Virtual Library
Start Your Search
L. Zhang
Author of
-
+
Best abstracts selected from submissions 5 (ID 6)
- Event: ACLC 2018
- Type: Oral Session
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 11/09/2018, 16:20 - 17:00, Crystal Ballroom 1
-
+
OA10 - CheckMate 078: Patient-Reported Outcomes (PROs) With Nivolumab vs Docetaxel in Advanced Non-Small Cell Lung Cancer (NSCLC) (ID 150)
16:20 - 17:00 | Author(s): L. Zhang
- Abstract
Background:
Nivolumab is approved in China for treatment of previously treated advanced NSCLC without EGFR/ALK alterations based on the findings of CheckMate 078 (NCT02613507), a randomized, open-label phase 3 study in a predominantly Chinese population that demonstrated superior overall survival with nivolumab versus docetaxel. Patients were randomized 2:1 to receive nivolumab 3 mg/kg Q2W or docetaxel 75 mg/m2 Q3W until disease progression or unacceptable toxicity. The results mirrored previous findings in the similar CheckMate 017/057 studies, which included few Asian patients. PROs in CheckMate 017/057 showed reductions in disease-related symptom burden and improvement in health-related quality of life (HRQOL). This study investigated whether similar improvements occurred in CheckMate 078.
Method:
Symptom burden was assessed using the Lung Cancer Symptom Scale (LCSS) average symptom burden index (ASBI). HRQOL was assessed using the LCSS 3-item global index (3-IGI) and EQ-5D-3L utility index (UI) and visual analog scale (VAS). Assessments for nivolumab and docetaxel occurred at baseline and every 4 and 3 weeks, respectively, up to week 24, and thereafter every 6 weeks for both treatments.
Results:
Of 504 randomized patients, 458 (91%) had evaluable PROs with baseline assessment and ?1 post-baseline assessment (90.4% were Asian and 60.0% had non-squamous tumor histology). Compliance was ?83% for all on-treatment PRO assessments. Ten or more patients remained on nivolumab and docetaxel until week 72 and 30, respectively. Time to first deterioration (TTD) was significantly prolonged with nivolumab vs docetaxel for all PRO measures; hazard ratios (95% confidence interval) were 0.47 (0.35?0.64) for LCSS-ASBI, 0.62 (0.47?0.83) for LCSS-3-IGI, and 0.56 (0.44?0.71) for both EQ-5D-3L VAS and UI. Deterioration rates at week 12 were significantly lower with nivolumab (LCSS, n=313; EQ-5D-3L, n=312) than docetaxel (LCSS, n=137; EQ-5D-3L, n=142) for LCSS-ASBI (31.6% vs 46.7%), EQ-5D-3L VAS (46.8% vs 58.5%), and EQ-5D-3L UI (36.5% vs 51.4%). Patients treated with nivolumab demonstrated clinically meaningful improvements for most LCSS-ASBI assessments after week 30 and all LCSS-3-IGI assessments after week 16; no clinically meaningful improvements were observed with docetaxel (descriptive). HRQOL improvements with nivolumab were observed with the EQ-5D-3L UI (weeks 20?72) and VAS (weeks 16?54), but most were not clinically meaningful.
Conclusion:
HRQOL and symptom burden improved with nivolumab vs docetaxel in CheckMate 078. Deterioration rates up to week 12 decreased and TTD was delayed with nivolumab vs docetaxel. Patients treated with nivolumab showed clinically meaningful improvement in symptom burden from baseline. These findings are consistent with those from CheckMate 017/057.
-
+
Poster Session (ID 8)
- Event: ACLC 2018
- Type: Poster Session
- Track:
- Presentations: 4
- Moderators:
- Coordinates: 11/07/2018, 00:00 - 00:00, Poster Hall
-
+
P026 - Impact of Prior Cancer History on the Overall Survival of Younger Patients with Lung Cancer (ID 202)
00:00 - 00:00 | Author(s): L. Zhang
- Abstract
Background:
Patients with a history of prior cancer are frequently excluded from cancer trials. Previous studies indicated that prior cancer does not adversely impact clinical outcomes for lung cancer patients older than 65 years. However, whether these research results are applicable to lung cancer patients aged younger than 65 years old remains unknown.
Method:
We identified younger lung cancer patients (<65 years) diagnosed between 2004 and 2009 in the SEER database. Propensity score matching were performed to balance differences in baseline characteristics between groups. Kaplan-Meier method and Cox proportional hazards model were used to evaluate the impact of prior cancer on overall survival (OS).
Results:
Among 103,370 eligible lung cancer patients, 15.18% (15696) had a history of prior cancer. Lung (25.83%), breast (14.13%), and prostate (8.85%) were the most common prior cancer. Localized and regional stages were accounting for 61.56% of prior cancers. More than 67.98% of prior cancer were diagnosed within 5 years. The median times of diagnosis for prior cancers were 38 months. The Kaplan-Meier curve (Figure 1 A) show an adverse effect of prior cancer on OS, compared to patients without an prior cancer (p=0.029). In COX regression analysis, patients with prior cancer had the similar OS as that of patients without a prior cancer (hazard ratio = 1.01, 95% confidence interval= 0.99 to 1.04, p=0.324). Subgroup analyses stratified by timing of prior cancer displayed almost the same tendency (p>0.05) (Figure 1 B). Early stage patients with prior cancer had adverse survival curves (p<0.05). Advanced stage patients with prior cancer had non-inferior survival (p>0.05).
