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Yanyan Lou
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-113 - Phase 1b Trial of Cabozantinib or Cabozantinib Plus Atezolizumab in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) (ID 1455)
09:45 - 18:00 | Author(s): Yanyan Lou
- Abstract
Background
Cabozantinib is an inhibitor of tyrosine kinases involved in tumor growth, angiogenesis, and immune regulation, including MET, VEGFR, RET, ROS1, and TAM family kinases (Tyro3, AXL, MER). Preclinical and clinical studies suggest that cabozantinib promotes an immune-permissive tumor environment, which may enhance response to immune checkpoint inhibitors (ICIs) such as the anti–PD-L1 mAb atezolizumab. Cabozantinib has demonstrated clinical activity in phase 1/2 studies of advanced NSCLC. Atezolizumab is approved for select patients with advanced NSCLC as monotherapy or as part of a combination regimen. Clinical studies in solid tumors, including NSCLC, indicate that the combination of a VEGF-targeting agent with an ICI may reverse ICI resistance.Here we present the study design of an ongoing phase 1b trial of cabozantinib alone or in combination with atezolizumab that includes cohorts with advanced non-squamous (nsq) NSCLC.
Method
This global, phase 1b, open-label trial (COSMIC-021) is evaluating the safety, tolerability, preliminary efficacy, and pharmacokinetics of cabozantinib alone or in combination with atezolizumab (NCT03170960). The study consists of a dose-escalation stage (completed) and an expansion stage. In the expansion stage, 18 cohorts are being enrolled at the recommended expansion dose of cabozantinib (40 mg po qd) + a standard dose of atezolizumab (1200 mg q3w IV), including 3 advanced NSCLC cohorts: (1) nsqNSCLC with prior ICI therapy, (2) nsqNSCLC without prior systemic anticancer therapy for metastatic disease, and (3) EGFR-mutant nsqNSCLC with prior EGFR-targeting therapy. Thirty patients are being enrolled per cohort, with potential for extended enrollment pending Study Oversight Committee review. Two exploratory single-agent cohorts (N=30) are being enrolled to receive a 60-mg dose of cabozantinib, including a cohort of patients with nsqNSCLC who received prior ICI therapy. Patients will continue treatment as long as they experience clinical benefit per investigator or until unacceptable toxicity. The primary endpoint of the expansion stage is the objective response rate for each cohort. Exploratory objectives include correlation of tumor and plasma biomarkers and immune cell profiles with clinical outcome.
Result
Section not applicable
Conclusion
Section not applicable
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P1.12 - Small Cell Lung Cancer/NET (ID 179)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.12-08 - The Impact of Patient Age and Socioeconomic Factors on Clinical Outcomes in Small Cell Lung Cancer (SCLC): A National Study (Now Available) (ID 1447)
09:45 - 18:00 | Author(s): Yanyan Lou
- Abstract
Background
SCLC represents one of the most aggressive cancers with limited treatment options. Chemotherapy with or without radiation therapy remain the backbone treatment for this challenging disease. The impact of age and other socioeconomic factors on treatment modalities and clinical outcomes remain largely unknown. This study investigates the demographic, clinical, socioeconomic, and treatment modalities in each age group and the impact of patients’ age on survival.
Method
The National Cancer Database with NSCLC incident cases between 2004-2014 was used. Clinical factors including Charlson‐Deyo comorbidity score, TNM staging, tumor histology, and type of treatment, demographic features, socioeconomic status and overall survival (OS) were analyzed by age of diagnosis, accounting for multivariate factors in NCDB.
Result
A total of 214,096 SCLC patients were included in the analysis. Median age at diagnosis was 67 years old (y/o). OS including all stages is 10.97 months for <60 y/o; 9.43 months for 60-69 y/o; 7.20 months for 70-79 y/o and 3.42 months for ≥ 80 y/o respectively (p<0.0001). The impact of age on survival is more prominent in stage I, II and III patients than those in stage IV patients. Patients ≥ 80 y/o are associated with significant smaller tumor size (41 mm vs 50 mm, p<0.0001) and more stage I cancer at diagnosis (3.8% vs 6.9%, p<0.0001) compared to patients <60 y/o respectively. Patients ≥ 80 y/o are associated with high income, high education and Pacific geographic region. Hispanics, Asians, females, and patients younger than 60 y/o are independently associated with improved OS. Despite comparable comorbidity, patients with ≥ 80 y/o are treated differently and received much less aggressive therapy including radiation therapy and/or chemotherapy at each stage (p<0.0001).
Conclusion
The overall survival of SCLC is significantly impacted by patient’s age and socioeconomic factors. In particular, elderly patients are associated with significantly smaller tumor size, more stage I at diagnosis, however, they are under-treated and have worse survival compared to younger patients.
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P2.17 - Treatment of Early Stage/Localized Disease (ID 189)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.17-14 - Impaired Immune Defense in Tumor Micro-Environment Is Associated with Risk of Recurrence in Early Stage Lung Adenocarcinoma (ID 1977)
10:15 - 18:15 | Presenting Author(s): Yanyan Lou
- Abstract
Background
Despite curative surgery with or without chemotherapy, 27-76% of surgically resected early stage lung cancer will unfortunately develop recurrence which is often fatal. Platinum-based adjuvant chemotherapy in NSCLC improves cure rates in only 5% of patients at the cost of significant toxicities. Developing biomarkers to select high risk patients and strategies to reduce recurrence in early stage lung cancer are critical.
Method
Thirty surgically resected primary lung adenocarcinomas from 16 patients with lung cancer recurrence and 14 patients without recurrence in 4 years were included in this study. Among these 30 patients, 27 have either stage I or II. RNA sequencing (694 genes and 14 key immuno-oncology (IO) pathways) was determined using nanoString technology and RNA from primary tumors from recurrent versus non-recurrent patients.
Result
Chemokines including CCL18, CCL23, CXCL1, CXCL2, CCL26 and chemokine receptors CXCR2, CX3CR1 and TNFRSF10C were significantly decreased in tumors from patients who had recurrence versus those from patients without recurrence. By contrast, genes related to cancer associated fibroblasts in the stromal microenvironment such as LRRC15 and genes involved in release of cancer cell antigens were significantly increased in adenocarcinomas from recurrent patients.
Conclusion
Our results suggest that recurrence in early stage lung adenocarcinoma might be related to impaired immune defense such as decreased immune cell trafficking and antigen release in tumor micro-environment. Further study with larger sample size is warranted.
