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 thirdgeneration 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.

Aumolertinib challenge as an optional treatment in advanced non small‑cell lung cancer after osimertinib failure with epidermal growth factor receptor‑sensitive mutation: A case series

“…In a case report by Shen et al ( 20 ), almonertinib overcame osimertinib resistance associated with the L718Q mutation in a patient with metastatic NSCLC. Wu et al ( 21 ) and Zhang et al ( 22 ) reported successful treatment with aumolertinib after osimertinib-induced interstitial lung disease and cardiotoxicity. These results suggested a potential agent for reversing drug osimertinib-resistance and indicated a better safety profile for aumolertinib compared with that for osimertinib.…”

“…One is that aumolertinib carries lower half maximal inhibitory values for T790M and L858R mutations, and T790M and Del 19 mutations, respectively, than osimertinib (i.e., 0.29 vs. 0.46 nmol/l, and 0.21 vs. 0.29 nmol/l) ( 23 ). The other is that aumolertinib may partly overcome the drug resistance of osimertinib in advanced NSCLC ( 21 ). Finally, the mean plasma concentration of aumolertinib (110 mg/day) is slightly higher than that of osimertinib (80 mg/day) (155.5 vs. 138.98 ng/ml) ( 24 ).…”

Effects of voriconazole and fluconazole on the pharmacokinetics of almonertinib in rats by UPLC–MS/MS

“…Almonertinib has high selectivity to EGFR‐sensitizing mutation and T790M‐resistance mutation and also has good central nervous system activity (Yang et al, 2020). Moreover, it effectively blocks the production of non‐selective active metabolite AZ5104 and has significantly improved safety compared with osimertinib (Nagasaka et al, 2021; Wu, Zhong, et al, 2021). Almonertinib is a moderately sensitive substrate of CYP3A4 in vivo and mainly metabolized to HAS‐719 in the liver.…”

Safety of Tepotinib Challenge after Capmatinib-Induced Pneumonitis in a Patient with Non-Small Cell Lung Cancer Harboring MET Exon 14 Skipping Mutation: A Case Report

“…Once pneumonitis occurs, the permanent discontinuation of MET inhibitors and corticosteroid treatment have been suggested [ 6 ]. Other types of target agents within the same class have been used after drug-induced pneumonitis in patients receiving EGFR-TKI [ 9 , 10 , 11 ] and ALK inhibitors [ 12 ]. However, the safety of using another MET inhibitor after discontinuing the first remains largely unknown and such patients have rarely been reported.…”