On June 13, 2022 we conducted a systematic literature review of publications and conference abstracts reporting frequency, patient characteristics, or outcomes of patients with METex14 skipping NSCLC....In first line of treatment, median objective response rate ranged from 50.7% to 68.8% with targeted therapies (both values correspond to MET TKIs), was 33.3% with immunotherapy, and ranged from 23.1% to 27.0% with chemotherapy.

We compared the progression-free survival (PFS) of 324 advanced NSCLC patients who received ICI monotherapy (as over second-line therapy) by different AGAs....A total of 324 patients were included with the following AGAs: EGFR mutation (n = 149, 46.0%), ALK rearrangement, (n = 12, 3.7%), KRAS mutation (n = 72, 22.2%), HER2 mutation or amplification (n = 34, 10.5%), and MET ex14 skipping or amplification (n = 32, 9.9%), ROS1 rearrangement (n = 9, 2.8%), BRAF V600E (n = 9, 2.8%), and RET rearrangement (n = 7, 2.2%).....The 6-month PFS rate was 25.8% (19.5–34.3) in the group with KRAS/BRAF V600E/MET/HER2 and 12.8% (8.6–19.1) in the group with EGFR/ALK/ROS1/RET (P < 0.01)...the KRAS/BRAF V600E/MET/HER2 group had a favorable PFS compared with the EGFR/ALK/ROS1/RET group.

We identified 46 patients with MET alterations, of whom 32 had MET ex14...MET TKIs were received by 21 patients (17 crizotinib, 3 capmatinib, 1 cabozantinib), with an ORR of 29%. The median PFS with TKIs was 2.6 months (1.2-8.4)….Patients who received initial TKI (n=13) compared to those who received initial ICI (n=14) had significantly shorter OS (13.6 vs 48.3 months)...Patients with MET ex14 NSCLC benefit from ICI irrespective of PD-L1 expression and smoking history. ORR and PFS with earlier generation TKIs (crizotinib) were poor.

...43 patients with MET alterations, of whom 29 had MET ex14...Patients who received initial ICI (n = 13) compared to those who received initial TKI (n = 11) had significantly longer OS (48.3 vs 13.6 months; p = 0.005)...Patients with MET ex14 NSCLC benefit from ICI irrespective of PD-L1 expression...

Pts had advanced (stage IIIB–IV) NSCLC harboring METex14 skipping....Treatment patterns were heterogeneous across therapy lines and included available and experimental treatments (immune checkpoint inhibitor [ICI] therapy....For pts who received ICI therapy in 1L (n = 21), ORR was 33.3% (14.6, 57.0) and mPFS was 4.1 months (1.5, 8.1); in 2L (n = 10), ORR was 20% (2.5, 55.6) and mPFS was 4.1 months (1.5, 8.1).

 ICI treatment showed a high ORR and long-term efficacy for NSCLCs harboring MET exon 14 mutations.

Median overall survival for metastatic patients treated with any systemic therapy was 15.4 months….Patients with MET exon 14 skipping alteration demonstrate disease control with crizotinib, platinum-based chemotherapy and immunotherapy.

Common treatments (METex14 vs METamp) were platinum-based therapy (1st line [1L], 44 vs 41%; 2nd line [2L], 35 vs 30%) and MET inhibitor monotherapy (1L, 33 vs 29%; 2L, 30 vs 39%). Immune checkpoint inhibitors (±chemotherapy) were used across 1L (13 vs 16%) and 2L (35 vs 13%). Median (95% CI) overall survival from start of 1L therapy (any) was 12.0 months (6.8, 19.2) in METex14 and 22.0 months (9.8, 31.2) in the METamp cohort.

...69 pts with METex14 NSCLC were enrolled…Efficacy of capmatinib was demonstrated in pts who received and who did not receive prior IO: ORR 57.9% (n=11/19; 95%CI 33.5-79.7) and 34% (n=17/50; 95%CI 21.2-48.8); median DOR 11.20 months (95%CI 3.35-NE) and 7.16 months (95%CI 4.17-11.14), respectively....Capmatinib demonstrated efficacy irrespective of the prior treatment with IO, including in pts with lack of response/primary resistance to IO. Capmatinib was well-tolerated in post IO pts.

Among MET alterations, exon 14 mutations were the most sensitive to ICI….ICI has inconstant efficacy in NSCLC harboring activating mutation. KRAS, BRAF and MET-exon 14 patients derive a greater benefit than EGFR, ALK and RET patients

Adult aNSCLC patients with METex14...Median RW-PFS was 5.7 months [95% CI, 4.6-7.1] and 2.4 months [95% CI, 1.4-3.2] in patients on 1L chemotherapy (n=59) and 1L IO monotherapy (n=18), with 3-month RW-PFS rates of 78% and 33%, respectively. Median RW-PFS was 3.5 months [95% CI, 1.9-11.1] and 4.7 months [95% CI, 2.8-12.9] in patients on 2L chemotherapy (n=16) and 2L IO monotherapy (n=23), with 3-month RW-PFS rates of 54% and 67%, respectively.