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JCSE01 - Joint IASLC-CSCO-CAALC Session (ID 63)
- Event: WCLC 2019
- Type: Joint IASLC-CSCO-CAALC Session
- Presentations: 1
- Moderators:Chunxue Bai, Tony Mok, Yi-Long Wu, Qing Zhou, Nan Wu
- Coordinates: 9/07/2019, 07:00 - 11:15, Toronto (1985)
JCSE01.22 - Tumor Microenvironment Is Associated with Efficacy of PD-1/PD-L1 Inhibitors in Patients with Primary Pulmonary Lymphoepithelioma-Like Cancer (ID 3436)
07:00 - 11:15 | Author(s): Kai Yin
Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is Epstein-Barr (EB) virus related subtype of non-small-cell lung cancer. Evidence of immunotherapy in LELC is scarce. The role of immune markers in tumor microenvironment and their relation with the efficacy of PD-1/PD-L1 inhibitors in LELC remain poorly explored.Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is Epstein-Barr (EB) virus related subtype of non-small-cell lung cancer. Evidence of immunotherapy in LELC is scarce. The role of immune markers in tumor microenvironment and their relation with the efficacy of PD-1/PD-L1 inhibitors in LELC remain poorly explored.
A total of seventeen patients treated with PD-1/PD-L1 inhibitors in Guangdong Lung Cancer Institute were enrolled. We detected multiple immune markers including PD-L1, IDO1, TIM3, LAG3, CD4 and CD8 by immunohistochemistry in eleven of these patients. Dynamic changes of the checkpoint biomarkers in two patients (#10 and #11) treated with PD-1 inhibitors were analyzed. Tumors with 1% TPS (tumor proportion staining) were defined as PD-L1 positive. H-score of PD-L1, IDO1, TIM3 and LAG3 was calculated by multiplying percentage of positively stained cells and intensity score (0, absent; 1, weak; 2, moderate; 3, strong). For CD4 and CD8, the H-score equals the percentage of staining positive lymphocytes among all nucleated cells.
In the 17 patients, most of them suffered from lines of chemotherapy (only two patients (2/17, 11.8%) received PD-1/PD-L1 inhibitors as the first line therapy). There are eight males and nine females. The median age was 47 years (range from 13 to 63). All of them were stage IIIB and IV. Thirteen of seventeen patients received single agent PD-1/PD-L1 inhibitor. PD-1/PD-L1 inhibitor showed an 82.4% disease control rate and 17.6% objective response rate. The median progression free survival was 7.4 months. The overall survival was not reached. Biomarkers of IDO1, LAG3, and TIM3 were not mutually exclusive with PD-L1, and could be highly expressed in responder patients to PD1/PD-L1 inhibitors. Notably, TIM3 expression was up-regulated at disease progression in two patients treated with PD-1 inhibitor.
PD-1/PD-L1 inhibitors had preliminary good activity, and TIM3 up-regulation might be a mechanism of resistance to PD-1 inhibitors in advanced pulmonary LELC.
P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
P1.01-28 - Mutational Heterogeneity Between Primary Pulmonary Cancer Lesions and Matched Brain Metastases (Now Available) (ID 3133)
09:45 - 18:00 | Author(s): Kai Yin
Brain metastasis (BM) is a severe and common lethal condition in non-small cell lung cancer patients. A few data have been reported about the molecular landscape of genomic alterations in BM of non-small cell lung cancer (NSCLC). Yet little is known about molecular heterogeneity and evolution process during the cancer metastases from lung to brain. We seek to profile the genomic alterations in paired specimens of primary lung lesions (PL) versus brain metastasis (BM).Method
Paired specimens of thirteen patients with BM were collected. MassARRAY LungCarta (26 genes) and Next Generation Sequencing (NGS, 285 genes) assays were performed to generate genomic profiles.Result
Thirteen patients were aged mean 58 (range 40-74), 10 adenocarcinoma and 2 squamous carcinoma and 1 small cell lung cancer, 9 males and 4 females, 5 smokers and 8 non-smokers, 7 stage IV, 3 stage III, 2 stage II and 1 stage I. By LungCarta test, we detected 6 EGFRm (1 concurrent STK11, 1 concurrent TP53), 2 KRASm, 1 STK11m cases and 4 wild type primary lung cancers. All corresponding BM lesions harbored the same mutations of EGFR, KRAS, TP53 and STK11, and additional EGFR T790M in 1 EGFR mutated case. By NGS test, in 9 patients all above mutations were detected along with additional genomic alterations. There were average mutated 9 genes in primary lung lesions and 13 mutated genes in BM. Common altered genes in PL included EGFR, KRAS, TP53, STK11, NF2, ARID1B and ATM. Shared mutated genes between PL and BM had EGFR, KRAS, TP53, KMT2C and etc. BM specific altered genes included ARID1A, SMARCA4, ATM, ATR, EPHA5, RB1, KMT2C, LRP1B, and SETD2, etc. Notably, genes involved in the chromatin remodeling or modification and cell cycle pathways were enriched in BM.Conclusion
There were heterogeneous molecular alterations between PL and BM of NSCLC. Differential genes involved in the chromatin remodeling and modification and cell cycle checkpoint may be highly related to the process of BM, suggesting future therapeutic development on these potential molecular targets.