Epidermal growth factor receptor mutation heterogeneity analysis of pulmonary sarcomatoid carcinoma successfully treated with erlotinib: A case report

Abstract

Abstract. Pulmonary sarcomatoid carcinoma (PSC) is a rare histological subtype of non-small cell lung cancer, and the available studies on the response to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is limited. In the present study, a 73-year-old female presented with a large mass in the lower right lung, which was diagnosed as a PSC on biopsy. An amplification-refractory mutation system (ARMS) test revealed that the patient possessed the wild-type EGFR gene, and the patient subsequently underwent radiotherapy (60 Gy) and four 21-day cycles of chemoradiotherapy (1,600 mg gemcitabine, days 1 and 8; 30 mg, cisplatin, days 1-3). Following radiotherapy and chemotherapy treatment, a CT scan revealed complete remission of the mass in the lower right lung, however, metastases were identified in the paraaortic lymph node, bilateral iliac fossa and the right gluteal region. Notably, an EGFR exon 21 L858R gene mutation was identified in the mass of the right gluteal metastasis. Therefore, treatment with erlotinib was initiated. The patient continued to experience progression-free survival for six months following the initiation of erlotinib therapy. However, multiple metastases were then identified, and all lesions possessed the wild-type EGFR gene, as identified by the ARMS test. The findings suggest that erlotinib is a viable therapeutic option for the treatment of PSC patients that possess an EGFR mutation. The spatio-temporal evolution of EGFR mutational heterogeneity in PSC may result in drug-resistance, which challenges EGFR-TKI therapy and EGFR gene mutation diagnosis.

Pulmonary Sarcomatoid Carcinomas Commonly Harbor Either Potentially Targetable Genomic Alterations or High Tumor Mutational Burden as Observed by Comprehensive Genomic Profiling

“…[10][11][12][13][14] However, recent studies have identified targetable hepatocyte growth factor receptor gene (MET) exon 14 skipping and KRAS alterations in a significant fraction of cases. 12,15,16 Isolated reports of responses to targeted therapy have been presented, 15,17,18 but PSC remains a tumor type with little demonstrated efficacy of any targeted therapy in the clinic. Herein, we present results of comprehensive genomic profiling (CGP) of the largest series to date of patients with PSC, including patients with diverse genomic alterations (GAs) experiencing clinical benefit to targeted therapies and immunotherapy.…”

KRAS mutation is predictive of outcome in patients with pulmonary sarcomatoid carcinoma

“…KRAS mutation has been reported in up to 38% of PSCs and EGFR mutations in up to 25% . Furthermore, few recent studies have identified targetable MET exon 14 skipping in a significant fraction of cases, with a few case reports demonstrating a great response to targeted therapy with MET inhibitors . Despite these advancements, there are still limited options available for treatment of these tumours.…”

“…6,[8][9][10] Furthermore, few recent studies have identified targetable MET exon 14 skipping in a significant fraction of cases, 3,7,9 with a few case reports demonstrating a great response to targeted therapy with MET inhibitors. 11,12 Despite these advancements, there are still limited options available for treatment of these tumours. In addition, there are no clinicopathological or molecular features that could predict outcome reliably in PSC patients.…”

DNA Repair Genes ERCC1 and BRCA1 Expression in Non-Small Cell Lung Cancer Chemotherapy Drug Resistance

“…First-line chemotherapy drugs for NSCLC include platinum, such as cisplatin and carboplatin, while platinum resistance often leads to chemotherapy failure [ 13 , 14 ]. Platinum drugs can combine with nucleophilic DNA in tumor cells to form DNA-platinum adduct, thus inhibiting DNA replication, causing DNA damage, and ultimately inducing tumor cell death [ 15 ]. However, the DNA damage repair system can modify DNA damage to various extents, which affects the sensitivity of chemotherapy drugs.…”