Successful rechallenge with erlotinib in a patient with EGFR-mutant lung adenocarcinoma who developed gefitinib-related interstitial lung disease

Abstract

Small-molecule tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR) pathways are used clinically for patients with non-small cell lung cancer (NSCLC). It is well established that somatic mutations in the kinase domain of the EGFR (Lynch et al. in N Engl J Med 350:2129-2139, 2004; Paez et al. in Science 304:1497-1500, 2004) are strongly associated with the tumor response and clinical outcomes in patients with NSCLC receiving EGFR-TKIs (Mitsudomi and Yatabe in Cancer Sci 98:1817-1824, 2007). Although the most common adverse events are skin rash and diarrhea, the most serious adverse effect reported is drug-related interstitial lung disease (ILD) (Inoue et al. in Lancet 361:137-139, 2003; Ando et al. in J Clin Oncol 24:2549-2556, 2006). The precise mechanism underlying the development of drug-related ILD remains unknown. Here, we describe a case of EGFR-mutant NSCLC who was rechallenged with the small-molecule EGFR antagonist erlotinib after developing gefitinib-related ILD.

Differences in adverse events between 250mg daily gefitinib and 150mg daily erlotinib in Japanese patients with non-small cell lung cancer

“…However, there was no significant difference in LFT abnormalities or pneumonitis between the two groups. Some cases of successful treatment with erlotinib after gefitinib-related hepatotoxicity or gefitinib-related pneumonitis have also been reported, which suggests differing mechanisms of actions for these two drugs with respect to liver and lung toxicity [19][20][21][22]. Gefitinib and erlotinib share a common base structure (4-anilinoquinazoline) but differ in the substituents attached to the quinazoline and anilino rings.…”

Successful erlotinib rechallenge for leptomeningeal metastases of lung adenocarcinoma after erlotinib-induced interstitial lung disease: A case report and review of the literature

“…Three received gefitinib after gefitinib-induced ILD [17,18,24], 5 were treated with erlotinib after gefitinib-induced ILD [19][20][21][22], and the remaining one (two including the present case) received erlotinib after erlotinibinduced ILD [23]. Two patients were Asians and the other reports were also from Asia, but the ethnicity of the patients was not stated.…”

“…In addition to the present case, a literature search identified a total of nine cases who received EGFR-TKI retreatment after ILD induced by these drugs (Table 1) [17][18][19][20][21][22][23][24]. Three received gefitinib after gefitinib-induced ILD [17,18,24], 5 were treated with erlotinib after gefitinib-induced ILD [19][20][21][22], and the remaining one (two including the present case) received erlotinib after erlotinibinduced ILD [23].…”

Erlotinib Achieved Partial Response in a Non-Small Cell Lung Cancer Patient with Gefitinib-Induced Interstitial Lung Disease

“…Although a case with recurrent gefitinib-induced ILD was reported [2], a reduced dose of gefitinib might induce a response without recurrent gefitinib-induced ILD [3]. Several cases of NSCLC successfully rechallenged with erlotinib after developing gefitinib-induced ILD were also described [4, 5]. We add another case report which shows that a reduced dose of erlotinib in combination with steroid therapy achieved partial response in a patient recovered from gefitinib-induced ILD.…”