NEW YORK – A real-world observational study has shown that treatment with afatinib (Boehringer Ingelheim's Gilotrif) followed by osimertinib (AstraZeneca's Tagrisso) resulted in prolonged survival of almost four years for non-small cell lung cancer patients with EGFR Del19 and T790M mutations.
A number of first-, second-, and third-generation EGFR inhibitors are available for the treatment of EGFR mutation-positive NSCLC patients, and randomized studies have shown that second- and third-generation drugs confer better progression-free survival than first-generation drugs. However, there is currently no head-to-head comparison of the newer second- or third-generation agents — afatinib, dacomitinib (Pfizer's Vizimpro), and osimertinib — and it is unclear how to sequence these drugs for optimal survival.
In a study published last week in Future Oncology, researchers led by Tanja Cufer from the University of Ljubljana in Slovenia wrote that osimertinib has shown “impressive activity” as a second-line treatment for patients with T790M-positive tumors. Acquiring the T790M mutation is the main way EGFR mutation-positive NSCLC patients become resistant to first- and second-generation targeted EGFR treatments. Based on data from existing real-world data cohorts, the researchers decided to investigate survival outcomes of patients who receive osimertinib as a second-line option after failing a second-generation agent such as afatinib.
"It's important to consider sequencing of therapies to provide patients with as many future treatment options [as possible] given that many of them with this type of lung cancer eventually acquire resistance to EGFR tyrosine kinase inhibitors," Balazs Halmos, chief of thoracic/head and neck oncology at Montefiore Medical Center and a study author, said in a statement.
The GioTag study, financially supported by Boehringer, involved around 200 EGFR tyrosine kinase inhibitor-naive NSCLC patients, who were first treated with afatinib until they developed T790M-positive acquired resistance and then received second-line osimertinib. Earlier data from the trial indicated that this sequential treatment strategy had promising overall survival of around two years and 2.5 years, but the data was immature.
The real-world study was conducted across 10 countries: the US, Taiwan, Spain, Slovenia, Singapore, Japan, Italy, Israel, Canada, and Austria. Data were drawn from manual medical chart reviews or electronic health records from Cardinal Health.
EHR data from a subset of 94 patients with T790M acquired resistance enabled the researchers to conduct the latest interim analysis rapidly. After a median follow up of 30 months, median survival was nearly three and a half years, with 80 percent of patients alive at two years. Patients with Del19 mutation-positive NSCLC seemed to benefit particularly well, experiencing a median overall survival of 45.7 months, with 82 percent alive at two years.
Median time to treatment failure (TTF), the primary study outcome, for sequential afatinib and osimertinib was 28.1 months in the overall cohort and 30.6 months in those with Del19-positive tumors. The median TTF on osimertinib was 15.6 months in the overall study population and 16.4 months in those with Del19-positive tumors.
"The continued clinical development of new EGFR tyrosine kinase inhibitors provides additional treatment options for patients with EGFR mutation-positive NSCLC and raises questions about their optimal sequence," Victoria Zazulina, global head of oncology at Boehringer, said in a statement.
However, since no established targeted treatments are available after patients fail osimertinib, Zazulina noted, there is an argument for reserving osimertinib for second-line use after second-generation EGFR TKIs. "Real-world data from the GioTag study supports the argument for sequential use of afatinib and osimertinib for patients with EGFR mutation-positive NSCLC who are Del19-positive," she said in a statement.
The final analysis from GioTag, slated for early 2020, will include additional data from Asian and European countries. Because this is a retrospective observational study, the researchers noted, prospective data are required to investigate which sequential treatment strategies impart the best overall survival advantage in EGFR mutation-positive NSCLC patients.