Patients and MethodsĪs reported previously ( 9), this study was prematurely terminated due to difficulties identifying patients meeting eligibility criteria hence, all analyses should be considered exploratory.
FINAL DRAFT FREE TRIAL UPDATE
Here, we report the final analyses from phase II of the INSIGHT trial, after an extended duration of follow-up, with a focus on patients with MET amplification and an update on patients with high MET overexpression.
FINAL DRAFT FREE TRIAL PLUS
In patients with MET amplification, median PFS was 16.6 versus 4.2 months, median OS was 37.3 months versus 13.1 months (HR, 0.08 90% CI, 0.01–0.51), objective response rate (ORR) was 67% versus 43%, and median duration of response (DOR) was 19.9 versus 2.8 months with tepotinib plus gefitinib versus chemotherapy, respectively ( 9).
However, substantial improvements in progression-free survival (PFS) and overall survival (OS) were seen in the preplanned subgroup analysis of patients with high MET overexpression or MET amplification ( 9). In the 18-month follow-up analysis (data cut-off: Decemmedian follow-up: 21.8 months), no significant difference was observed in the overall population, in which 38% of patients had moderate MET overexpression.
FINAL DRAFT FREE TRIAL TRIAL
The phase Ib/II INSIGHT trial evaluated tepotinib plus gefitinib versus chemotherapy in patients with EGFR-mutant NSCLC who had progressed on an EGFR TKI due to MET amplification or moderate (IHC 2+) or high (IHC 3+) MET overexpression ( 9).
Tepotinib is also being investigated in combination with EGFR TKI therapy in EGFR-mutant MET-amplified NSCLC ( 6, 9). In this setting, tepotinib has demonstrated robust and durable clinical activity, with a manageable safety profile ( 15–17). Tepotinib, a once-daily and highly selective MET TKI, is approved in multiple countries for the treatment of patients with NSCLC with MET exon 14 ( METex14) skipping. Tepotinib plus an EGFR inhibitor is a promising strategy in this disease setting. Furthermore, all patients who received long-term tepotinib plus gefitinib had MET amplification, with 25% of patients with MET amplification receiving combination treatment for >4 years, and 17% for >5 years (including continuing treatment outside the study). This long follow-up emphasizes that the greatest benefit from tepotinib plus gefitinib is derived by patients with MET amplification, who showed substantially improved progression-free and overall survival versus chemotherapy in this updated analysis. We present final analyses from the phase II part of INSIGHT, evaluating tepotinib (a once-daily, highly selective MET inhibitor) plus gefitinib versus chemotherapy in patients with EGFR-mutant NSCLC and MET-driven EGFR inhibitor resistance, with a median follow-up duration of 57.5 months. There is a high unmet need for patients with EGFR-mutant non–small cell lung cancer (NSCLC) that have developed resistance to EGFR inhibitors.
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