Tepotinib Compared With Chemoimmunotherapy in First-Line Non-Small Cell Lung Cancer (NSCLC): Matching Adjusted Indirect Comparison (MAIC) of VISION in MET Exon 14 (METex14) Skipping NSCLC and KEYNOTE-189 in Wild-type NSCLC

OBJECTIVES:

Tepotinib is approved in multiple countries for METex14 skipping NSCLC based on the single-arm Phase II VISION trial (NCT02864992). Prior to approval, patients with this oncogenic driver were treated first-line with chemoimmunotherapy (C+IO), but no study is available for C+IO in patients with METex14 skipping. Therefore, a MAIC was conducted to understand comparative effectiveness.

METHODS:

The MAIC (implemented using the R ‘maic’ package) reweighted patient-level data from the VISION February 2021 cut-off in treatment-naïve METex14 skipping patients to match published patient characteristics in the protocol-specified final analysis from KEYNOTE-189 (pembrolizumab + platinum doublet-chemotherapy in non-squamous, wild-type NSCLC). Studies were matched on age, sex, ECOG, smoking history, histology, and disease stage. Patient characteristics, progression-free survival (PFS) and overall survival (OS) were compared between adjusted-VISION and KEYNOTE-189.

RESULTS:

Differences were observed at baseline between VISION and KEYNOTE-189 populations, including age (median 73.8 vs 65.0 years), ECOG-0 (27.7% vs 45.1%), and smoking history (54% vs 88%). These differences were resolved after matching, reducing the VISION effective sample size (148 to 38.7). Unweighted median (m) PFS was identical between studies, C+IO 11.9 months (95% CI: 8.4, 10.9) vs. tepotinib 11.9 months (95% CI: 7.1-12.4). After weighting, tepotinib was favored (mPFS 14.6 months; 95% CI: 10.1, not reached), with a weighted Cox proportional hazard ratio of 0.67 (95% CI: 0.42, 1.07; p=0.091). Consistent OS results were observed (mOS: C+IO 22.3 months vs tepotinib 23.6 months).

CONCLUSIONS:

Following population balancing based on patient characteristics, tepotinib appeared to have a greater PFS than C+IO. However, uncertainty exists due to differences in patient characteristics between METex14 skipping and wild-type NSCLC and the lack of matching on PD-L1 or METex14 skipping. Previous studies suggest METex14 skipping is a negative prognostic factor for IO treatments, so the advantage of tepotinib compared with C+IO could be greater in this population.