Metastatic NSCLC with Corey J. Langer, MD, David Spigel, MD, Denise O'Dea, NP, and Jack West, MD: Case 1 - Episode 1
What efficacy data support the use of this TKI therapy in a patient such as Ingrid with EGRF exon 19 deletion NSCLC?
We now have multiple, prospective, randomized, phase III studies that show if you take patients who have so-called activatingEGFRmutations, whether exon 19 deletions or L858R mutations, and you randomize them to an EGFR TKI, that could be erlotinib or gefitinib, or, in this case, afatinib, those patients will always do better versus chemotherapy in terms of PFS. What’s interesting about this case is that the patient received afatinib for an exon 19 deletion. That scenario has recently become a topic of discussion and debate because there were two large randomized trials that afatinib was compared against chemotherapy.
One was called the LUX-Lung 3 trial, which compared afatinib versus cisplatin and pemetrexed in a global population, although about a third was Asian, and then a second trial, which was called the LUX-Lung 7, which compared afatinib versus cisplatin and gemcitabine. In those two trials, if you look at the patients who had exon 19 deletions, not only was there a PFS advantage for afatinib, but there was an overall survival advantage. So one of the messages these days, and this is what’s debated, is that if you have a patient with an exon 19 deletion, afatinib might be a drug you should think about first.
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.