Multimodality Treatment of Pulmonary Sarcomatoid Carcinoma: A Review of Current State of Art

Abstract

Pulmonary sarcomatoid carcinoma (PSC) is an unconventional non-small-cell lung cancer (NSCLC) that is currently managed under guidelines used for conventional NSCLC and has poor survival. Surgery is the optimal choice for resectable PSC, and the prevalence of mutations in this type of tumor laid the foundation for novel systemic therapies such as targeted therapy and immunotherapy. PSC is resistant to chemotherapy and radiotherapy, and the effects of the 2 therapies are controversial. Targeted therapies have been reported to confer survival benefits, and savolitinib, an oral selective MET tyrosine-kinase inhibitor, has been approved in metastatic patients with MET exon 14 skipping mutations. Expression and positive rate of programmed death ligand 1 in PSC are high; our previous research has also revealed a high mutational burden and a T-cell-inflamed microenvironment of PSC. Correspondingly, immune checkpoint inhibitors have shown preliminary antitumor effects (overall response rates of 40.5% (15/37) and 31.6% (6/19) in two retrospective studies, respectively) in PSC patients. In summary, patients should receive operations at an early stage and multimodality treatments are needed to maximize the benefits of patients with advanced disease.

Capmatinib in patients with MET-positive advanced non-small cell lung cancer: analysis of the Russian cohort in the Geometry mono-1 study

“…Стандартные варианты лечения, такие как химиотерапия или ингибиторы контрольных точек иммунного ответа, имеют достаточно низкую эффективность у пациентов с драйверными мутациями в 14 экзоне гена MET [15,16]. Это представляет неудовлетворенную потребность и серьёзную клиническую проблему.…”

Demographics and Clinicopathologic Profile of Pulmonary Sarcomatoid Carcinoma with Survival Analysis and Genomic Landscape

“…With more expansive genomic profiling, there will be increased opportunity for novel targeted therapies. For example, in June 2021, savolitinib, an oral MET tyrosine-kinase inhibitor, was approved for treatment in PSC patients that exhibit the MET exon 14 skipping mutation in China [26,45]. Analysis of the PSC immune microenvironment has also revealed TMB, LF, and the expression of programmed cell death ligand 1 (PD-L1), indicating promising potential for immune checkpoint inhibitors.…”

“…In fact, anti-PD-1/PD-L1-based therapies are now recommended as first-line treatments for late-stage/metastatic NSCLC regardless of PD-L1 expression. Immunotherapies such as durvalumab, tremelimumab, and nivolumab show promising effects on PSC [45][46][47]. So, while surgical resection is the preferred treatment modality in earlier stages, the effects of chemotherapy and radiotherapy in PSC treatment are being studied.…”

MET alterations in advanced pulmonary sarcomatoid carcinoma

“…Compared with the common type of non-small cell lung cancer, the incidence of METex14 skipping mutation is significantly higher in PSC (7). It is important to improve the sensitivity and specificity of the genetic testing for METex14 skipping mutation, which is an independent driver mutation of NSCLC without exception for PSC and its clinical significance is more prominent.…”

“…Pulmonary sarcomatoid carcinoma (PSC) is a rare subset of NSCLC that accounts for about 0.5-1% of all primary lung carcinoma, and its malignant biological behavior is more aggressive than other pathological types of lung cancer (5)(6)(7). According to the World Health Organization (WHO) Classification of Lung Tumors (2015 version), PSC is defined as a group of poorly differentiated NSCLC containing a component of sarcoma-like elements or true sarcomatous areas that is currently solely based on morphological characteristics, and is divided into five subtypes such as spindle cell carcinoma (a carcinoma almost completely composed of epithelial spindle cells), giant cell carcinoma (a carcinoma almost entirely composed of tumor giant cells), pleomorphic carcinoma (a poorly differentiated NSCLC that contains at least 10% spindle and/or giant cells or a carcinoma consisting only of spindle and giant cells), carcinosarcoma (a mix of NSCLC and true sarcoma) and biphasic pulmonary blastoma (a tumor composed of embryonal-type epithelial elements and primitive mesenchymal stroma) (6,8).…”