Jack West, MD: Use of TKI Therapy in Patients with EGRF Exon 19 Deletion NSCLC

What efficacy data support the use of this TKI therapy in a patient such as Ingrid with EGRF exon 19 deletion NSCLC?

Over the past 6 years or so, we have obtained evidence from multiple studies that patients with an activatingEGFRmutation, either exon 19 deletion or an L858R substitution on exon 21, do significantly better when their first-line therapy is anEGFR) TKI. Over the years, three different [TKIs] have been studied: gefitinib, erlotinib, and, most recently, afatinib. They produce very similar results and this consistently means a marked improvement in response rate and a much higher progression-free survival (PFS) in recipients of anEGFRTKI compared with conventional chemotherapy in this first-line setting.

However, we’ve also seen in the afatinib trials, and specifically those called LUX-Lung 3 and LUX-Lung 6, that patients, particularly with an exon 19 deletion, have a survival benefit compared with the patients that received first-line chemotherapy. In fact, that hasn’t been seen with otherEGFRtyrosine kinases before. It’s possible that these results might be seen in larger studies with the otherEGFRinhibitors; it’s fair to say that these agents have not been compared head to head. But at present, we have evidence of a survival benefit in this particular subset of patients. Because of that, it makes afatinib a particularly compelling choice for this kind of patient.

CASE 1: mNSCLC

Ingrid C. is a 62-year-old corporate accountant from San Antonio, Texas. Her medical history is notable for depression, which is being treated with an SSRI, and she has no history of smoking.

At the start of busy tax season, she presents to her PCP with back and chest pain, a persistent cough, and intermittent dyspnea.

Her cardiac workup is negative, and her PCP orders a chest x-ray, which shows bilateral lung nodules and a large upper right lung mass with pleural effusion; she is referred for a follow-up CT scan.

The CT confirms the presence of multiple lung nodules and additional lesions in the thoracic vertebra; she is referred for further diagnostics.

Core biopsy of her lung mass shows adenocarcinoma stage IV; mutational testing showsEGFRdel 19.

Her performance status was 1.0 at diagnosis.

Ingrid has a family vacation in Tuscany planned for next year, and hopes to be able to keep her travel plans; her oncologist initiates her on afatinib 40 mg daily.

She returns to her oncologist in 2 weeks with persistent diarrhea (>5 stools/d) that has not responded to antidiarrheal medications, which were suggested by the nursing team, and her normal work day is being affected.

Her oncologist reduces her afatinib dose to 30 mg/day, and she continues therapy.

Nine weeks after initiating therapy, she reports to the nursing team symptoms of redness and swelling in her fingers and fingernails, and management strategies are recommended.

At her next follow-up 2 months later, her CT scan shows the right lung mass to be stable, with no new lesions. She has improved symptomatically.

Her diarrhea has improved sufficiently to allow her to resume her normal work load; her paronychia has been effectively managed with vinegar soaking and topical antibiotics.