In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 9590-9590
Abstract:
9590 Background: BRAF mutations are functionally classified into three groups, comprisingV600-mutant kinase-activating monomers (class I), kinase-activating dimers (class II), kinase-inactivating heterodimers (class III). The difference of clinical outcomes and concomitant genetic alterations among the three classes in non-small cell lung cancers (NSCLC) are unclear. Methods: We have prospectively analyzed NSCLC patients (pts) for cancer-related genes by a next-generation sequencing system, Oncomine™ Comprehensive Assay, in a large-scale genome screening project in Japan (LC-SCRUM-Japan). The clinical characteristics and outcomes of pts with BRAF-mutated non-squamous (non-sq) NSCLC were comparatively evaluated among the three classes of BRAF mutations. Results: A total of 5166 non-sq NSCLC pts were enrolled into the LC-SCRUM-Japan from 2015 to 2019. BRAF mutations were detected in 176 pts (3%). Among the 176 pts, 153 (87%) were classified into the three classes according to the mutation variants, including 65 (42%) into class I, 52 (34%) into class II and 36 (24%) into class III. The remaining 23 were not classified into any of the three classes. Compared with class I, class II or class III was significantly associated with smoking (P = 0.02 and 〈 0.01, respectively). Concomitant RAS mutations were significantly more frequent in class II and class III than in class I (P 〈 0.01 and = 0.04, respectively). The frequency of concomitant STK11 mutations was significantly higher in class III than in others (P 〈 0.01, respectively). There was no significant difference in the frequency of other oncogene and tumor suppressor gene mutations among the three classes. In the 1 st -line platinum-containing chemotherapies for advanced or recurrent cases, median progression-free survival (mPFS) of class III pts was shorter than class I or class II pts (4.2, 11.5 and 4.8 months, I vs III; P 〈 0.01, II vs III; P = 0.06). In the treatment with 2 nd -4 th line PD-1/PD-L1 inhibitors, mPFS was not significantly different among the three classes. Overall survival of class III pts was significantly shorter than class I pts (11.9 vs 35.2 months, P = 0.03). Conclusions: Concomitant gene mutations and clinical features are largely different among the BRAF mutation classes. Especially in class III, concomitant RAS and STK11 mutations are more frequent and clinical outcomes were significantly less favorable. These results suggest the need of novel therapeutic strategy based on the mutation class for BRAF-mutated lung cancers.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2020.38.15_suppl.9590
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2020
detail.hit.zdb_id:
2005181-5
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