New guidelines for non-small cell lung cancer (NSCLC) recommend testing for epidermal growth factor receptor (EGRF) mutations as a part of routine care for patients diagnosed with non-small cell lung cancer (NSCLC), according to a presentation at the 2016 National Comprehensive Cancer Network Annual Conference (March 31—April 2, 2016; Hollywood, FL).
Rogerio Lilenbaum, MD, chief medical officer of Smilow Cancer Hospital at Yale-New Haven (New Haven CT) delivered the presentation, where he discussed new developments in first-line treatment of EGFR-mutated NSCLC. Dr Lilenbaum began by stating that access to the therapies gefitinib, erlotinib, and afatinib can improve the survival of patient populations with EGFR mutations compared with those who present with wild-type NSCLC or those who have EGRF mutations and are not treated with targeted therapies.
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Currently, patients are only tested for EGFR if they are have a high probability of having the mutation, but Dr Lilenbaum argued that molecular testing should now be more widely implemented as the standard when initiating care.
In randomized trials with EGFR+ patients with NSCLC, gefitinib, erlotinib, and afatinib—all tyrosine-kinase inhibitors (TKIs)—consistently showed improved patient outcomes of overall response rate (ORR), and progression-free survival (PFS) compared with chemotherapy. However, Dr Lilenbaum continued, treatment with TKIs should only begin once EGFR results have been received.
In comparisons of the TKIs as first-line treatments, afatinib showed superior rates of ORR, PFS, and time to failure compared with gefitinib, while another study found that the combination of bevacizumab and erlotinib was associated with significantly longer PFS compared with erlotinib alone in patients with EGFR+ mutations.
Still, disease progression was noted in most patients, indicating an acquired resistance to the TKIs over time. In another session, Leora Horn, MD, MSc Vanderbilt Ingram Cancer Center (Nashville TN), presented on how the T790M mutation could be a mechanism by which NSCLC cells acquire a resistance to TKIs.
Patients with systemic disease progression often have new lesions and multiple disease sites, said Dr Horn. These patients are ones that need to be switched off TKIs. They can be continued in patients who progress only in the central nervous system, but those lesions should also be radiated. Switching to a third- or fourth-generation TKI can also prove effective.
Before switching therapies, though, patients should be evaluated for T790M mutation through a biopsy or serum-based test when biopsy is not reasonable. Osimertinib is one therapy approved by the US Food and Drug Administration that has shown improved PFS in patients with EGFR+ NSCLC who progress while on two lines of prior therapy, one being a TKI.
Therefore, the new guidelines recommend osimertinib or the continuation of erlotinib, afatinib, or gefitinib for asymptomatic patients with NSCLC who are EGFR-positive. For symptomatic patients, subsequent therapy based on how the disease progresses is recommended.
