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Use of savolitinib as neoadjuvant therapy for non-small cell lung cancer patient with MET exon 14 skipping alterations: A case report.

ABSTRACT: Savolitinib is a tyrosine kinase inhibitor being developed for the treatment of metastatic non-small cell lung cancer (NSCLC) with mesenchymal-epithelial transition (MET) factor exon 14 skipping alterations. However, the role of savolitinib in neoadjuvant therapy for lung cancer remains unclear. Here, we present a case of a 65-year-old woman diagnosed with stage IIIA (cT2bN2M0, eighth TNM stage) upper right lung adenocarcinoma harboring MET exon 14 skipping alterations. After 4 weeks of therapy, a partial response was achieved with neoadjuvant savolitinib, and significant shrinkage in tumor and lymph nodes was observed. We also measured the immune microenvironment of the primary tumor pre- and posttreatment with savolitinib.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC9514319 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Use of savolitinib as neoadjuvant therapy for non-small cell lung cancer patient with MET exon 14 skipping alterations: A case report.

Zhang Yu Y Zhang Hao H Wang Hanqing H Zeng Jingtong J Zhang Bo B Zhou Ning N Zu Lingling L Song Zuoqing Z Wang Changli C Xu Song S

Frontiers in oncology 20220908

Savolitinib is a tyrosine kinase inhibitor being developed for the treatment of metastatic non-small cell lung cancer (NSCLC) with mesenchymal-epithelial transition (MET) factor exon 14 skipping alterations. However, the role of savolitinib in neoadjuvant therapy for lung cancer remains unclear. Here, we present a case of a 65-year-old woman diagnosed with stage IIIA (cT2bN2M0, eighth TNM stage) upper right lung adenocarcinoma harboring MET exon 14 skipping alterations. After 4 weeks of therapy, ...[more]

PMID: 36176406

Similar Datasets

Neoadjuvant Savolitinib targeted therapy stage IIIA-N2 primary lung adenocarcinoma harboring MET Exon 14 skipping mutation: A case report.

Project description:MET exon 14 skipping mutation (METex14m) is rare and occurs in approximately 1-4% of all non-small cell lung cancer (NSCLC) patients and approximately 2.8% of resected stage I-III NSCLC patients. Savolitinib is an oral, potent and highly selective type Ib MET inhibitor, which has been shown to be promising activity and acceptable safety profile in patients with advanced NSCLC harboring METex14m. Most recently, many studies have been probing into the feasibility and efficacy of target therapy for perioperative application in NSCLC. Interestingly, there are very few recorded cases of such treatments. Here, we presented that systemic treatment with the MET inhibitor savolitinib before surgery could provide the potential to prolong overall survival (OS) of patients with locally advanced potentially resectable NSCLC. A 49-year-old woman was diagnosed with stage IIIA (T2bN2M0) primary lung adenocarcinoma exhibiting a METex14m by real-time quantitative polymerase chain reaction (RT-qPCR). Given that the tumor load and the size of lymph nodes experienced a significant downstaging after the neoadjuvant treatment of savolitinib with 600mg once a day for 5 weeks, left lower lobectomy and systemic lymphadenectomy were successfully performed. The pathological response was 50% and the final postoperative pathological staging was pT1cN0M0, IA3 (AJCC, 8th edition). The case provides empirical basis for the neoadjuvant treatment with savolitinib in METex14m-positive locally advanced primary lung adenocarcinoma, which will offer some innovative insights and clinical evidence for more effective clinical treatment of neoadjuvant targeted therapy for METex14m-positive NSCLC.

| S-EPMC9424904 | biostudies-literature

Dramatic response to neoadjuvant savolitinib in marginally resectable lung adenocarcinoma with MET exon 14 skipping mutation: A case report and literature review.

Project description:Mesenchymal-epithelial transition (MET) exon 14 skipping mutation (METex14) is a low-frequency driver mutation in metastatic non-small cell lung cancer (NSCLC) (3%-4%) and is associated with a poor prognosis. With the advent of selective MET inhibitors such as capmatinib, tepotinib, and savolitinib, the outcome for these patients was significantly improved. Here, we report a 76-year-old male patient with marginally resectable stage IIIB lung adenocarcinoma harboring METex14 who was successfully treated with savolitinib for neoadjuvant therapy. An 82% shrinkage of the primary tumor was observed, and only 5% of the tumor was viable by pathology in the following radical surgery. A dozen of studies tested the efficiency of neoadjuvant immunotherapy or immunochemotherapy, but for NSCLC with driver mutations, neoadjuvant targeted therapy might be more appropriate. We advocated the neoadjuvant MET TKI treatment for NSCLC.

| S-EPMC9646987 | biostudies-literature

MET Exon 14 Alterations in Lung Cancer: Exon Skipping Extends Half-Life.

