Introduction: BRAF mutations occur 1%-4% in nonesmall-cell lung cancer, and the natural history of tumors harboring these mutations remains an area of ongoing study. The aim of this retrospective study was to describe the natural history, occurrence of co-mutations and clinical outcomes in patients with BRAF-mutated NSCLC. Methods: Patients with BRAF-mutated NSCLC seen at Affiliated cancer hospital of Zhengzhou university from January 1, 2017 through December 31, 2019 were reviewed. The Kaplan-Meier method was used to calculate median progression free survival (PFS) and median overall survival, and the COX regression model was established to analyze the association between the overall survival and various factors. Results: NGS (Next Generation Sequencing) data of either plasma or tissue samples obtained from 3217 Chinese stage I-IV NSCLC patients were retrospectively analyzed, 46 (1.4%) patients were found to have BRAF mutation, including 35(76%) V600E mutation and 11non-V600E mutation. Concomitant mutations had been also discovered, it's a more tendency for V600E mutation to had a concomitant mutation, Among 35 NSCLC with V600E mutation, 2 had a concomitant mutation in EGFR 19 exon deletion,1 in EGFR 21exon L858R mutation,1 inTP53 mutation and 1 in PIK3CA mutation; However, in the 11 non-V600E mutation, no concomitant mutation was found, but 2 with MET amplification. Clinical and pathological features were similar between patients with V600E vs non-V600E mutations.The average age was 62 years old ( 43-84). 25(54%) males and 27(58%) never smoker, 3(7%) light smoker and 16(35%) heavy smoker. The vast majority (93%,43/46) of pathological type was adenocarcinoma, other types including 1 squamous carcinoma and 2 with difficult histological classification. 42 were advanced stage at diagnosis, while 4 were early stage. The common metastasis sites was lung, pleural effusion, liver and adrenal gland. Retroperitoneal lymph node metastasis was also found frequently (17%,8/46). In the advanced and recurrent NSCLC with BRAF mutation, 25 patients had detailed treatment record and follow up information. Most (20/25) of them had chose chemotherapy ± bevacizumab as first line, while the rest accepted other treatment, including 1 chemotherapy combined with pembrolizumab, 3 Icotinib and 1 vandetanib. The Overall Response Rate (ORR) of first line was 44% (11/25) and median PFS was 8.67m(6.9m-10.5m). After disease progress, nearly half (11/25) of the patients accepted second line treatment, 3 had pembrolizumab, 3 enrolled in clinical trials, and others accepted chemotherapy or antiangiogenesis drugs. The ORR of second line was 14.3% (2/14) and median PFS was 5.1m(2.2m-8.0m). At the data cutoff of follow-up (July 31, 2020), OS events were 11 (44%), and median OS was 33.9m(3.2m-64.7m). Conclusion: The most common genotype of NSCLC with BRAF mutation was V600E mutation, which was more tendency to have a concomitant mutation, the therapeutic response was well, and overall survival data had showed a promising outcomes.
Uncommon EGFR mutations were observed in 38 patients, comprising approximately 10% of all EGFRmut + NSCLC patients (348) diagnosed and treated in Alberta, Canada (2010-2017. Of the total 38 patients, 63% were female, 60% had a smoking history, and 75% were Canada-born. Dual/-triple mutation positivity was found in 40% of patients. 4/38 patients expired prior to receiving any form of palliative treatment. Upon classifying patients as per TKI treatment, it was found that most received gefitinib (67%) as first line systemic palliative treatment (Table 2). Median OS of the entire cohort was 15.1 months; meanwhile those with complex double/-triple mutations experienced longer mOS of 24.9months vs 11.8months for single uncommon carriers. Conclusion: This Canadian study supports that uncommon EGFR mutation carriers are infrequent in clinical lung cancer practice. Of note, they represent a unique sub-population amongst EGFRmut + NSCLC patients, and experience differential sensitivity and varied responses to treatment. We observed favorable responses to EGFR-TKIs in patients with double/-triple uncommon mutations, supporting that these patients may benefit from EGFR-TKIs.
3039 Background: Molecular profiling of tumor tissue is the gold standard for treatment decision making in advanced non-small cell lung cancer. Results may be delayed or unavailable due to insufficient tissue samples or prolonged wait times for biopsy, pathology assessment and testing. We piloted the use of plasma molecular testing as part of the initial diagnostic work-up for patients with suspected advanced lung cancer (NCT04863924). Methods: Patients with radiologic evidence of advanced lung cancer referred to the lung rapid diagnostic program underwent plasma circulating tumor DNA (ctDNA) testing using InVisionFirst-Lung, a next-generation sequencing (NGS) assay targeting 37 genes. Standard tissue testing was performed with comprehensive NGS (Oncomine). The primary endpoint was time to treatment in stage IV NSCLC patients compared to an historical pre-COVID-19 cohort (2018-9). Secondary endpoints included actionable targets identified in plasma, % of patients starting targeted therapy based on liquid biopsy and result turnaround time (TAT). Results: Between July 1 to December 31, 2021, 60 patients were enrolled. Median age was 70 years (range 33-91), 52% were female, 57% Caucasian, 48% never smokers. Of these, 73% had NSCLC, 12% small cell, 10% non-lung pathology and 5% declined tissue biopsy. Of 44 NSCLC patients, 5 (11%) had early-stage disease and underwent curative therapy. Most stage IV patients (79%) had systemic treatment. Median time to treatment initiation in the study cohort was 34 days (n = 31, range 10-90) versus 62 days (n = 101, range 13-159) in the historical cohort (p<0.0001). Two thirds (N = 23) of stage IV NSCLC patients had actionable alterations identified, (30% in current/ex-smokers); 18 started targeted therapy including 10 based on plasma results before tissue results were available. Median TAT was 7 days for plasma from blood draw to reporting (range 4-14) and 26 days for tissue molecular testing (range 11-42), p<0.0001. Concordance was high between plasma and tissue testing (70%). Liquid biopsy identified actionable alterations for 3 patients not identified by tissue NGS. In 4 cases, plasma testing failed to identify actionable alterations detected in tissue, due to undetectable plasma ctDNA. Conclusions: Liquid biopsy in the initial diagnostic workup of patients with suspected advanced NSCLC leads to faster molecular results and shortens time to treatment compared to tissue testing alone. Supplementing the current standard of tissue molecular testing with a plasma-first approach during the diagnostic work up of patients with suspected advanced lung cancer may increase access to precision medicine and improve patient outcomes. Clinical trial information: NCT04863924. [Table: see text]
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