Combining afatinib and cetuximab produced positive clinical responses in lung cancer patients with epidermal growth factor receptor (EGFR) mutations that had developed resistance to EGFR inhibitors erlotinib and gefitinib. These are the results of a Phase 1 clinical trial published in the journal of the American Association for Cancer Research Cancer Discovery.
As explained by first author of the study Yelena Janjigian, an assistant attending physician at Memorial Sloan Kettering Cancer Center in New York, although erlotinib and gefitinib therapies leads to “dramatic tumor regression,” while improving survival for patients with EGFR-mutant lung adenocarcinoma, these cancers acquire resistance to these drugs, causing the disease to progress.
As part of the study, researchers enrolled 201 patients in the clinical trial, of which 126 were provided post-acquired-resistance tumor samples for profiling EGFR T790M mutations. Among the patients, the median progression-free survival was 4.7 months, while the median duration of confirmed objective response was 5.7 months. Researchers report that therapy-related adverse events were registered in 44% of the patients. Among the 37 patients who had a confirmed objective response, 22 had their tumors shrink by 50% or more.
As the clinical trial was concluded, the team found that the afatinib–cetuximab combo demonstrated robust clinical activity and a manageable safety profile in EGFR-mutant lung cancers with acquired resistance to gefitinib or erlotinib, both with and without T790M mutations, warranting further investigation.
These results led researchers to conclude that a significant proportion of tumors in patients with acquired resistance to gefitinib/erlotinib remain dependent on EGFR signaling for survival.
Although larger, randomized trials are needed to confirm the results, the afatinib-cetuximab combo seems to be the answer for these patients, as the study showed that this combination results in “durable and robust clinical responses in the setting of acquired resistance,” Janjigian said.
Furthermore, she added, the treatment combination “benefited patients whether or not their cancer had acquired resistance to erlotinib or gefitinb.”
Of the 201 patients enrolled in the clinical trial by Janjigian and colleagues, 126 received the maximum-tolerated dose of combined afatinib and cetuximab. All these patients had EGFR-mutant lung cancer that had progressed during treatment with erlotinib or gefitinib, and 37 of them had a confirmed objective response to afatinib plus cetuximab. The overall median duration of the responses was 5.7 months.