What is the role of Capmatinib (generic name: capmatinib) in improving survival outcomes for patients with non-small cell lung cancer (NSCLC) with MET exon 14 skipping mutations?

Capmatinib in MET Exon 14-Mutated Non-Small Cell Lung Cancer: Survival Outcomes

Capmatinib significantly improves survival outcomes in patients with non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations, with first-line therapy showing a median progression-free survival of 12.4 months and an overall response rate of 68%. 1

Efficacy of Capmatinib in MET Exon 14-Mutated NSCLC

First-Line Treatment

• Overall response rate: 68% (95% CI 55.0-79.7) in treatment-naïve patients 2
• Median progression-free survival (PFS): 12.4 months 1
• Median duration of response: 12.6 months 1, 3
• Effective against brain metastases with 54% response rate (including 4 complete responses in brain lesions) 1

Second-Line or Later Treatment

• Overall response rate: 41-44% in previously treated patients 1, 2, 3
• Median PFS: 5.4 months 1
• Median duration of response: 9.7 months 1, 3

Clinical Recommendations

The National Comprehensive Cancer Network (NCCN) Guidelines (2024) recommend:

1. First-line therapy options for MET exon 14 skipping mutation:

   • Capmatinib (preferred) 1
   • Tepotinib (preferred) 1
   • Crizotinib (useful in certain circumstances) 1

2. Subsequent therapy options:

   • Capmatinib or tepotinib if not previously used 1
   • Switching between agents with similar mechanism of action at progression is NOT recommended 1

Survival Impact

While specific overall survival data is limited in the guidelines, a retrospective analysis showed:

• Median overall survival of 21.5 months for capmatinib-treated patients with MET exon 14 skipping mutations or high MET gene copy number (≥10) 4
• Median overall survival of only 7.5 months for similar patients who did not receive capmatinib 4

This demonstrates a significant survival advantage with capmatinib treatment in this population.

Safety Profile

Common adverse events include:

• Peripheral edema (47-51% of patients) 1, 3
• Nausea (35-45%) 1, 3
• Increased blood creatinine (21%) 1
• Vomiting (20%) 1

Most adverse events are grade 1-2 in severity. Serious adverse events (grade 3-4) occurred in 44% of patients, with dyspnea being most common (5%) 2. Treatment-related deaths are rare (reported in approximately 1% of patients) 1, 2.

Important Clinical Considerations

1. Patient Selection:

   • MET exon 14 skipping mutations occur in 3-4% of adenocarcinoma NSCLC and 1-2% of other NSCLC histologies 1
   • Testing for MET exon 14 skipping mutations should be part of broad molecular profiling 1

2. Brain Metastases:

   • Capmatinib has demonstrated efficacy in patients with brain metastases 1
   • Consider that 43% of responding patients with brain metastases had previously received radiation therapy 1

3. Treatment Sequencing:

   • Immune checkpoint inhibitor monotherapy may be less effective in NSCLC with MET alterations 1
   • For patients who progress on capmatinib, other systemic therapy regimens (chemotherapy with or without immunotherapy) are recommended 1

4. Monitoring:

   • Regular monitoring for peripheral edema, nausea, and vomiting is essential 1
   • Liver function tests should be monitored due to rare but serious hepatic adverse events 2

Capmatinib represents a significant advance in targeted therapy for NSCLC patients with MET exon 14 skipping mutations, offering meaningful improvements in survival outcomes and quality of life compared to conventional therapies.