Real-world experience with capmatinib in <i>MET</i> exon 14-mutated non-small cell lung cancer (RECAP): a retrospective analysis from an early access program

Illini, Oliver; Fabikan, Hannah; Swalduz, Aurélie; Vikström, Anders; Krenbek, Dagmar; Schumacher, Michael A.; Dudnik, Elizabeth; Studnicka, Michael; Öhman, R.; Wurm, Robert; Wannesson, Luciano; Peled, Nir; Kian, Waleed; Bar, Jair; Daher, Sameh; Addeo, Alfredo; Rotem, Ofer; Pall, Georg; Zer, Alona; Saad, Akram; Čufer, Tanja; Sorotsky, Hadas; Hashemi, S.; Mohorcic, Katja; Stoff, Ronen; Rovitsky, Yulia; Keren-Rosenberg, Shoshana; Winder, Thomas; Weinlinger, Christoph; Valipour, Arschang; Hochmair, Maximilian

doi:10.1177/17588359221103206

Cited by 21 publications

(25 citation statements)

References 32 publications

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“… 10 A recent real-world study on the early access program of capmatinib also reported intracranial RR of 46% and disease control rate of 91%, comparable with the previous phase 2 trial results. 21 These data suggest the possible CNS activity of the novel MET inhibitors. A current international guideline recommends capmatinib for MET exon 14-positive NSCLC patients with brain metastasis.…”

Section: Discussionmentioning

confidence: 85%

Capmatinib in MET Exon 14 Skipping Mutation-Positive Lung Adenocarcinoma with Extensive Central Nervous System Metastasis

Kim¹,

Lee²,

Lee³

2022

OTT

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Several selective mesenchymal–epithelial transition (MET) inhibitors have recently demonstrated favorable systemic efficacy in MET exon 14 skipping mutation-positive non-small cell lung cancer. However, there are limited data on their efficacy against central nervous system (CNS) metastasis, especially leptomeningeal seeding. Recently, we encountered a case of a 65-year-old woman who was diagnosed with metastatic lung adenocarcinoma. As routine molecular testing showed no genomic alterations, including epidermal growth factor receptor mutation and anaplastic lymphoma kinase translocation, the patient received a frontline platinum-doublet followed by paclitaxel. However, the tumor did not respond to these therapies, and her condition became deleterious owing to extensive brain and leptomeningeal metastases. Plasma genotyping revealed that the tumor harbored a MET exon 14 skipping mutation, and we started capmatinib, a selective MET inhibitor. The CNS lesions markedly decreased and the performance status of the patient dramatically improved. Our report highlights the significant CNS activity of capmatinib, even in cases of leptomeningeal metastasis. In addition, this report emphasizes the importance of the active utilization of molecular profiling to detect rare but druggable genetic alterations for the better management of patients with lung cancer.

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Section: Discussionmentioning

confidence: 85%

Capmatinib in MET Exon 14 Skipping Mutation-Positive Lung Adenocarcinoma with Extensive Central Nervous System Metastasis

Kim¹,

Lee²,

Lee³

2022

OTT

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“…In a preplanned analysis of Japanese patients enrolled in GEOMETRY mono-1 ( n = 45), peripheral edema was the second most frequent treatment-related AE, occurring in 31% of patients [ 25 ]. More recently, real-world data from an international early access program study of capmatinib in 81 patients with advanced METex14 -mutated NSCLC found that peripheral edema was the most common treatment-related AE of any grade (48%) or Grade ≥ 3 (13%) [ 26 ].…”

Section: Incidence Of Peripheral Edema In Clinical Trialsmentioning

confidence: 99%

“…More recently, real-world data from an international early access program study of capmatinib in 81 patients with advanced METex14 -mutated NSCLC found that peripheral edema was the most common treatment-related AE of any grade (48%) or Grade ≥ 3 (13%) [ 26 ].…”

Section: Incidence Of Peripheral Edema In Clinical Trialsmentioning

confidence: 99%

“…In a Phase II Chinese study in patients with METex14 skipping NSCLC (n = 70), peripheral edema was the most common treatment-related AE of any grade (54%) or Grade ≥ 3 (9%) with savolitinib (400 or 600 mg once daily) [32]. [24] Any 21% GEOMETRY mono-1 Phase II study (NCT02414139) [12] Any 51% Treatment-related 43% GEOMETRY mono-1: Japanese patients [25] Treatment-related 31% Early access program [26] Treatment-related 48%…”

