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

Abstract

The most serious adverse reaction associated with treatment with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is drug-induced interstitial lung disease (ILD). Because EGFR-TKIs are key drugs for patients with non-small cell lung cancer who have somatic activating mutations of the epidermal growth factor receptor gene (EGFR mutations), several cases of retreatment with EGFR-TKIs after ILD induced by these drugs have been reported. Here, we present a 68-year-old man with lung adenocarcinoma and leptomeningeal metastases having an EGFR mutation who was retreated with erlotinib after erlotinib-induced ILD. He suffered no ILD recurrence and his leptomeningeal metastases dramatically improved. In addition to the present case, reports of nine patients who were retreated with EGFR-TKIs after ILD were found in the literature. Only one patient had recurrence of ILD (although seven were retreated at a reduced dose of EGFR-TKIs, including the patient with recurrence). In contrast, three patients had no recurrence of ILD even without dose-reduction. These reports suggest that dose-reduction plays a limited role in preventing recurrence. Many patients received corticosteroids during retreatment, but not the one with recurrence of ILD. This may suggest that corticosteroids can prevent recurrence due to their antiinflammatory properties.

Successful Crizotinib Retreatment after Crizotinib-Induced Interstitial Lung Disease

“…4 Recent reports describe the safety and efficacy of EGFR-TKI retreatment, even after EGFR-TKI-induced ILD, and imply the need for steroid pretreatment to reduce ILD recurrence. 5 In case of crizotinib, there have not been any previous reports on the retreatment after crizotinib-induced ILD. Thus, dexamethasone was used in our case after the example of EGFR-TKI retreatment.…”

EGFR Exon 19 Deletion Mutations and Systemic/Central Nervous System Miliary Metastasis: Clinical Correlations and Response to Therapy

“…5, 6 Furthermore, EGFR deletion 19 mutations may be predictive for improved outcomes for leptomeningeal metastasis as suggested by a recent cohort study that demonstrated that patients with EGFR deletion 19 mutations have improved clinical outcomes when compared to EGFR exon 21 mutation and EGFR wild-type cohorts with leptomeningeal metastasis. Median time to progression or symptom deterioration for patients with leptomeningeal metastasis was 7.8 months in the exon 19 deletion subgroup compared to 0.9 and 1.9 months in the wild type and exon 21 mutation cohorts, respectively.…”

Successful erlotinib rechallenge after both gefitinib‐ and erlotinib‐induced interstitial lung diseases

“…While the average mortality rate of all 70 cases was 44.3%, that of 20 DAD pattern cases was 75%. DAD pattern was never seen in radiological images reported in successful EGFR-TKI rechallenge [ 4 ]. Both ILDs in the present case also have diffuse ground glass opacity suggesting non-DAD pattern.…”