Concurrent TP53 Mutations Facilitate Resistance Evolution in EGFR Exon 20 S768I Mutant Lung Adenocarcinoma: A Case Report and Review of the Literature

Introduction
Lung adenocarcinoma is the most common subtype of non-small cell lung cancer (NSCLC), with epidermal growth factor receptor (EGFR) mutations being the most frequently observed driver alterations. Among these, mutations in exons 18–21 are predominant, particularly exon 19 deletions and the L858R mutation in exon 21. Less common EGFR mutations include S768I, G719X, and exon 20 insertions. Additionally, co-occurring mutations, such as those in TP53, are frequently detected in lung adenocarcinoma patients with EGFR alterations.
Case Presentation
This study presents a retrospective analysis of Alflutinib neoadjuvant therapy for lung adenocarcinoma, supplemented by a review of relevant literature. The patient was diagnosed with T4N3M1a, stage IVa disease. Initial treatment consisted of chemotherapy with pemetrexed (860 mg) and carboplatin (480 mg), along with immunotherapy using sintilimab (200 mg). While the patient exhibited a favorable initial response, follow-up CT imaging revealed disease progression.
Next-generation sequencing identified an EGFR exon 20 missense mutation (p.S768I and p.V774M) alongside a TP53 (p.Y220C) missense mutation, with mutation abundances of 48.6%/49.7% and 49.2%, respectively. Consequently, the treatment regimen was modified to include chemotherapy with albumin-bound paclitaxel (400 mg) and pembrolizumab (200 mg), followed by targeted therapy with oral afatinib, yielding a progression-free survival (PFS) of 12 months. Subsequently, brain metastases developed, prompting a switch to osimertinib, which resulted in a PFS of 9 months. Despite significant therapeutic efficacy, severe side effects led the patient to discontinue treatment independently.
Five months later, disease progression was observed, accompanied by an increase in carcinoembryonic antigen (CEA) levels. The patient was then treated with furmonertinib and sunvozertinib, each providing a PFS of 3 months. Although CEA levels initially decreased, they later rebounded, signaling further disease progression and a worsening clinical condition.
Conclusion
This case highlights the superior PFS outcomes associated with afatinib and osimertinib in patients harboring EGFR S768I/V774M and TP53 mutations compared to furmonertinib and sunvozertinib. Additionally, the combination of platinum-based chemotherapy and immunotherapy may serve as a promising neoadjuvant strategy for patients with stage IVa NSCLC.