Corey J. Langer, 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?

The therapeutic landscape has clearly changed, as her case definitively shows. In the past, she would have been treated with standard chemotherapy. But in the last 7 to 9 years, we’ve recognized the importance, the critical benefits, of front-line EGFR TKIs compared to standard cytotoxic therapy in individuals like Ingrid.

There are now eight separate clinical trials looking at gefitinib, two at erlotinib, and two at afatinib, which she is on, that have shown clear, consistent results, a major improvement in response rate, a statistically significant and clinically meaningful improvement in PFS, and intriguingly, in the case of exon 19, [a] survival benefit, specifically for afatinib compared to standard chemotherapy. But LUX-Lung 3, which compared afatinib to pemetrexed and platinum, and then LUX-Lung 6, which compared afatinib to a gemcitabine/platinum combination in China, showed virtually identical results, the same improvement in response rate and PFS. And in those with driver mutations, exon 19, about a 10-month to 12-month absolute improvement in median survival compared to chemotherapy.

So, if Ingrid were to present to my clinic with a similar set of complaints, similar scans, similar results in her biopsy, I would have chosen exactly the same therapy, afatinib. Now, we have not compared afatinib head to head to either erlotinib or gefitinib in the front-line mutation-positive setting. Those studies have actually been completed. We’re awaiting the results but we have not yet seen the data, so it may be that they’re all equivalent, but we don’t know that for a fact. At least in post hoc retrospective analyses of the trials looking at TKIs versus chemotherapy, it’s only afatinib that has ever demonstrated a survival benefit.

There was a time when a patient who was looking forward to a vacation in Tuscany a year hence would have [had] an unrealistic expectation, certainly in 1985 or 1990. I would have encouraged that individual to move up the vacation. Now it’s actually quite realistic. She can look forward to vacations next year and potentially, two, three, four years out. There’s no guarantee. There’s certainly an attrition rate. These patients unfortunately can develop resistance and eventually refractory disease, and there is a dropoff in survival. But, on average, individuals with actionableEGFRmutations will live two to three times longer than the average unselected, non-small cell 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.