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Matching-Adjusted Indirect Comparison (MAIC) of Tepotinib with Other MET Inhibitors for the Treatment of Advanced
Paul K Paik1, Boris M Pfeiffer2, Helene Vioix3
1Memorial Sloan Kettering Cancer Center, New York, USA.
Introduction:
MET exon 14 skipping in patients with advanced non-small cell lung cancer (aNSCLC), can be targeted with MET inhibitors including tepotinib, capmatinib, savolitinib, and crizotinib. Matching-adjusted indirect comparison (MAIC) methodology was used to compare outcomes data between agents and to address bias from differences in baseline characteristics.
Methods:
Patient-level data from the VISION study (tepotinib) were weighted for comparison with aggregate data from the GEOMETRY mono-1 (capmatinib), NCT02897479 (savolitinib) and PROFILE 1001 (crizotinib) studies in patients with aNSCLC, using baseline characteristics prognostic for overall survival (OS) in VISION. Overall response rate (ORR), OS, progression-free survival (PFS), and duration of response (DOR) were compared. Patients were stratified by line of therapy: overall (all lines), previously treated, and treatment-naïve.
Results:
Improvements in ORR and all time-to-event endpoints were predicted for tepotinib compared with crizotinib and savolitinib in the different populations, although comparisons with savolitinib were hindered by considerable differences in baseline patient populations. Tepotinib appeared to be associated with prolonged PFS and OS compared with capmatinib in previously treated patients (PFS HR 0.54; 95% CI 0.36-0.83; OS HR 0.66; 95% CI 0.42-1.06) and the overall populations (PFS HR 0.60; 95% CI 0.43-0.86; OS HR 0.72; 95% CI 0.49-1.05), with smaller improvements in DOR. The ORR comparisons between tepotinib and capmatinib identified a swing of up to ± 6 percentage points in the weighted tepotinib ORR depending on the population studied (treatment-naïve vs. previously treated patients).
Conclusions:
The MAIC identified potential differences in efficacy endpoints with the different MET inhibitors, and predicted prolonged PFS and OS with tepotinib compared with capmatinib and crizotinib. Although MAIC cannot balance for unobserved factors, it remains an informative method to contextualize single-arm studies, where head-to-head trials are unlikely to be feasible.
Insights
MET exon 14 skipping mutations in advanced non-small cell lung cancer can be targeted by several MET inhibitors. Tepotinib showed potential for improved progression-free survival and overall survival compared to capmatinib and crizotinib in a matching-adjusted indirect comparison analysis.
Area of Science:
- Oncology
- Pharmacology
Background:
- MET exon 14 skipping mutations are a targetable driver in advanced non-small cell lung cancer (aNSCLC).
- Several MET inhibitors, including tepotinib, capmatinib, savolitinib, and crizotinib, are available for treating aNSCLC with MET exon 14 skipping.
- Direct head-to-head clinical trials comparing these agents are limited, necessitating indirect comparison methods.
Purpose of the Study:
- To compare the efficacy of tepotinib against other MET inhibitors (capmatinib, savolitinib, crizotinib) in patients with aNSCLC harboring MET exon 14 skipping alterations.
- To utilize matching-adjusted indirect comparison (MAIC) methodology to account for baseline characteristic differences between patient populations in single-arm studies.
Main Methods:
- Patient-level data from the tepotinib VISION study were weighted to match aggregate data from capmatinib (GEOMETRY mono-1), savolitinib (NCT02897479), and crizotinib (PROFILE 1001) studies.
- Comparisons were stratified by line of therapy: overall, previously treated, and treatment-naïve.
- Key efficacy endpoints assessed included overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and duration of response (DOR).
Main Results:
- Tepotinib demonstrated predicted improvements in ORR and time-to-event endpoints compared to crizotinib and savolitinib.
- Tepotinib was associated with prolonged PFS and OS compared to capmatinib in both previously treated and overall patient populations (PFS HRs ranging from 0.54-0.60; OS HRs ranging from 0.66-0.72).
- Overall response rate comparisons between tepotinib and capmatinib showed variability (±6 percentage points) based on patient population.
Conclusions:
- The MAIC analysis suggests potential differences in efficacy among MET inhibitors for aNSCLC with MET exon 14 skipping.
- Tepotinib is predicted to offer prolonged PFS and OS relative to capmatinib and crizotinib.
- MAIC is a valuable method for contextualizing single-arm study data when head-to-head trials are not feasible.
