Tepotinib plus osimertinib improves overall objective response versus tepotinib alone in patients with EGFR-mutated non-small cell lung cancer (NSCLC) with MET amplification after progression on first-line osimertinib in the phase 2 INSIGHT-2 trial.
About 15–30% of patients with EGFR-mutated NSCLC treated with osimertinib develop resistance through MET amplification, which is associated with poor prognosis . The previous phase 1/2 INSIGHT trial (NCT01982955) already showed clinical activity of the selective, oral MET-inhibitor tepotinib (plus gefitinib) in patients with MET amplification and acquired resistance to previous EGFR inhibitors . Prof. Julien Mazières (CHU de Toulouse, France) presented the first findings from the current open-label phase 2 INSIGHT-2 trial (NCT03940703), which evaluated the clinical activity and safety of tepotinib plus osimertinib in this population .
The INSIGHT-2 trial enrolled 100 patients with locally advanced/metastatic EGFR-mutated NSCLC who acquired resistance to first-line osimertinib and had MET amplification. MET amplification was detected by in-situ hybridisation in tissue biopsies (MET GCN ≥5 and/or MET/CEP7 ≥2) and/or by next-generation sequencing in liquid biopsies (MET GCN ≥2.3). A total of 88 participants were treated with tepotinib (500 mg every day) plus osimertinib (80 mg every day) and 12 participants were treated with tepotinib alone. The primary endpoint was the overall response rate (ORR).
In participants treated with tepotinib plus osimertinib, ORR was 45.8% to 56.5% depending on the time of follow-up and/or MET amplification detection method. The ORR was only 8.3% in participants treated with tepotinib alone. The safety profile was consistent with the known safety profiles of tepotinib and osimertinib. Grade ≥3 adverse events were observed in 23.9% of patients treated with tepotinib plus osimertinib. Adverse events led to the discontinuation of one or both drugs in 18.2% of participants.
“Tepotinib plus osimertinib is an active oral regimen, providing a potential chemotherapy-sparing targeted therapy option for patients with EGFR-mutated NSCLC with MET amplification after progression on first-line osimertinib,” concluded Prof. Mazières.
- Koulouris A, et al. Cancers (Basel) 2022; 13: 3337.
- Wu Y-L, et al. Lancet Respir Med. 2020; 8: 1132-1143.
- Mazieres J, et al. Tepotinib + osimertinib for EGFRm NSCLC with MET amplification (METamp) after progression on first-line (1L) osimertinib: Initial results from the INSIGHT 2 study. Abstract LBA52, ESMO Congress 2022, Paris, France, 09–13 September.
Copyright ©2022 Medicom Medical Publishers
« High pathological responses in borderline resectable NSCLC patients after induction with dual immunotherapy and concurrent chemoradiotherapy Next Article
Selective KRASG12C inhibitor sotorasib demonstrates superior PFS and ORR compared to docetaxel in previously treated patients with NSCLC »
Table of Contents: ESMO 2022
Letter from the Editor
High pathological responses to neoadjuvant immune checkpoint inhibition in locally advanced dMMR colon cancer
Fruquintinib: a potential new treatment for patients with refractory mCRC
Second-line avelumab is effective in patients with MSI-H/dMMR mCRC
Upper Gastrointestinal Cancer
Deep learning models predict the risk of relapse and the mutational profile in GIST
Addition of pembrolizumab to lenvatinib does not improve OS in advanced HCC
New, highly selective inhibitor of FGFR2 driver alterations and resistance mutations
Chemo-immunotherapy in gastric cancer is more effective when administered in parallel
Tumour infiltrating lymphocytes identify patients with immunogenic triple-negative breast cancer
OS benefit of abemaciclib in HR-positive/HER2-negative advanced breast cancer not (yet) statistically significant
OS benefit of sacituzumab govitecan in pre-treated HR-positive/HER2-negative metastatic breast cancer
A pathway from air pollution to lung cancer in non-smokers identified
Selective KRASG12C inhibitor sotorasib demonstrates superior PFS and ORR compared to docetaxel in previously treated patients with NSCLC
Promising clinical activity of tepotinib plus osimertinib in NSCLC with MET amplification after progression on first-line osimertinib
High pathological responses in borderline resectable NSCLC patients after induction with dual immunotherapy and concurrent chemoradiotherapy
Treatment with tumour-infiltrating lymphocytes for advanced melanoma outperforms ipilimumab
Neoadjuvant pembrolizumab outperforms adjuvant pembrolizumab in resectable stage III–IV melanomas
Survival-benefit of neoadjuvant T-VEC maintained over 5 years of follow-up
Baseline ctDNA predicts survival in resected stage III–IV melanoma
Genitourinary Cancer – Prostate Cancer
Overall survival benefit of abiraterone in mHSPC is maintained for 7 years
Limited benefit of adding long-term ADT to post-operative radiotherapy in prostate cancer
Intensified ADT benefits biochemical progression-free survival in biochemically relapsed prostate cancer
Genitourinary Cancer – Non-Prostate Cancer
Adjuvant nivolumab plus ipilimumab does not improve survival in patients with localised RCC at high risk of relapse after nephrectomy
Triple therapy improves progression-free survival in patients with advanced RCC versus dual therapy
Adjuvant atezolizumab does not improve outcomes for patients with RCC and increased risk of recurrence
OS benefit for advanced ovarian cancer patients treated with maintenance olaparib
Maintenance tegafur-uracil does not improve survival in locally advanced cervical cancer
Head and Neck Cancer
Adding first-line pembrolizumab to CRT in locally advanced HNSCC does not significantly prolong survival or event-free survival
5-FU-free chemotherapy combination as an alternative for first-line treatment of recurrent or metastatic HNSCC
Epstein Barr virus-specific autologous cytotoxic T lymphocytes do not improve survival in nasopharyngeal carcinoma