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Found 1 Presentation For Request "1968p"
1968P - The clinical effect of concurrent oncogenic gene mutations in BRAF p.(V600E)-mutated NSCLC treated with dabrafenib and trametinib
- Pei Meng (Groningen, Netherlands)
Abstract
Background
Combined dabrafenib and trametinib treatment of advanced non-small cell lung cancer (NSCLC) patients harboring BRAF p.(V600E) mutations results in an overall response rate of about 60%. However, the duration of response is limited and variable. It is still unknown whether co-occurring gene mutations confer resistance to the dual BRAF and MEK inhibition therapy.
Methods
Samples from 36 advanced NSCLC patients before dabrafenib and trametinib treatment were included. The most common clinically relevant hotspot mutations in lung cancer were tested by targeted next generation sequencing for treatment decision making. Progression-free survival (PFS) data were collected from the clinical records.
Results
A BRAF p.(V600E) was identified in 35 patients and a p.(V600_K601delinsE) was observed in one patient. Concurrent oncogenic mutations were observed in 8 of the 36 patients, involving the mTOR pathway (PIK3CA and AKT1) in 4 patients, MAPK/ERK pathway (BRAF non-V600E), KIT in one patient, IDH1 in 2 patients, and GNAS in one patient. Patients with and without concurrent mutations had a PFS of 20.3 and 10.2 months, respectively. Log-rank analysis showed no significant difference, P=0.58. The patient with a BRAF p.(V600_K601delinsE) responded to the treatment and had a PFS of 5 months. The patient that had a concurrent BRAF p.(G466V) and KIT p.(K509Q) mutations had a stable disease for only 3 months. Patients with a concurrent PIK3CA p.(G1049R) or AKT1 p.(E17K) mutation had a relatively short PFS of 4 and 3 months, respectively. Two patients with a concurrent PIK3CA p.(H1047R) mutation had an ongoing response of 54 and 57 months. The two patients with a concurrent IDH1 p.(R132C) mutation had a complete response with a PFS of 32 months and an ongoing response of 12 months. The patient with a GNAS p.(R201C) had a PFS of 8 months.
Conclusions
There was no difference for PFS between patients with and without concurrent mutations as assessed by our diagnostic NGS panel. Further analysis by whole exome sequencing needs to be done on a larger cohort, to establish whether additional mutations in other pathways cause resistance to dabrafenib/trametinib.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.