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Dae Seog Heo
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MA11 - Biomarkers of IO Response (ID 912)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Immunooncology
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 10:30 - 12:00, Room 203 BD
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MA11.07 - Expression of LAG-3 and NY-ESO-1 In Tumor Cells is Promising Biomarker Predicting Durable Clinical Benefit of PD-1 Blockade in Advanced NSCLC (ID 12403)
11:10 - 11:15 | Author(s): Dae Seog Heo
- Abstract
- Presentation
Background
Anti-PD-1 antibodies are currently used in treating advanced non-small cell lung cancer (NSCLC). PD-L1 expression in tumor cell or immune cell is the only available predictive biomarker in the clinic. Lymphocyte activation gene-3 (LAG-3) is an inhibitory checkpoint in immune cells and NY-ESO-1 is an antigen expressed in tumor cells. We investigated LAG-3 and NY-ESO-1 protein expression and its relationship to response to anti-PD-1 therapy in NSCLC.
a9ded1e5ce5d75814730bb4caaf49419 Method
We retrospectively reviewed the medical records of 38 patients with advanced NSCLC who were enrolled in prospective clinical trials of nivolumab or pembrolizumab monotherapy (NCT01295827, NCT01905657, and NCT02175017) between October 2013 and April 2016 at Seoul National University Hospital and Seoul National University Bundang Hospital. Immunohistochemial staining (IHC) of NY-ESO-1(E978, Invitrogen), and PD-L1 (22C3, Dako) in tumor cell and LAG-3(EPR4392, Abcam) in immune cell was performed to determine protein expression.
4c3880bb027f159e801041b1021e88e8 Result
LAG-3 and NY-ESO-1 protein expression were assessed in 38 patients. LAG-3, NY-ESO-1 and PD-L1 were expressed in 76.3% (29/38), 50% (19/38) and 18.5% (7/36, 50% cut-off value), respectively. Sixteen patients with durable clinical benefit (DCB, anti-PD-1 therapy more than 6-month) were grouped as responder. NY-ESO-1 expression (DCB 11/19 vs 5/19, p= .05) and LAG-3 expression (DCB 16/29 vs 0/9, p= .003) were significantly correlated with the DCB to Anti-PD-1 therapy, while PD-L1 expression was identified in 5 patients with DCB (5/7 vs 11/29, p= .12). Patients with both NY-ESO-1 and LAG-3 expression had high rate of DCB (73.3%, 11/15 pts). With the results of the interaction with DCB, the calculation of positive predictive value and negative predictive value about durable clinical benefit is assessed and the significance of each measurement was proven by Fisher’s exact test. As a result, NPV of LAG-3 expression in tumor cell was 100% and PPV of each protein expression was LAG-3 (55.17%), NY-ESO-1(57.89%) and PD-L1 (71.43%) respectively. In survival analysis, LAG-3 expression was a significant predictor for PFS (HR 0.170; CI 0.066-0.437; p< .0001) and OS (HR 0.250; CI 0.140-0.599; p= .002).
8eea62084ca7e541d918e823422bd82e Conclusion
NY-ESO-1 expression on tumor tissue and LAG-3 expression on tumor microenvironment may be useful for identifying advanced NSCLC patients for the treatment of anti-PD-1 therapy. These protein markers seem quite promising and warrant further investigation in large sample size.
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OA11 - Thymic and Other Thoracic Tumours: Targeted Therapies, Biomarkers and Neo/Adjuvant Radiotherapy (ID 919)
- Event: WCLC 2018
- Type: Oral Abstract Session
- Track: Thymoma/Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 13:30 - 15:00, Room 205 BD
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OA11.05 - Phase II Study of Sunitinib in Patients with Thymic Carcinoma Previously Treated with Platinum-Based Chemotherapy (KOSMIC Trial) (ID 13228)
14:15 - 14:25 | Author(s): Dae Seog Heo
- Abstract
- Presentation
Background
Only one prospective study in western population suggests sunitinib is an effective treatment for thymic carcinoma (TC). We evaluated the clinical efficacy and toxicity of sunitinib in Korean patients with metastatic TC after platinum-based chemotherapy.
a9ded1e5ce5d75814730bb4caaf49419 Method
Between Sep 2015 and May 2017, we enrolled 25 patients with histologically confirmed platinum-refractory TC at three academic hospitals in Korea. Patients were eligible if they had progressive disease after one or more cytotoxic chemotherapy including platinum-based regimen, at least one measurable disease by RECIST (v1.1) and adequate organ function. Patients received 50mg of sunitinib on an alternative schedule (2weeks of treatment followed by 1 week without treatment) until objective progression of disease or unacceptable toxicity of treatment. The primary endpoint was objective response rate and tissue and blood specimen were collected for NGS panel analysis (170 genes, Hybrid capture based method). This trial was registered with Clinicaltrials.gov, number NCT 02623127.
4c3880bb027f159e801041b1021e88e8 Result
A total of 25 patients were enrolled in this trial. Median age was 62 (39-75) and 19 (76%) patients were male. Most patients (20 patients, 80%) received sunitinib as 2nd line treatment. Two patients discontinued treatment earlier than first tumor assessment due to toxicity and excluded from efficacy analysis. Among 23 evaluable patients, 5 (21.7%) patients had partial response and 16 (69.6%) patients achieved stable disease. Disease control rate (PR+SD>6m) was 56.5%. Median progression-free survival (PFS) was 15.2 months and 6 patients had ongoing responses at the time of analysis. Most common treatment-related adverse events were mucositis (12 patients, 48%), fatigue (9 patients, 36%), and hand-foot syndrome (9 patients, 36%). The most common grade 3/4 toxicity was thrombocytopenia (4 patients, 16%). Seventeen (68%) patients needed at least one dose reduction due to adverse events. Genomic profiling with NGS cancer panel revealed 2 patients with pathogenic KIT mutation (c.1879+1G>A and c.1671 G>C) who had PFS of 21.3m and 9.3m, respectively. In 15 patients with tumor tissue gene panel results, high tumor mutation burden (TMB) was significantly associated with longer PFS (median PFS not reached in TMB ≥30/MB vs. 3.45m in TMB <30/MB, P=0.03).
8eea62084ca7e541d918e823422bd82e Conclusion
Sunitinib with 2/1 schedule is an active treatment for TC after platinum-based chemotherapy.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
