better Response Than Gefitinib in Patients With EGFR-mutated Lung Cancer
SINGAPORE—Advanced lung cancer with epidermal growth factor receptor (EGFR)-activating mutations appear to respond more to firstline treatment with afatinib than with gefitinib, researchers reported at the European Society for Medical Oncology (EMSO) Asia 2015 Congress.
In the global, randomized, open-label phase IIb LUX-Lung 7 (LL7) trial, efficacy was significantly improved with afatinib vs. gefitinib across a range of clinically relevant end points, such as progression-free survival, time-to-treatment failure, and objective response rate.
NSCLC is the most common type of lung cancer. Among cases of NSCLC, activating EGFR gene mutations are more frequently observed in nonsmokers and women. They also occur in 50% of Asian patients but only 10% of non-Asian patients.
Afatinib and gefitinib are targeted agents that block key pathways involved in tumor growth and spread. Both are approved for treatment-naïve patients, based on phase III trials indicating their superiority to chemotherapy. Unlike gefitinib, a first-generation EGFR inhibitor, afatinib, an irreversible ErbB family blocker, is suggested to be active in prolonging tumor response and delaying disease progression.
"First-line afatinib treatment significantly reduced the risk of lung cancer progression by 27% vs. gefitinib," said Keunchil Park, MD, PhD, head of the Division of Hematology/Oncology at Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, and lead author of the study. "Interestingly, the improvement in progression-free survival became more pronounced over time with a significantly higher proportion of patients alive and progression-free at 18 months (27% vs 15%; P=.018) and 24 months (18% vs 8%; P=.018), showing a greater long-term benefit of using the irreversible ErbB family blocker afatinib."
Of 319 patients randomly allocated to each of the 2 arms, a significantly higher proportion responded to afatinib vs. gefinitib (70.0% vs. 56.0%, respectively; P=.008) for a median duration of 10.1 months (95% CI, 7.82-11.10) and 8.4 months (95% CI, 7.36-10.94), respectively.
"Overall, the frequency of severe adverse events was similar in both arms with slightly different toxicity profiles. The adverse events observed with both treatments were predictable and manageable, leading to an equally low rate of treatment discontinuation in both arms (6.3%)," said Park.
ESMO spokesperson Martin Reck, MD, PhD, chief oncology physician at the Department of Thoracic Oncology at the Hospital Grosshansdorf, Germany, who was not involved in the study, cautioned that “tolerability also plays a determining role in the selection and dosing of a tyrosine kinase inhibitor. The tolerability profiles between gefitinib and afatinib are different and the selection of the therapy will still be based on the individual clinical decision."
The primary analysis of overall survival data is planned in 2016 and will provide further responses.