Project description:MET exon 14 alterations are a diverse group of mutations, many of which disrupt splice acceptor or donor sites leading to exon 14 skipping, impaired receptor degradation, and oncogenic transformation. These alterations are clinically targetable with MET-directed therapy. Clin Cancer Res; 22(12); 2832-4. ©2016 AACRSee related article by Tong et al., p. 3048.

| S-EPMC4911276 | biostudies-literature

Response and acquired resistance to savolitinib in a patient with pulmonary sarcomatoid carcinoma harboring MET exon 14 skipping mutation: a case report.

Project description:BackgroundPulmonary sarcomatoid carcinoma (PSC) is a rare and poorly differentiated type of non-small cell lung cancer (NSCLC) with specific characteristics, which usually presents a challenge in clinical practice. Mesenchymal-epithelial transition (MET) gene has been identified as a promising target for treatments in the past few years. Here, we report a case of a patient with PSC harboring MET exon 14 mutation, who responded to a novel MET inhibitor - savolitinib.Case presentationA 75-year-old male patient with symptoms of cough, dyspnea and intermittent chest pain was diagnosed with sarcomatoid carcinoma. The tumor involved the right lung, the right hilum and multiple lesions in the right pleura, indicating a clinical disease stage IV. Next-generation sequencing of lung biopsy specimen indicated a MET exon 14 skipping mutation (NM_000245:c.3028+3A>G), with a variant allele frequency of 73.9%. The patient achieved a rapid and durable partial response with the initiation of savolitinib administration (600 mg, orally, once daily). The progression-free survival in this patient was 36 weeks. There were no ≥grade 3 adverse events reported and there was no dose reduction during treatment. Following savolitinib treatment, the allele frequency of MET exon 14 mutation in plasma circulating tumor DNA decreased with the reduction in tumor size. At the time of disease progression, fibroblast growth factor receptor 1 (FGFR1), EGFR and KRAS gene amplification were newly identified in tumor biopsy sample.ConclusionThis patient with PSC harboring MET exon 14 skipping mutation achieved significant clinical benefit with savolitinib treatment. Emergence of FGFR1, EGFR and KRAS gene amplification at the time of disease progression was likely responsible for the resistance to savolitinib in this case.

| S-EPMC6735656 | biostudies-literature

Long-Term Efficacy, Safety, and Subgroup Analysis of Savolitinib in Chinese Patients With NSCLCs Harboring MET Exon 14 Skipping Alterations.

Project description:IntroductionSavolitinib has been found to have encouraging antitumor activity and a favorable safety profile in Chinese patients with pulmonary sarcomatoid carcinoma and other NSCLCs with MET exon 14 skipping alterations (MET ex14 positive) at the primary analysis of a phase 2 study. Here, we present the long-term efficacy and safety data of savolitinib, including subgroup analyses.MethodsThis multicenter, single-arm, open-label, phase 2 study in the People's Republic of China enrolled MET inhibitor-naive adults with locally advanced or metastatic METex14-positive NSCLC (NCT02897479). Oral savolitinib at a dose of 400 or 600 mg was administered once daily (body weight dependent). The primary objectives of the final analysis were long-term overall survival (OS) and subgroup analyses by previous systemic treatment, NSCLC subtypes, and brain metastases.ResultsAt the final analysis cutoff date (June 28, 2021), a total of 70 patients were enrolled and receiving savolitinib, and median follow-up was 28.4 (interquartile range: 26.2-36.3) months. The median OS was 12.5 months (95% confidence interval [CI]: 10.5-21.4 [18- and 24-mo OS rates, 42.1% and 31.5%, respectively]). Median OS in pretreated or treatment-naive patients was 19.4 (95% CI: 10.5-31.3) and 10.9 (95% CI: 7.5-14.0) months, respectively; it was 10.6 months (95% CI: 4.6-14.0) in patients with pulmonary sarcomatoid carcinoma, 17.3 months (95% CI: 10.6-23.6) in other NSCLC subtypes, and 17.7 months (95% CI: 10.5-not evaluable) in patients with brain metastases. No new safety signals emerged with prolonged follow-up and exposure.ConclusionsThe updated results further confirm the favorable benefit and acceptable safety of savolitinib in Chinese patients with METex14-positive NSCLC.

| S-EPMC9547292 | biostudies-literature

MET Exon 14 Skipping in Non-Small Cell Lung Cancer.

