Background: Patients with NSCLC harboring METex14 skipping are typically elderly with a poor prognosis, therefore treatments with a manageable safety profile are especially relevant. Tepotinib is an oral, highly selective MET TKI, approved in multiple countries for the treatment of advanced/metastatic NSCLC with METex14 skipping based on the outcomes from VISION study. Though safety outcomes and HRQoL PROs of tepotinib from VISION have previously been reported, here we report long-term safety outcomes and HRQoL PROs in patients with ≥3-year follow-up (data cut-off: May 20, 2024).
Methods: Patients with advanced EGFR/ALK wild-type NSCLC and METex14 skipping received tepotinib 500 mg (450 mg active moiety) QD until disease progression, intolerable toxicity, or withdrawal of consent. Secondary endpoints included safety and HRQoL, assessed using EORTC QLQ-C30 global health score (GHS), EQ-5D-5L visual analog scale (VAS), and EORTC QLQ-LC13 cough, dyspnea, and chest pain scores.
Results: 313 patients (median age: 72 years; ECOG 1, 73.8%) were evaluated for safety.
Safety outcomes included all-cause any grade AEs, 99.0% patients (Grade ≥3: 68.4%); any grade TRAEs, 91.7% patients (Grade ≥3: 36.1%); any grade serious TRAEs, 16.0% patients. The most common TRAE was peripheral edema, 67.7% (Grade ≥3: 11.8%).
In patients analyzed for HRQoL, mean change (±SD) from baseline for EORTC QLQ-C30 GHS was −7.1 (26.66) (n=174) and for EQ-5D-5L VAS was −10 (23.7) (n=172), with positive values indicating improvement. Similarly, EORTC QLQ-LC13 symptom scores for cough, dyspnea, and chest pain were −6.1 (28.16) (n=175), 7.1 (21.05) (n=175), and −2.3 (28.13) (n=174), respectively (negative values indicating improvement). Overall, HRQoL PROs remained stable during treatment with tepotinib.
Conclusions: Tepotinib demonstrated a continued manageable safety profile with no new safety signals, as well as stability in HRQoL PROs, consistent with earlier findings. These considerations support maximizing clinical benefits for this elderly patient population while maintaining their quality of life.