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J. Su
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P1.07 - Immunology and Immunotherapy (ID 693)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.07-042 - PD-L1 and CD8 Expression in EGFR-Mutant or ALK-Rearranged Patients with Lung Cancer (ID 10407)
09:30 - 09:30 | Author(s): J. Su
- Abstract
Background:
Several studies indicate no response to check-point inhibitors on non-small-cell lung cancer with either EGFR-mutant or ALK-rearranged patients,of whom majority of international clinical trials involving PD-1/L1 inhibitors excluded. No solid evidences to interpret the underlying mechanism of poor clinical benefit to patients through PD-1/L1 inhibitors with driver genes mutation.
Method:
From 2010 to 2016, 482 patients and 263 patients with clinically operable lung cancer and advanced lung cancer respectively were collected at Guangdong Lung Cancer Institute (GLCI). All patients have detected for EGFR as well as ALK status. CD8 and PD-L1 expression was scored by immunohistochemistry with SP142 antibody. Five years survival rate was also analyzed.
Result:
Patients were assigned to EGFR/ALK positive group (344 cases) or negative group (401 cases). EGFR/ALK positive group contains 5.52% PD-L1+/CD8+; 11.92% PD-L1-/CD8+; 18.90% PD-L1+/CD8- and 63.66% PD-L1-/CD8-. EGFR&ALK negative group contains 13.97% PD-L1+/CD8+; 6.98% PD-L1-/CD8+; 30.42% PD-L1+/CD8- and 48.63% PD-L1-/CD8-. In EGFR/ALK positive group, PD-L1+/CD8+ is lower but PD-L1-/CD8- is higher than that of EGFR&ALK negative group (P<0.001). Significant statistical differences of 5 years survival rate were observed between four subgroups in EGFR/ALK positive group (PD-L1+/CD8+:41.9%, PD-L1-/CD8+: 91.0%, PD-L1+/CD8-: 75.4%, PD-L1-/CD8-: 69.7%; P=0.003). And there were no survival differences in EGFR&ALK negative group((PD-L1+/CD8+: 66.5%, PD-L1-/CD8+: 76.9%, PD-L1+/CD8-: 62.3%, PD-L1-/CD8-: 70.6%; P=0.341).
Conclusion:
Immunotherapy with PD-1/L1 inhibitors may not be suitable for EGFR-mutant or ALK-rearranged lung cancer patients with little co-expression of PD-L1 and CD8. However, these patients with such diver genes mutation reveal the best survival in PD-L1-/CD8+ subgroup and the worst survival in PD-L1+/CD8+ subgroup. Figure 1
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P2.03 - Chemotherapy/Targeted Therapy (ID 704)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.03-054 - EGFR Mutation with Acquired C-MET Positive Reveals Potential Immunotherapeutic Vulnerabilities (ID 10436)
09:30 - 09:30 | Author(s): J. Su
- Abstract
Background:
There are few effective strategies for C-MET positive advance non-small-cell lung cancer(NSCLC) patients with epidermal growth factor receptor(EGFR) inhibitor resistance.The efficacy of PD-1 blockade immunotherapy and even the status of PD-L1 expression in such population is unclear.
Method:
Patients diagnosed as advanced NSCLC synchronously tested for EGFR status, expression of PD-L1 and C-MET at the Guangdong Lung Cancer Institute (GLCI) from 2015 to 2017 were collected.PD-L1 expression on tumor cells and immune cell was evaluated using a three-tiered grading system. C-MET positive was define as immunohistochemistry staining (2+/3+) in ≥ 50% of tumor cells. A chi-squared test was used to assess the relationships between C-MET positive and PD-L1 expression.
Result:
A total of 487 eligible cases were selected including 166 EGFR mutant and 321 wild type patients.In the general population(n=487),the difference of PD-L1 expression were observed between C-MET positive group and C-MET negative group (65.3% vs 31.7%, P=0.001),which was in accordance with the result from the Cancer Genome Atlas (TCGA) dataset (n=512,P<0.001).Furthermore,among the EGFR mutant patients (n=166), PD-L1 expression was showed in 58.1% of C-MET positive group and 28.5% of C-MET negative group,P value <0.001. Subsequently,T790M negative was identified in 55%(47/86) of EGFR TKI resistant patients (n=86).In this subgroup,a significant increase of PD-L1 expression was demonstrated in C-MET positive group compared to C-MET negative group(66.7% vs 34.6%,P=0.027).Finally, clinical efficacy of immunotherapy was further confirmed in 2 C-MET positive advanced lung adenocarcinoma patients with remarkable response to PD-1 blockade immunotherapy who had disease progression after C-MET inhibitors.Figure 1
Conclusion:
C-MET positive maybe associated with high PD-L1 expression in advanced NSCLC providing therapeutic insight into targeting the PD-1/PD-L1 pathway in EGFR inhibitor-resistant NSCLC with C-MET positive and T790M negative.
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-051 - Dramatic Response to Afatinib in EGFR-Mutant Lung Adenocarcinomas After Resistance to First-Generation EGFR Inhibitors: A Brief Report (ID 9706)
09:30 - 09:30 | Author(s): J. Su
- Abstract
Background:
T790M inhibitor, a third-generation epithelial growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), was significantly superior to chemotherapy for EGFR-mutant patients with advanced non-small-cell lung cancer (NSCLC) harboring T790M mutation after resistance to the first-generation EGFR-TKIs. However, for those without acquired T790M mutations or MET amplification, few data showed whether the second-generation EGFR-TKI could overcome resistance to the first-generation EGFR-TKIs.
Method:
EGFR mutation was detected by amplification refractory mutation system (ARMS) technology. Overexpression of MET was determined by immunohistochemistry (IHC), and MET amplification was detected by FISH. Next generation sequencing (NGS) was used to test tumor tissues before and after resistance to TKIs.
Result:
Patient 1 was a 53-year-old Asian male, who underwent surgery followed by adjuvant chemoradiotherapy with an 11 months of disease-free survival. A biopsy was performed and revealed an activating deletion mutation in exon 19 of the EGFR. He started gefitinib 250mg once daily and achieved an initially good partial response (PR) followed by continuously stable disease for a progression-free-survival (PFS) about 29 months. A rebiopsy showed that exon 19 deletion mutation still existed without an acquired T790M mutation or MET amplification. He refused to receive chemotherapy so we prescribed afatinib 40mg daily. He then achieved a dramatic PR 23 days later which was confirmed 1.5 months after that. We sent tumor tissue of the patient before and after TKI therapy for NGS, the result showed a decreasing abundance of EGFR exon 19 deletion without T790M mutation, MET amplification and Her2 mutation/amplification. Patient 2 was a 63-year-old Asian female harboring EGFR exon 20 insertion (A763-Y764 ins), who received first and second lines of chemotherapy with short PFSs. He was enrolled in the trial of allitinib (AST-1306) as the third line therapy with the best response of stable disease(SD) and the PFS of 7 months. A later rebiopsy showed the strong overexpression of MET, but the forth-line therapy crizotinib failed. He then received chemotherapy as the-fifth line therapy, 4 cycles later he progressed. So he started afatinib 40mg daily. His symptoms were relieved significantly 5 days later, and PR was confirmed 1.5 months later.
Conclusion:
Afatinib might overcome resistance to the first-generation EGFR-TKIs for EGFR-mutant patients with advanced NSCLC without acquired T790M mutation or MET amplification. Further investigations are warranted.
