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Poster Session (ID 8)
- Event: ACLC 2018
- Type: Poster Session
- Presentations: 2
- Coordinates: 11/07/2018, 00:00 - 00:00, Poster Hall
P020 - Characterization of Met Exon 14 Skipping and Association with Clinical Outcomes of Crizotinib in Chinese Lung Cancers (ID 192)
00:00 - 00:00 | Author(s): P. Chen
Mesenchymal-to-epithelia transition (MET) exon 14 skipping (METex14) has been recognized as a potential driver alteration in lung cancers, and represents an emerging molecular target for lung cancer treatment. However, most studies about patient characterization and clinical outcomes of METex14-positive lung cancer were conducted in Caucasians, relevant data in Chinese patients were lacking. Here, we retrospectively characterized the clinical and molecular features of patients harboring MET mutations causing exon 14 skipping in a large cohort of Chinese lung cancers, and interrogated relevant clinical parameters associated with clinical outcomes of crizotinib treatment.
Genomic profiling data obtained from either plasma or tissue of 7,507 lung cancer patients with various histological types were screened to identify patients harboring METex14.
A total of 68 patients (0.91%), different from the frequency of Western population (3%), were identified to carry DNA alterations predicted to cause METex14 with a median age of 67.5, which is statistically significantly older than the whole cohort (p<0.001, t-test). In addition, METex14 has a female predominance (p=0.036, Fisher
P071 - Variants Distribution and Heterogeneity of Outcomes to Crizotinib in ALK-Rearranged Chinese Non-Small Cell Lung Cancers (ID 179)
00:00 - 00:00 | Author(s): P. Chen
ALK-rearranged NSCLC is a unique molecular subgroup with high sensitivity to ALK inhibitors. Crizotinib, a FDA-approved tyrosine kinase inhibitor for ALK-rearranged NSCLCs, showed remarkable response in ALK-positive NSCLC. However, the magnitude and duration of clinical responses to crizotinib among different ALK variants are found to be heterogeneous, and studies about the clinical outcomes showed contradict conclusions.
We collected sequencing information from 110 ALK-positive Chinese NSCLC patients, whose tissue or plasma biopsies were sequenced in a CLIA-certified genomic profiling laboratory. Sequencing results were reviewed with the intent of studying ALK rearrangement distribution and clinical outcomes to crizotinib.
A total of 134 (5.6%) ALK rearrangements were identified in a cohort of 1971 NSCLCs, with 39 unique rearrangement partners. EML4 was the most common ALK rearrangement partner, with variant 3 (v3) as the most frequent variants (42.7%) of EML4-ALK fusion, accounting for 71.6% (96/134) of all the rearrangements in 87.3% (96/110) patients. For EML4-ALK positive patients after crizotinib treatment (n=96), survival analysis revealed that patients with EML4-ALK only displayed favorable PFS (10.0 vs 7.2 months, p=0.037) and OS (36.0 vs 20.0 months, p=0.037) than those combined with other fusions. In vitro data reported that variant v3 and v5 was structurally stable and less sensitive to ALK inhibitors due to the lack of TAPE domain. In this study, patients harboring v3 and v5 displayed significantly inferior OS than those with other variants (31 vs 37.6 months, p=0.010). For all the ALK-rearranged patients (n=110), no significant difference was observed between the survival of EML4-ALK and non-EML4-ALK (PFS, 9.4 vs 14.5 months, p=0.61; OS, 35.1 vs 35.5 months, p=0.58), below and above 40-years (PFS, 7.3 vs 11.3 months, p=0.23; OS, 25.4 vs 35.5 months, p=0.69).
This study demonstrated the distribution pattern of ALK rearrangements in Chinese NSCLCs, and illustrated the clinical outcomes of ALK-positive patients in different sub-groups. We hope this study could improve basic knowledge of ALK rearrangement and might be helpful for clinicians in choosing patients for appropriate medical treatment. Moreover, these findings advocate for more comprehensive ALK genomic profiling and validation of current results of clinical outcomes in large populations.