“Lazarus effect” in patient affected by lung adenocarcinoma carrying EGFR, CTNNB1, MET exon 11 and PIK3CA mutations treated with gefitinib

Abstract

: Lung cancer is the most commonly diagnosed tumor and the leading cause of cancer death. Molecular diagnosis allows the identification of different subgroups of non-small cell lung cancer (NSCLC), the so called “oncogene-addicted” cancers and determines therapeutic strategies for patients with non-small-cell lung cancer-adenocarcinoma (NSCLC-A). In fact, molecular profiling is now a well-established routine practice in patients with NSCLC. Next generation sequencing (NGS) allows to identify multiple concurrent mutations, whose clinical impact often remains unclear. EGFR tyrosine kinase inhibitors (EGFR-TKIs) have dramatically improved the outcomes of patients affected by EGFR-mutated lung adenocarcinoma. In our work, we report the case of a 60-years old female who was diagnosed with metastatic lung adenocarcinoma. NGS sequencing was performed and showed EGFR exon 19 deletion, CTNNB1 exon 3 mutation, MET exon 11 mutation and PIK3CA exon 2 mutation. We started first-line treatment with gefitinib (250 mg daily) achieving an immediate improvement in clinical condition (a so called “Lazarus effect”) and a partial response after only 7 days of treatment. The patient is still alive and on treatment with gefitinib after 7 months without signs of disease progression. Although concurrent mutations of CTNNB1, MET and PIK3CA are regarded as negative prognostic factors in patients affected by EGFR-mutated NSCLCs; our patient showed an impressive response to EGFR-TKI, suggesting that in our case EGFR acts as “driver mutation”. The presence of these specific concurrent mutations doesn’t affect the response to EGFR-TKI.