Treating Acquired Resistance to TKIs in NSCLC

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Rebiopsy is essential now that investigational third-generation agents like rociletinib and AZD9291 are available for patients with non-small cell lung cancer (NSCLC) who develop acquired resistance to either of the two frontline tyrosine kinase inhibitors (TKIs), erlotinib and afatinib. In general, 50% to 60% of patients with acquired resistance will have tumors that harbor the T790M mutation, making them candidates for a second- or third-generation TKI, Corey Langer, MD, states.

Tumors that are T790M—negative are more challenging to treat, states Langer. Mark Socinski, MD, explains that the use of third-generation TKIs, such as rociletinib and AZD9291, appear to be most effective in the T790M-positive population, but also have some limited activity in the T790M-negative subgroup.

One of the greatest breakthroughs in treating acquired resistance has been the use of the combination of afatinib and cetuximab, suggests Lecia Sequist, MD. The combination of afatinib and cetuximab elicits a response in 30% to 35% of patients. However, the side effects associated with the combination have limited its utilization.