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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Real-World Experience in Treatment of Patients with Non-Small-Cell Lung Cancer with BRAF or cMET Exon 14 Skipping
Urska Janzic1,2, Walid Shalata3, Katarzyna Szymczak4
1Department of Medical Oncology, University Clinic Golnik, 4204 Golnik, Slovenia.
Abstract:
BRAF and cMET exon 14 skipping are rare mutations of NSCLC. The treatment sequence in these cases for the first and second line is not clear. An international registry was created for patients with advanced NSCLC harboring BRAF or cMET exon 14 skipping mutations, diagnosed from January 2017 to June 2022. Clinicopathological and molecular data and treatment patterns were recorded. Data on 58 patients, from eight centers across five countries, were included in the final analysis. We found that 40 patients had the cMET exon 14 skipping mutation and 18 had the BRAF V600E mutation. In total, 53 and 28 patients received first- and second-line treatments, respectively, among which 52.8% received targeted therapy (TT) in the first line and 53.5% in the second line. The overall response rate (ORR) and disease control rate (DCR) for first-line treatment with TT vs. other treatment such as immune checkpoint inhibitors ± chemotherapy (IO ± CT) were 55.6% vs. 21.7% (p = 0.0084) and 66.7% vs. 39.1% (p = 0.04), respectively. The type of treatment in first-line TT vs. other affected time to treatment discontinuation (TTD) was 11.6 m vs. 4.6 m (p= 0.006). The overall survival for the whole group was 15.4 m and was not statistically affected by the type of treatment (19.2 m vs. 13.5 m; p = 0.83).
Insights
Targeted therapy (TT) shows superior response and longer treatment duration compared to other treatments for advanced non-small cell lung cancer (NSCLC) with BRAF or cMET exon 14 skipping mutations. Overall survival was not significantly impacted by treatment type.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- BRAF and cMET exon 14 skipping mutations are rare in non-small cell lung cancer (NSCLC).
- Optimal first- and second-line treatment sequences for these specific mutations remain unclear.
- An international patient registry was established to address this knowledge gap.
Purpose of the Study:
- To analyze treatment patterns and outcomes in advanced NSCLC patients with BRAF or cMET exon 14 skipping mutations.
- To compare the efficacy of targeted therapy (TT) versus other treatments (IO ± CT) in first-line settings.
- To evaluate factors influencing treatment discontinuation and overall survival.
Main Methods:
- An international registry collected data from January 2017 to June 2022.
- Clinicopathological, molecular, and treatment data were recorded for 58 advanced NSCLC patients.
- Patients were stratified by mutation type (cMET exon 14 skipping or BRAF V600E) and treatment received.
Main Results:
- Targeted therapy (TT) demonstrated significantly higher overall response rates (55.6% vs. 21.7%) and disease control rates (66.7% vs. 39.1%) compared to other treatments in the first line.
- TT also led to a longer time to treatment discontinuation (11.6 months vs. 4.6 months).
- Overall survival was 15.4 months and did not differ significantly between treatment groups.
Conclusions:
- Targeted therapy is associated with improved response rates and treatment durability in NSCLC with BRAF or cMET exon 14 skipping mutations.
- While TT shows benefits in response and TTD, overall survival appears unaffected by treatment modality in this cohort.
- Further research is warranted to optimize treatment strategies for these rare mutations.
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