Long-Term Survival of Over 6 Years with Afatinib Sequential Treatment in a Patient with EGFR Mutation-Positive Non-Small Cell Lung Cancer: A Case Report

Abstract

Lung cancer is the leading cause of cancer-related death worldwide [1], with non-small cell lung cancer (NSCLC) accounting for approximately 85% of all cases [2], and lung adenocarcinoma and squamous cell carcinoma representing the most common NSCLC subtypes [3]. An increased understanding of the genomic landscape in NSCLC has led to the identification of targetable molecular pathways and the subsequent development of highly targeted treatments that demonstrate substantial clinical benefit compared with traditional platinum-based chemotherapy [4]. In particular, identification of epidermal growth factor receptor (EGFR) activation—most commonly resulting from L858R point mutation or deletions within exon 19 (Del19)—as an oncogenic driver in NSCLC, has led to the development and approval of several EGFR tyrosine kinase inhibitors (TKIs) [5]. Among these, afatinib, an ErbB family blocker that irreversibly binds and inhibits the activity of EGFR, HER2 (ErbB2), and HER4 (ErbB4), and blocks transphosphorylation of HER3 (ErbB3) [6], is approved for first-line treatment of NSCLC in patients with non-resistant (sensitizing) EGFR mutations [7, 8]. Unfortunately, acquired resistance is a key challenge in the use of EGFR TKIs, and almost all patients ultimately experience tumor progression despite high initial response rates [9, 10]. The predominant resistance mechanism, detected in 50–70% of tumors [11–13], is the secondary EGFR T790M mutation, which appears to result in steric interference of EGFR TKI binding [14], or enhanced EGFR affinity for ATP [15, 16]. Several third-generation EGFR TKIs have been developed to overcome T790M-driven resistance, including osimertinib, an irreversible inhibitor of EGFR-sensitizing and T790M-resistance mutations, with selectivity over wild-type EGFR [17]. However, resistance to osimertinib is also inevitable, occurring through heterogeneous mechanisms, including acquisition of tertiary EGFR mutations or EGFR-independent mechanisms [9]. Given the availability of several EGFR-targeted drugs, there is currently considerable debate regarding optimal treatment sequencing in EGFR mutation-positive NSCLC to maximize long-term clinical benefit, with little direct evidence from comparative trials available to inform these decisions [5, 18, 19]. Herein, we describe the case of a patient with pleural-disseminated EGFR mutation-positive stage IV lung adenocarcinoma, who achieved long-term clinical benefit of more than 6 years with sequential EGFR TKI treatment. A 38-year-old non-smoking Chinese male, with no family history of tumors, presented with an intermittent cough in June 2009. Computed tomography (CT) scans showed a flaky shadow on the left lower lung; subsequent follow-up 5 months later indicated no change in the lesion and carcinoembryonic antigen (CEA) level was normal (≤ 5 ng/ mL). In November 2010, however, CT scan indicated that the lesion had become denser, and blood CEA level was 110 ng/mL. Subsequent positron emission tomography/ CT scan indicated stage IB lung cancer (cT2aN0M0 [7th edition of tumor, node, metastasis [TNM] classification]). The patient was followed-up until December 2010, when video-assisted thoracic surgery (VATS) was performed. During VATS, bloody pleural effusion (80 mL) was identified, and multiple widespread nodules were observed in the parietal pleura, pericardium, and diaphragmatic muscle. The parietal nodules, found accidentally and which had not been observed in the CT scan before surgery, were removed * Yi-Long Wu [email protected]