Abstract YO30
Case summary
Background: Third-generation EGFR-TKIs have emerged as the preferred first-line treatment option for advanced NSCLC patients harboring EGFR mutations (19Del/Ex21L858R). However, EGFR-TKIs resistance is inevitable and the underlying mechanisms of resistance vary. ICIs (Immune Checkpoint Inhibitors) treatmemt following EGFR-TKI resistance often yields unsatisfactory results. Therefore, delaying the onset of initial EGFR-TKI resistance is crucial. One potential approach is escalating the dose of EGFR-TKI to delay initial resistance and prolong survival benefits.
Method: A 53-year-old male patient was diagnosed with adenocarcinoma of the right upper lung, classified as Stage IVB (T2aN2M1c), featuring lymph node metastasis, pulmonary metastasis and bone metastasis. The genetic testing revealed a co-mutation of 19del and TP53.
Results: On April 26, 2020, the patient received aumolertinib 110mg QD as first-line treatment. After three months, chest CT scan showed a reduction in the lesion size, achieving partial response (PR). The duration of tumor remission exceeded 26 months. Until June 23, 2022, he experienced disease progression. NGS re-testing revealed that the sensitive gene mutation of 19del combined with TP53 co-mutation still existed. The dosage of aumolertinib increased to 165mg as rechallenge, and the tumor remained stable for up to 11 months without any obvious symptoms. On May 9, 2023, the patient experienced disease progression again. On the basis of aumolertinib 165mg, carboplatin (400mg) + pemetrexed (0.8g) were added for four cycles. At data cut-off, he is still undergoing continuous PR and follow-up with an acceptable safety profile.
Conclusion: After resistance to third-generation EGFR-TKIs, it is crucial to promptly identify the resistance mechanism. For patients who still harbor sensitive gene mutations, increasing the dosage of treatment or combining with chemotherapy are the promising options for subsequent treatment.