Thu-Lan T. Luonga; Chelsea N. Powers, PhDa; Brian J. Reinhardt, MSa; Michael J. McAnulty, PhDa; Peter J. Weina, MDb; Karen J. Shou, DOa; Caban B. Ambar, MSa
Correspondence: Thu-Lan T. Luong (thu-lan.t.luong.civ@health.mil)
aWalter Reed National Military Medical Center, Bethesda, Maryland
bFort Belvoir Community Hospital, Virginia
Author disclosures
The authors report no actual or potential conflicts of interest or outside sources of funding with regard to this article.
Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the Department of Defense, the US Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
Ethics and consent
The study protocol was approved by the Walter Reed National Military Medical Center Institutional Review Board and complied with the Health Insurance Portability and Accountability Act as an exempt protocol.
The difference between erlotinib and gefitinib data can be attributed to the FDA approval date and gefitinib’s association with a higher frequency of hepatotoxicity.18-20 The FDA designated gefitinib as an orphan drug for EGFR mutation–positive NSCLC treatment. Gefitinib first received accelerated approval in 2003 for the treatment of locally advanced or metastatic NSCLC. Gefitinib then was voluntarily withdrawn from the market following confirmatory clinical trials that did not verify clinical benefit.
The current approval is for a different patient population—previously untreated, metastatic EGFR exon 19 or 21 L858R mutation—than the 2003 approval.4,6 There was no record of gefitinib use after 2017 in our study.
Erlotinib is a reversible EGFR-TKI that is approved by the FDA as first-line (maintenance) or second-line treatment (after progression following at least 1 earlier chemotherapy regimen) for patients with metastatic NSCLC who harbor EGFR exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test.3 Since 2005, the FDA also approved erlotinib for first-line treatment of patients with locally advanced, unresectable, or metastatic pancreatic cancer in combination with gemcitabine.3 Without FDA indication, erlotinib is used for colorectal, head and neck, ovarian carcinoma, pancreatic carcinoma, and breast cancer.21
Erlotinib and gefitinib are not considered first-line treatments in EGFR exon 19 or 21–mutated NSCLC because osimertinib was approved in 2018. Targeted therapies for EGFR mutation continue to advance at a fast pace, with amivantamab and mobocertinib now FDA approved for EGFR exon 20 insertion–mutated NSCLC.
Erlotinib Use
Thirty-nine patients (10%) in this study were prescribed erlotinib for off-label indications. Erlotinib was used alone or in combination with bevacizumab, capecitabine, cisplatin, denosumab, docetaxel, gemcitabine, and the MEK-inhibitor selumetinib. Erlotinib combined with cisplatin, denosumab, docetaxel, and gemcitabine had no recorded AEs, with 10 data entries for gemcitabine and 1 for other drugs. Three patients received bevacizumab and erlotinib, and 1 patient (diagnosed with kidney NOS) showed rash or facial swelling/erythema and diffuse body itching then stable disease after 2 cycles.
One patient (diagnosed with cancer located at the pancreas head) was bridged with capecitabine and erlotinib when going on a vacation, then received FOLFIRINOX (a combination chemotherapy regimen containing folinic acid [leucovorin], fluorouracil, irinotecan, and oxaliplatin), which led to significant fatigue, blurry vision, and constipation. One patient was treated for lung NOS with the MEK-inhibitor selumetinib plus erlotinib and developed pneumonitis following treatment.
Because oncologists followed guidelines and protocols in systemic treatment, DDIs of erlotinib concurrently (before or after) and in combination with cancer drugs were unlikely. Further investigation is needed for several 1:1:1 DDIs with noncancer drugs. A retrospective overview is not a randomized clinical study; therefore, analysis is limited. Data from the MHS were obtained solely from notes from physicians who treated the patients; therefore, exact information explaining whether a patient completed treatment or had to withdraw could not be extrapolated (ie, blood/plasma samples were not obtained to confirm).
Discontinued Treatment
The reasons for treatment discontinuation with erlotinib or gefitinib varied among patients, with no consistent AE or cause. Most data were for switching treatments after discontinuing treatment with erlotinib (101 of 123 patients) and gefitinib (2 of 5 patients). This is not surprising given the widely recognized pillars of therapy for NSCLC: chemotherapy, target therapy, and immunotherapy.22 From the MHS records, the reasons patients switched treatment of erlotinib or gefitinib were not listed or listed as due to negative EGFR testing, lack of responsiveness, or enrollment in a different treatment.
