Dr Rodriguez on TKIs in Lung Cancers With Uncommon EGFR Mutations

Estelamari Rodriguez, MD, MPH, associate director, Community Outreach – Thoracic Oncology, Sylvester Comprehensive Cancer Center, discusses the benefits of the TKIs afatinib (Gilotrif) and osimertinib (Tagrisso) in patients with lung cancer with uncommon EGFR mutations.

In patients with lung cancer, EGFR mutations can fall into several categories. Sensitizing EGFR mutations and EGFR exon 20 insertion mutations are 2 distinct groups, and all other EGFR mutations are atypical, or uncommon, EGFR mutations, Rodriguez says. Historically, patients with lung cancer with uncommon EGFR mutations have had unfavorable outcomes with first- and second-generation TKIs, Rodriguez notes.

However, data support the use of the TKI afatinib in patients with lung cancer with uncommon EGFR mutations, and in 2018, the agent was approved by the FDA in this population based on findings from the phase 2 LUX-Lung 2 (NCT00525148) and phase 3 LUX-Lung 3 (NCT00949650) and LUX-Lung 6 (NCT01121393) trials. Since afatinib is an irreversible EGFR receptor inhibitor, it has activity against several uncommon EGFR mutations, Rodriguez explains. Although this agent causes more rash and diarrhea than other TKIs, these are manageable with dose adjustments and supportive care.

Additionally, osimertinib in under global investigation as a first-line therapy for patients with lung cancer with uncommon EGFR mutations. Osimertinib targets EGFR resistance mutations such as T790M, with a high degree of mutant receptor activity and fewer adverse effects than other TKIs, Rodriguez says.

Targeted therapies are optimal frontline treatment options for patients with molecularly driven cancers, such as those with EGFR-mutant lung cancers, in whom chemotherapy can often be reserved for later lines, Rodriguez emphasizes. Another benefit of afatinib and osimertinib is their ability to penetrate the central nervous system barrier, which is a common site of progression in patients with lung cancers with uncommon EGFR mutations, Rodriguez notes. Afatinib is approved by the FDA in this population, and data support the use of osimertinib in these patients as well, Rodriguez concludes.