Project description:BackgroundNon-small cell lung cancers (NSCLCs) harboring specific genetic alterations can be highly sensitive to targeted therapies.Materials and methodsWe performed a targeted rearrangement assay on 54 NSCLCs across all stages that were from patients who were never smokers and did not have driver mutations. Because MET exon 14 skipping was the most frequent alteration found, we surveyed the results for MET exon 14 skipping at Massachusetts General Hospital (MGH) since the inclusion of this alteration into our current molecular profiling panel.ResultsIn a cohort of 54 never-smokers with lung cancers that were wild-type for known driver mutations, MET exon 14 skipping was the most frequently recurring alteration, occurring in 10 cancers (19%). Clinical testing at MGH via our next-generation sequencing (NGS) and NGS-rearrangement panels showed an additional 16 cases of MET exon 14 skipping, for an overall estimated frequency of 5.6%. A clinical case of a patient with MET exon 14 skipping treated with the MET inhibitor crizotinib is also described.ConclusionMET exon 14 skipping is a targetable gene alteration found in NSCLC. Patients with these alterations may respond well to MET inhibition.Implications for practiceMET exon 14 skipping occurs with an approximately 5% frequency in NSCLC and is seen in both squamous and adenocarcinoma histology. Patients whose cancers have MET exon 14 skipping can respond well to MET inhibitors. Molecular testing for MET exon 14 skipping should be performed on all lung cancers because this is a targetable alteration.

| S-EPMC4828128 | biostudies-literature

Invasive mucinous adenocarcinoma harbored MET exon 14 skipping mutation: case report

Project description: Not available

| S-EPMC11632425 | biostudies-literature

[MET Exon 14 Skipping Mutations in Non-small Cell Lung Cancer].

Project description:Recently, targeted therapy has achieved great success in the treatment of non-small cell lung cancer (NSCLC) patients. Mesenchymal to epithelial transition factor (MET) is considered to be another important molecular target for NSCLC since epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK). Accumulating clinical trials and case reports have confirmed that MET inhibitors exhibited a potential prospect in treating patients with MET 14 exon skipping alterations, suggesting that MET 14 exon skipping mutation might be an effective biomarker for MET inhibitors, which remains to be confirmed by more clinical data. This review summarizes current research about the molecular mechanism, clinicopathological characterization, treatment strategies and drug resistance mechanisms of MET 14 exon skipping alterations in NSCLC. .

| S-EPMC6058657 | biostudies-literature

Non-small cell lung cancer with MET exon 14 skipping alteration responding to immunotherapy: a case report.

Project description:Immunotherapy has been proved to be a promising candidate for advanced non-small cell lung cancer (NSCLC). Despite MET mutations are regarded as an independent factor of programmed death ligand 1 (PD-L1) high expression, the efficacy of immune checkpoint inhibitors (ICIs) across NSCLC harboring Mesenchymal-epithelial transition factor exon 14 skipping alteration (METex14) is still uncleared. Moreover, when the resistance of PD-1 antibody occurs, the questions of how to interpret the resistance and how to overcome the resistance are worth exploring. We report a case of NSCLC with METex14 developed a right femoral metastasis after responding well to neoadjuvant immunotherapy, a successful lobectomy, and adjuvant immunotherapy. The subsequent attempts of MET targeted inhibitor, concurrent chemoradiotherapy, and notably programmed cell death protein 1 (PD-1) antibody plus vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) failed to prevent disease progression. However, a regimen of anti-PD-1 plus anti-cytotoxic t-lymphocyte associated protein 4 (CTLA-4) reversed the progression to a complete response. This case shows that METex14 had a significant response to immunotherapy, which would be especially beneficial for those who developed targeted therapy resistance. Importantly, this is the first case reporting that salvage CTLA-4 antibody and PD-1 antibody could reverse the progression in NSCLC harboring METex14 when the anti-PD-1 resistance occurred.

| S-EPMC8033371 | biostudies-literature

Current and future treatment options for MET exon 14 skipping alterations in non-small cell lung cancer.

Project description:It has been over three decades since the hepatocyte growth factor (HGF) ligand and its receptor MET proto-oncogene (MET) pathway was established as promoting cancer growth and metastasis. MET exon 14 skipping (METex14) alterations occur in 3-4% of all non-small cell lung cancer (NSCLC) patients, typically in elderly patients (older than 70 years), and result in constitutive activation of the MET receptor by altering a region required for receptor degradation. Multi-kinase inhibitor of MET, such as crizotinib, and more recently selective MET inhibitors, such as capmatinib and tepotinib, have demonstrated clinical efficacy and safety in METex14 NSCLC patients in clinical trials. These results have led to the approval of MET inhibitors by regulatory agencies across the globe. The success also fueled the excitement of further development of therapeutic strategies to target METex14 in lung cancers. This article provides an overview of the clinical development program targeting METex14 in NSCLC, including small molecular tyrosine kinase inhibitors and anti-MET antibodies. Furthermore, combination therapy immune checkpoint inhibitors or other targeted therapies are also under development in various patient populations, with acquired resistance immune or targeted therapy. Clinical trials in different development stages are ongoing and more drugs targeted to c-MET will be available for NSCLC patients with METex14 skipping mutations in the future.

| S-EPMC7890719 | biostudies-literature

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