Tepotinib Shows High Frequency of Adverse Events but Manageable Safety Profile in MET Exon 14-Altered NSCLC
核心洞察
A pooled safety analysis of 313 patients from the phase 2 VISION trial revealed that tepotinib (Tepmetko) caused adverse events in 99% of patients with MET exon 14-altered non-small cell lung cancer, though the safety profile was considered manageable.
The most common treatment-related side effect was peripheral edema, occurring in 67.7% of patients, while 37.4% of patients required at least one dose reduction during treatment.
Despite the high frequency of adverse events, patient-reported quality of life scores remained stable throughout treatment, with improvements noted in lung cancer-specific symptoms like cough and chest pain.
A comprehensive pooled safety analysis from the phase 2 VISION trial has revealed that tepotinib (Tepmetko) demonstrates a manageable safety profile despite causing adverse events in nearly all patients with MET exon 14-altered non-small cell lung cancer (NSCLC). The analysis, encompassing 313 patients from cohorts A and C, provides critical insights into the tolerability of this targeted therapy in a challenging patient population.
High Frequency of Adverse Events with Manageable Profile
The pooled safety analysis demonstrated that any-grade adverse events occurred in 99% of patients, with grade 3 or higher adverse events reported in 68.4% of patients. Treatment-related adverse events were observed in 91.7% of patients, including grade 3 or higher treatment-related adverse events in 36.1% of patients. Any-grade serious adverse events and serious treatment-related adverse events occurred in 54.6% and 16% of patients, respectively.
The impact on treatment management was substantial, with adverse events leading to dose reductions in 33.2% of patients, treatment interruptions in 43.8%, and permanent discontinuation in 15.7% of patients. Additionally, 13.7% of patients experienced an adverse event that led to death, three of which were treatment-related.
Peripheral Edema Emerges as Primary Concern
The most common treatment-related adverse effect was peripheral edema, occurring in 67.7% of patients at any grade and 11.8% at grade 3 or higher. Other frequently reported treatment-related adverse events included hypoalbuminemia (25.2% any grade; 3.8% grade 3+), nausea (23.3%; 0.6%), diarrhea (22.7%; 0.3%), and increased blood creatinine levels (22.0%; 1.3%).
Peripheral edema was also the most common treatment-related adverse event leading to dose modifications, causing dose reductions in 15.3% of patients, treatment interruptions in 18.8%, and treatment discontinuation in 6.1% of patients. In total, 37.4% of patients required at least one dose reduction during their treatment course.
Quality of Life Remains Stable Despite Adverse Events
Despite the high frequency of adverse events, health-related quality of life patient-reported outcome scores remained stable with tepotinib use. Investigators observed no meaningful change in European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) or EuroQol 5-Dimension 5-Level (EQ-5D-5L) scores up to 228 weeks.
At the end of treatment, among patients evaluated for health-related quality of life, the mean change from baseline for the EORTC QLQ-C30 global health status was −7.1, and the mean change for the EuroQol visual analogue scales was −10, with positive values signifying improvement. Notably, the mean changes from baseline in the EORTC QLQ-lung cancer symptom scores showed improvement for cough (−6.1) and chest pain (−2.3), while dyspnea showed a slight worsening (7.1), with negative values signifying improvement.
The median time to deterioration of lung cancer-specific symptoms varied considerably: 36.5 months for cough, 30.4 months for chest pain, and 5.5 months for dyspnea.
Trial Design and Patient Population
The VISION trial was a single-arm study evaluating tepotinib at a dose of 500 mg orally once daily in patients with advanced NSCLC harboring MET exon 14 skipping alterations. Eligible patients were at least 18 years of age with histologically or cytologically confirmed NSCLC and MET exon 14 skipping alterations detected by liquid biopsy and/or tissue biopsy.
The study population had a median age of 72 years, with 50.8% being female and 73.8% having an ECOG performance status of 1. At study entry, 47.6% of patients had received at least one prior systemic therapy. The median treatment duration was 7.5 months, with 19 patients remaining on tepotinib for at least 48 months.
"Throughout the VISION trial, patients completed questionnaires evaluating their quality of life before and while receiving tepotinib," explained Dr. Enriqueta Felip, lead study author and head of the Thoracic Cancer Unit at Hospital Universitari de la Vall d'Hebron (搜索) in Barcelona, Spain. "Overall, patients reported that health and quality of life remained stable while receiving tepotinib. Specific scores relating to symptoms experienced by patients with lung cancer were improved during treatment for symptoms such as cough and chest pain and remained stable for shortness of breath."