Prolonged response to atezolizumab with bevacizumab plus chemotherapy in a patient with lung cancer harboring mutation in EGFR after Afatinib treatment: A case report

Abstract Immune monotherapy is ineffective for oncogene-addicted lung cancer. This study reported the case of a patient with lung cancer harboring an epidermal growth factor receptor (EGFR) mutation that recurred after treatment with afatinib, a tyrosine kinase inhibitor (TKI). After treatment with afatinib for one year, multiple brain metastases were observed. Despite whole-brain irradiation, the lesions were resistant and progressed. Therefore, atezolizumab in combination with bevacizumab, carboplatin, and paclitaxel was administered as second-line chemoimmunotherapy. After two rounds of consolidation therapy, all intracranial metastatic lesions regressed. Maintenance therapy was administered for over 24 months. To date, all the lesions, including those in the brain and lungs, remained unchanged. To investigate why a durable response was obtained, both primary tumor-derived DNA and cell-free DNA (cfDNA) samples were extracted pre- and post-TKI therapy. Four DNA samples were analyzed by next-generation sequencing using a lung cancer-related panel. Two additional aberrations were identified in the genetic profiling cfDNA sample post-afatinib: neurofibromatosis 1 (NF1) and MUC16. The total number of somatic mutations detected pre- and post-afatinib treatment was 192 and 193 in cfDNA, and 74 and 218 in pulmonary tumor DNA, respectively. This is the foremost presentation of successful chemoimmunotherapy in a patient with lung cancer harboring an EGFR mutation with promising genetic analysis results. Moreover, the study speculated that the NF1 mutation acquired after TKI treatment, afatinib exposure before immunotherapy, and combination with an anti-angiogenesis agent were effective against EGFR-mutant cases.