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Afatinib plus cetuximab shows promise for EGFR-mutated lung cancer
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Afatinib plus cetuximab demonstrated clinical activity and a manageable safety profile in patients with EGFR-mutant lung cancers with acquired resistance to gefitinib or erlotinib, both with and without T790M mutations, according to findings in an early-phase trial.
“Treatment with erlotinib and gefitinib leads to dramatic tumor regression and has improved survival for patients with EGFR-mutant lung adenocarcinoma,” Yelena Y. Janjigian, MD, assistant attending physician at Memorial Sloan Kettering Cancer Center, said in a press release. “Unfortunately, these cancers invariably acquire resistance to these drugs and the patient’s disease progresses. There are currently no effective therapies for patients in this situation.”
Yelena Y. Janjigian
Based on preclinical observation, Janjigian and colleagues sought to determine the safety and preliminary efficacy of combined EGFR blockade with afatinib (Gilotrif, Boehringer Ingelheim) and cetuximab (Erbitux, Eli Lilly) in patients with EGFR-mutant tumors and acquired resistance to erlotinib (Tarceva, Genentech) or gefitinib (Iressa, AstraZeneca).
The researchers enrolled 126 patients with EGFR-mutated lung cancer to receive the maximum tolerated dose of afatinib (40 mg oral daily) plus cetuximab (500 mg/m2 intravenously every 2 weeks).
According to study results, objective response rate (overall 29%) was comparable in T790M-positive (32%) and T790M-negative tumors (25%; P=.341). Median PFS was 4.7 months (95% CI, 4.3-6.4), and the overall median duration of the responses was 5.7 months (range, 1.8-24.4).
“Our study shows that a combination of afatinib and cetuximab can yield durable and robust clinical responses in the setting of acquired resistance, although larger, randomized trials are needed to confirm the results,” Janjigian said. “Importantly, the afatinib/cetuximab combination benefited patients whether or not their cancer had acquired resistance to erlotinib or gefitinib as a result of a secondary mutation in EGFR called T790M.”
In addition, among patients who achieved a confirmed objective response, 22 had their tumors shrink by 50% or more. The researchers noted that this level of tumor shrinkage is clinically significant because it results in regression of cancer-related symptoms and improvement in the patient’s quality of life.
“We were pleased to observe that EGFR T790M-positive and T790M-negative tumors responded,” Janjigian said. “This is important because there are third-generation EGFR inhibitors under development that can target EGFR T790M, but it is not likely that these will benefit patients with EGFR T790M-negative disease.”
Disclosure: The researchers reported funding from Bayer, Boehringer Ingelheim, Eli Lily and Genentech.
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