Sun Kai, Wang Peng
Department Oncology, Yidu Central Hospital of Weifang, Weifang, China.
Front Oncol. 2024 Dec 17;14:1467722. doi: 10.3389/fonc.2024.1467722. eCollection 2024.
Lung cancer, including small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), is the most prevalent cancer globally and remains the leading cause of cancer-related mortality. Epidermal growth factor receptor (EGFR) mutations, frequently observed in female NSCLC patients, have revolutionized treatment strategies with the advent of tyrosine kinase inhibitors (TKIs). These therapies significantly improve survival and are considered the standard of care for patients harboring EGFR mutations. However, most patients eventually develop resistance to EGFR-TKIs, leading to disease progression. Resistance mechanisms are classified as either EGFR-dependent or EGFR-independent, the latter involving bypass pathway activation, including dysregulation of downstream signaling cascades. EGFR-independent resistance often renders all EGFR-TKIs ineffective, necessitating further investigation into resistance mechanisms.
We report the case of a 63-year-old Chinese woman diagnosed with synchronous lung adenocarcinoma harboring an EGFR exon 21 far-loop insertion mutation and clear cell renal cell carcinoma (ccRCC). A multidisciplinary team recommended systemic therapy for the lung adenocarcinoma and clinical observation for ccRCC. First-line treatment with bevacizumab plus pemetrexed-carboplatin achieved a progression-free survival (PFS) of 7 months. Second-line treatment with sintilimab and nedaplatin resulted in a PFS of 4.9 months. Third-line therapy with sintilimab and anlotinib proved ineffective. In the fourth line, the patient received furmonertinib, a third-generation EGFR-TKI, based on the FAVOUR trial. This treatment achieved durable disease control with excellent tolerability, yielding a PFS of 27 months and ongoing clinical benefit.
This case demonstrates that furmonertinib can provide significant clinical benefit to NSCLC patients with complex resistance mechanisms, including those involving the PIK3CA/mTOR pathway. These findings support its potential to overcome EGFR-TKI resistance and warrant further investigation in similar clinical contexts.
肺癌，包括小细胞肺癌（SCLC）和非小细胞肺癌（NSCLC），是全球最常见的癌症，并且仍然是癌症相关死亡的主要原因。表皮生长因子受体（EGFR）突变在女性NSCLC患者中经常被观察到，随着酪氨酸激酶抑制剂（TKIs）的出现，彻底改变了治疗策略。这些疗法显著提高了生存率，被认为是携带EGFR突变患者的标准治疗方法。然而，大多数患者最终会对EGFR-TKIs产生耐药性，导致疾病进展。耐药机制分为EGFR依赖性或EGFR非依赖性，后者涉及旁路途径激活，包括下游信号级联的失调。EGFR非依赖性耐药通常会使所有EGFR-TKIs无效，因此需要进一步研究耐药机制。
我们报告了一名63岁中国女性的病例，该患者被诊断为同时患有携带EGFR外显子21远环插入突变的肺腺癌和透明细胞肾细胞癌（ccRCC）。一个多学科团队建议对肺腺癌进行全身治疗，对ccRCC进行临床观察。贝伐单抗联合培美曲塞-卡铂的一线治疗实现了7个月的无进展生存期（PFS）。信迪利单抗和奈达铂的二线治疗导致PFS为4.9个月。信迪利单抗和安罗替尼的三线治疗被证明无效。在四线治疗中，基于FAVOUR试验，患者接受了第三代EGFR-TKI伏美替尼治疗。该治疗实现了持久的疾病控制，耐受性良好，PFS为27个月，且临床获益仍在持续。
该病例表明，伏美替尼可为具有复杂耐药机制的NSCLC患者提供显著的临床益处，包括那些涉及PIK3CA/mTOR途径的患者。这些发现支持了其克服EGFR-TKI耐药性的潜力，并值得在类似临床情况下进行进一步研究。
