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Ziping Wang
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P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.01-62 - The Third Generation Irreversible EGFR Inhibitor HS-10296 in Advanced Non-Small Cell Lung Cancer Patients (ID 13138)
16:45 - 18:00 | Author(s): Ziping Wang
- Abstract
Background
The epidermal growth factor receptor (EGFR) T790M mutation is the most common mechanism of drug resistance to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) patients with sensitizing EGFR mutations. The third generation irreversible EGFR inhibitor HS-10296 has been shown to be safe and effective against both EGFR TKI-sensitizing and T790M resistance mutations in preclinical studies.
a9ded1e5ce5d75814730bb4caaf49419 Method
A Phase I, open-label, multi-center clinical trial was conducted in patients with locally advanced or distant metastatic NSCLC who have progressed following prior therapy with EGFR TKIs. The study was consisted of dose-escalation cohorts (55, 110, 220 and 260 mg) and dose-expansion cohorts (55, 110 and 220 mg) with once daily oral administration of HS-10296. In each expansion cohort, tumor biopsies were collected for central determination of EGFR T790M status. Patients were assessed for safety, tolerability, pharmacokinetics and efficacy of HS-10296.
4c3880bb027f159e801041b1021e88e8 Result
A total of 117 patients (median age 60) received at least one dose of HS-10296 across multiple sites in China (43 patients), Taiwan (69 patients) and the United States (5 patients). Maximum tolerated dose（MTD）has not been reached in this study. The most common adverse events were grade1/2 rash, pyrexia, upper respiratory tract infection, constipation, diarrhoea and blood creatine phosphokinase elevation. Drug-related serious adverse events were anemia (0.8%), blood creatinine elevation (0.8%), anemiarhabdomyolysis (0.8%) and blood creatine phosphokinase elevation (0.8%) occurred mainly in the cohorts with higher doses at 220 mg or 260 mg, respectively. These data demonstrated favorable tolerability and safety of HS-10296 in patients enrolled. The pharmacokinetics of HS-10296 was dose proportional and the plasma half-life was 30.7~37.5 hours. Among 82 evaluable patients (18 in escalation cohorts and 64 in expansion cohorts) with the EGFR T790M mutation, the overall objective response rate (ORR) was 52.4% (43/82; 95% CI, 41.6 to 63.3), while disease control rate (DCR) was 91.5% (75/82; 95% CI, 85.4 to 97.5). 110mg cohort showed better DCR (97.2% VS. 86.1%) than 55mg cohort. Phase II study is ongoing with the dose at 110 mg.
8eea62084ca7e541d918e823422bd82e Conclusion
HS-10296 has the potential to provide clinical benefit to locally advanced or distant metastatic NSCLC patients with EGFR T790M mutation who had disease progression following prior therapy with EGFR TKIs.
(The study was sponsored by Jiangsu Hansoh Pharmaceutical Co., Ltd.; ClinicalTrials.gov number, NCT02981108)
6f8b794f3246b0c1e1780bb4d4d5dc53
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P1.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 948)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.16-62 - A Nomogram to Predict Disease-Free Survival After Curative Resection of Non-Small Cell Lung Cancer (ID 11913)
16:45 - 18:00 | Presenting Author(s): Ziping Wang
- Abstract
Background
The aim of this study was to find clinicopathologic variables associated with disease-free survival (DSF) and develop a prognostic nomogram for patients with curative resected non-small-cell lung cancer (NSCLC) and compare the value of the nomogram to the seventh AJCC TNM classification.
a9ded1e5ce5d75814730bb4caaf49419 Method
A nomogram to predict DFS following surgical resection of NSCLC was constructed using a single-institutional cohort of 805 patients who underwent curative resection of lung adenocarcinoma in the Cancer Hospital of the Chinese Academy of Medical Sciences (Beijing, China) between January 2003 and December 2013. For nomogram construction and validation, we randomly assigned two thirds of the patients to the training cohort (n=605) and one third to the validation cohort (n=260). The median age of training cohort was 57 years (range, 25-76) and the proportion of male and female patients was 64.8% vs. 35.2%. Half of the patients (49.8%) presented with early-stage disease and 85.3% patients received adjuvant chemotherapy alone. The predictive discriminative and calibration were measured by concordance index (C-index), risk group stratification and calibration plot.
4c3880bb027f159e801041b1021e88e8 Result
The median disease-free survival for the total cohort was 23.2 months (95% CI, 21.3-26.4 months). The 1-, 3- and 5-year disease-free survival was 71.3%, 39.5% and 32.3%, respectively. The nomogram included 8 important variables based on a Cox proportional hazards regression modeling of the training cohort: histology, differentiation, nodal status, AJCC T category, primary tumor location, type of surgical resection, adjuvant radiotherapy and regimen. Each patient with a higher score had a worse prognosis. Prognostic discrimination was performed by dividing the predicted nomogram score into quartiles that were then used to plot Kaplan-Meier curves. The nomogram was able to stratify patients into 4 distinct incremental 3-year prognostic groups (quartile 1, 73.0%; quartile 2, 49.6%; quartile 3, 30.6%; and quartile 4, 9.3% [P <0.001]). Both in the training and validation cohort, the C-index of the nomogram for DFS prediction was superior to the TNM category prediction (training cohort, 0.694 vs. 0.640; P<0.01 and validation cohort, 0.662 vs. 0.602; P<0.01). The 200-sample bootstrapped calibration curves for probability of 3- and 5-year disease-free survival (PFS) showed optimal agreement between nomogram prediction and actual observation.
8eea62084ca7e541d918e823422bd82e Conclusion
This novel nomogram provides an individualized prediction of DFS in NSCLC patients after radical surgery and may assist the clinical treatment decision making and clinical trials designing.
6f8b794f3246b0c1e1780bb4d4d5dc53