Section: Incidence Of Peripheral Edema In Clinical Trialsmentioning

confidence: 99%

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Management of Peripheral Edema in Patients with MET Exon 14-Mutated Non-small Cell Lung Cancer Treated with Small Molecule MET Inhibitors

et al. 2022

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Small molecule mesenchymal-epithelial transition (MET) inhibitors, such as crizotinib, capmatinib, and tepotinib, are treatment options for metastatic non-small cell lung cancer (NSCLC) in adult patients whose tumors have a mutation that leads to MET exon 14 skipping. In clinical trials, these MET inhibitors were associated with a high incidence of peripheral edema, although this was generally mild-to-moderate in severity. There is limited information about the mechanism involved in MET inhibitor-induced peripheral edema. Perturbation of hepatocyte growth factor (HGF)/MET signaling may disrupt the permeability balance in the vascular endothelium and thus promote edema development. Another potential mechanism is through effects on renal function, although this is unlikely to be the primary mechanism. Because edema is common in cancer patients and may not necessarily be caused by the cancer treatment, or other conditions that have similar symptoms to peripheral edema, a thorough assessment is required to ascertain the underlying cause. Before starting MET-inhibitor therapy, patients should be educated about the possibility of developing peripheral edema. Patient limb volume should be measured before initiating treatment, to aid assessment if symptoms develop. Since the exact mechanism of MET inhibitor-induced edema is unknown, management is empiric, with common approaches including compression stockings, specific exercises, massage, limb elevation, and/or diuretic treatment. Although not usually required, discontinuation of MET inhibitor treatment generally resolves peripheral edema. Early diagnosis and management, as well as patient information and education, are vital to decrease the clinical burden associated with edema, and to reinforce capmatinib treatment adherence.

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“…Their OS is comparable to that of patients with undetected major driver mutations ( 16 ). Although MET ex14-positive NSCLC patients treated with selective MET TKIs reported longer OS, up to 30%-40% of these patients were reported to be non-responders ( 11 , 17 , 18 ). The factors associated with a poor prognosis in these patients remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Survival outcomes and prognostic factors of lung cancer patients with the MET exon 14 skipping mutation: A single-center real-world study

Gow

Hsieh²,

Chen³

et al. 2023

Front. Oncol.

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IntroductionThe MET exon 14 skipping (METex14) mutation is an important oncogenic driver in lung cancer. We performed a retrospective analysis of clinical data from lung cancer patients with the METex14 mutation to analyze their survival outcomes and associated prognostic factors.MethodsA one-step reverse transcription-polymerase chain reaction to examine the presence of the METex14 mutation was performed using RNA samples from 1374 lung cancer patients with no detected EGFR and ALK mutations. Pathological features and immunohistochemistry (IHC) results for c-MET were analyzed in patients with METex14-positive tumors.ResultsMETex14 was identified in 69 patients with lung cancer, including 53 adenocarcinoma (ADC) and 16 non-ADC patients. In comparison with patients without the METex14 mutation, lung cancer patients harboring the METex14 mutation were generally elderly individuals, never-smokers, and had poor performance scores. A higher frequency of METex14 mutations was detected in pulmonary sarcomatoid carcinoma (PSC) patients (24.3%, n = 9/37). However, stage IV PSC patients with or without the METex14 mutations showed similarly poor overall survival (OS) (p = 0.429). For all 36 METex14-positive lung ADCs, multivariate analysis showed several poor prognostic factors, including strong c-MET IHC staining (p = 0.006), initial brain metastasis (p = 0.005), and administration of only supportive care (p < 0.001). After excluding seven patients who received only supportive care, we further analyzed 29 stage IV lung ADC patients with METex14 mutations who received anti-cancer treatment. Multivariate analysis showed that pemetrexed treatment (p = 0.003), lung radiotherapy (p = 0.020), initial brain metastasis (p = 0.005), and strong c-MET IHC staining (p = 0.012) were independent prognostic factors for OS in these patients.ConclusionsA higher frequency of METex14 mutations was detected in PSC patients. Stage IV PSC patients with or without the METex14 mutations had similarly poor overall survival. Pemetrexed-based chemotherapy, strong c-MET ICH staining, initial brain metastasis, and lung radiotherapy, may help predict survival outcomes in patients with advanced lung ADCs harboring the METex14 mutation.

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Real-world experience with capmatinib in MET exon 14-mutated non-small cell lung cancer (RECAP): a retrospective analysis from an early access program

Cited by 21 publications

References 32 publications

Capmatinib in MET Exon 14 Skipping Mutation-Positive Lung Adenocarcinoma with Extensive Central Nervous System Metastasis

Capmatinib in MET Exon 14 Skipping Mutation-Positive Lung Adenocarcinoma with Extensive Central Nervous System Metastasis

Management of Peripheral Edema in Patients with MET Exon 14-Mutated Non-small Cell Lung Cancer Treated with Small Molecule MET Inhibitors

Survival outcomes and prognostic factors of lung cancer patients with the MET exon 14 skipping mutation: A single-center real-world study

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