Successful treatment of EGFR T790M-mutant non-small cell lung cancer with almonertinib after osimertinib-induced interstitial lung disease: a case report and literature review

Abstract

Third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have revolutionized the standard treatment for EGFR T790M-positive non-small cell lung cancer (NSCLC). Osimertinib is one of the third-generation EGFR-TKIs and is currently the most advanced in clinical development. Interstitial lung disease (ILD) is a potentially fatal side effect of osimertinib use. Successful rechallenge with the second-generation TKI afatinib following osimertinib-induced ILD has been reported. However, few reports have discussed the safety and efficacy of third-generation TKI rechallenge in this patient population. In this paper, a case of lung adenocarcinoma is retrospectively analyzed, and the relevant literature is reviewed. The patient was initially diagnosed with early lung cancer, for which surgical treatment was performed. The postoperative diagnosis indicated stage IB (pT2N0M0) right lung adenocarcinoma. Genetic testing (amplification-refractory mutation system) revealed EGFR exon 19 deletion. More than 2 years after surgery, multiple metastases occurred in both lungs, so gefitinib (250 mg per day) was administered. However, 6 months after the start of gefitinib treatment, the tumor progressed. Lung tumor biopsy was performed for genetic testing (NGS) and an EGFR T790M mutation was observed. Subsequently, second-line treatment with osimertinib (80 mg per day) was given for 3 months. The evaluated response suggested a partial response (PR) with the occurrence of grade 3 ILD. Pemetrexed plus bevacizumab chemotherapy was subsequently administered, resulting in stable disease. However, following a severe drug reaction after six courses, the patient's chemotherapy was discontinued. Another third-generation TKI, almonertinib (110 mg per day), was rechallenged based on no ILD having been reported in a phase I/II study of this drug. After 4 months of almonertinib administration and 6 months without ILD recurrence, partial remission was attained. This is the first report of successful treatment with almonertinib after osimertinib-induced ILD. The results suggested that almonertinib had a significant effect in patients with EGFR T790M mutation, with fewer side effects and better survival benefits for patients with advanced lung cancer.

Keywords: Almonertinib; case report; epidermal growth factor receptor T790M mutation (EGFR T790M mutation); non-small cell lung cancer (NSCLC); osimertinib.