Corey J. Langer, MD: Use of TKI Therapy in Patients with EGRF Exon 21 Substitutions (L858R)
What efficacy data support the use of this TKI therapy in a patient such as Sarah with EGFR exon 21 substitutions (L858R)?
Afatinib has garnered FDA approval forEGFRmutations regardless of the nature of mutation, as long as they’re actionable. So either exon 19 or exon 21 are clearly actionable, and the two critical phase III trials that prospectively assessed afatinib in this setting demonstrated a statistically significant and clinically meaningful improvement in both response rate and PFS versus standard chemotherapypemetrexed and platinum in LUX-Lung 3 and gemcitabine and platinum in LUX-Lung 6. In fact, those two trials were the largest prospective phase III trials ever conducted in individuals withEGFRmutations.
So afatinib’s role is clearly established. It’s on par at least with erlotinib and now gefitinib, which was recently re-approved specifically in this setting. Unlike exon 19, however, afatinib has not demonstrated an actual survival benefit versus chemotherapy in this setting. So, at least in terms of efficacy, we can’t necessarily point to afatinib as necessarily superior to erlotinib or gefitinib or infer that it might be superior. But it’s at least on par. With respect to toxicity, it can be a challenge. For Sarah, who has a very busy life, certainly cancer was not on her agenda. It never is, but she wants to maximize both her benefit and her quality of life and minimize toxicity.
CASE 2: mNSCLC
Sarah W. is a 58-year old physical therapist from Brooklyn, New York who is also active in a community theater group; her prior medical history is notable for mild GERD controlled with diet and proton pump inhibitor, and hyperlipidemia, controlled with atorvastatin.
She has a 12-pack-year smoking history but quit about 20 years ago after developing a severe respiratory infection. After showing chest x-ray abnormalities on a routine visit to her PCP, she is referred for further evaluation.
Her initial CT scan shows multiple bilateral lung nodules, a large 8-cm mass in the left upper lobe (LUL), suspicious for malignant pleural effusion, and several hepatic nodules
Transbronchial biopsy of the LUL mass shows adenocarcinoma T3 (based on size); biopsy of the hepatic nodules was consistent with metastatic disease, and she was deemed unresectable on surgical consult
Mutational status was reported asEGFRexon 21 (L858R) substitution; no other actionable mutations detected
At the time of diagnosis the patients performance status is 0
Sarah wishes to continue with her normal work schedule and rehearsals for an upcoming community theater production. Her oncologist initiates her on afatinib 40 mg/day.
At her 2-week follow-up, she shows symptoms of increasing diarrhea (≥6 stools/day), which has not improved with antidiarrheals, and a papular rash on her upper arms
Rash is not very itchy or bothersome, however, diarrhea interferes with both her work schedule and rehearsals
Diet modifications and loperamide are recommended for diarrhea, and topical corticosteroids for her rash; she continues therapy at 40 mg/day
At 3 months, while other symptoms have begun to improve, she shows symptoms of gingival stomatitis, and the nursing team recommends diet modifications and a mouth rinse as needed; she continues therapy at 40 mg/day
At her next follow-up, CT scan shows stable disease, with shrinkage in the primary mass and no new hepatic nodules.
Her diarrhea has improved to grade 1 with loperamide and diet; stomatitis and rash have been effectively managed with prior recommendations
