EGFR G724S

Conclusions : To our knowledge, this is the largest liquid biopsy analysis comparing common/uncommon ex19dels in NSCLC and shows similar genomic findings across groups. Further work should be done to explore additional genomic and non-genomic factors to aid in patient selection for EGFR TKIs for uncommon findings.

EGFR-TKIs showed great efficacy in terms of responses and survival in patients harboring exon 18 EGFR rare mutations. This may justify the use of targeted therapies as a potential treatment strategy for these patients.

P1, N=170, Recruiting, ArriVent BioPharma, Inc.

P1, N=170, Recruiting, ArriVent BioPharma, Inc. | Phase classification: P1b --> P1

She was treated with intrathoracic infusion chemotherapy (pemetrexed 200mg+nedaplatin 20mg) on October 11, 2018...Based on the above findings, the patient was administered with gefitinib 250 mg daily as first-line therapy on November 15, 2018, and achieved partial response (PR)...On January 25, 2022, the patient was hospitalized for shortness of breath, and received intrathoracic Infusion chemotherapy (cisplatin 80mg)... The combination therapy of afatinib and osimertinib could be a new therapeutic option for patients with lung adenocarcinoma harboring EGFRG724S/T790M/19Del mutation.

Recently, we read a paper "Dacomitinib overcomes afatinib-refractory carcinomatous meningitis in a lung cancer patient harbouring EGFR Ex.19 deletion and G724S mutation" published in Investigational New Drugs. To share our experience, we present a case of 58-year-old man with a long-term response to afatinib in a patient with previously unreported compound EGFR mutation. In patients with rare compound EGFR mutations, afatinib might be one of the treatment option.

A patient diagnosed with advanced EGFR-mutated (exon 19 deletion) NSCLC after several lines of treatment - gefitinib, osimertinib, heat shock protein inhibitors and chemotherapy-developed EGFR G724S mutation retaining the exon 19 deletion. She was then treated successfully with afatinib leading to a progression free survival of 9 months (and counting). This is the first report of the emergence of G724S mutation, together with ex19del, after three subsequent lines of therapy following progressive disease to Osimertinib, and we report for the first time the activity of afatinib against EGFR exon 18 G724S mutation in this setting.

Dacomitinib may be effective choice in afatinib-refractory carcinomatous meningitis harboring G724S mutation. This is the first case report showing that a change to dacomitinib responded to afatinib refractory cancerous meningitis.

Acquired resistance in EGFR mutant NSCLC remains very heterogeneous; the frequency of individual mutations is low, one of the reasons might be lack of testing at resistance. While T790M and C797S mutations are well described, this report also documents a significant number of L718V mutations, primarily in osimertinib-treated pts with an original L858R. These data support the need to increase NGS evaluation of patients with EGFR mutant lung cancers who have developed clinical resistance.