Conclusion:
Prior cancer does not convey an adverse effect on clinical outcomes among advanced lung cancer patients age ? 65 years , regardless of timing of prior cancer. Broader inclusion trial criteria could be adopted in younger advanced lung cancer patients with a history of prior cancer. -
+
P038 - Docosapentaenoic Acid and Lung Cancer Risk: A Mendelian Randomisation Study (ID 54)
00:00 - 00:00 | Author(s): L. Zhang
- Abstract
Background:
Docosahexaenoic acid and eicosapentaenoic acid have been reported to be associated with lung cancer risk; however, it remains unknown whether docosapentaenoic acid (DPA), another kind of n-3 PUFA, is related to lung cancer risk. The aim of this study is to investigate the causal effect of DPA on lung cancer with Mendelian randomization (MR) method.
Method:
With a two-sample MR approach, we analyzed the summary data from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE, 8,866 individuals of European ancestry) Consortium and International Lung Cancer Consortium (ILCCO, 11348 lung cancer cases and 15861 controls; European ancestry). Three single nucleotide polymorphisms (SNPs) that were genome-wide significant (p<5*10-8; linkage disequilibrium r2 < 0.1) for plasma DPA levels in CHARGE were explored for their associations with lung cancer risk in the ILCCO. Analysis for two different histologic subtypes of lung cancer (adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC)) was performed to investigate whether the effect of DPA is associated with the histology of lung cancer. To investigate whether lung cancer might be a causal factor for DPA, we performed an MR analysis in the opposite direction using 3 SNPs linked to lung cancer. Evidence of directional pleiotropy averaged across all variants was sought using MR -
+
P101 - Intratumor Heterogeneity Comparison Among Different Subtypes of (ID 206)
00:00 - 00:00 | Author(s): L. Zhang
- Abstract
Background:
Intratumor heterogeneity (ITH) can lead to therapeutic failure, drug resistance, and poor survival. Understanding of ITH among different non-small cell lung cancer (NSCLC) subtypes is necessary. Circulating tumor DNA (ctDNA) released by tumor cell into the blood, can originate from any subclonal population within the tumor and therefore has great potential for presenting ITH. Whether ctDNA profile could represent these ITH is still an open question.
Method:
We performed 181 multi-region tumor tissues sequencing and matched ctDNA sequencing from 32 operative NSCLC to compare ITH among different NSCLC subtypes, including EGFR-mutant lung adenocarcinoma (LUAD), KRAS-mutant LUAD, EGFR&KRAS-wild-type LUAD, and lung squamous cell carcinoma (LUSC), and examine potential value of ctDNA for ITH analysis. If the somatic genetic alteration is shared by all the tissue regions, it is defined as trunk mutation. Otherwise, it is called branch mutation. ITH is evaluated by ITH index (ITHi). The ITHi will be higher, if the tumor has less trunk mutations.
Results:
EGFR-mutant LUAD showed significantly higher ITHi than KRAS-mutant LUAD/wild-type LUAD (P=0.03) and numerically higher ITH than LUSC. For trunk mutations, driver mutations were identified at a higher proportion than passenger mutations (60% vs. 40%, P=0.0023) in overall, especially in EGFR-mutant LUAD (86% vs. 14%, P=0.0004), while it was opposite in KRAS-mutant LUAD (40% vs. 60% , P=0.18). For branch mutations, the proportions of driver mutations and passenger mutations were similar for each NSCLC subtype. Additionally, for driver mutations, the proportions of oncogenes and tumor suppressor genes (TSGs) seemed to be similar both in the trunk (58% and 42%) and branch (49% and 51%) in general. However, oncogenes showed a higher proportion in EGFR-mutant LUAD, while TSG alterations had a strong enrichment in LUSC in trunk. ctDNA analysis showed unsatisfactory detections of tumor-derived trunk and branch mutations (43% vs. 23%;, P=4.53e-6) among all NSCLC subtypes. LUSC and EGFR&KRAS-wild-type LUAD had higher proportions for tumor-derived trunk mutations (81% and 53%) than those in EGFR-mutant LUAD (30%) and KRAS-mutant LUAD (22%), while the detections for tumor-derived branch mutations in ctDNA were extremely poor (from 13% to 25%) among all above NSCLC subtypes.
Conclusion:
EGFR-mutant LUAD has the highest ITHi than other NSCLC subtypes, offering further understanding of tumorigenesis mechanisms among different NSCLC subtypes. Besides, ctDNA analysis shows unsatisfactory detections of tumor-derived mutations among all NSCLC subtypes, thus it maybe not an appropriate method to reflect ITH. -
+
P102 - The Correlations of Tumor Mutational Burden Among Single-region Tissue, Multi-region Tissues And Blood in NSCLC (ID 208)
00:00 - 00:00 | Author(s): L. Zhang
- Abstract
Background:
Tumor mutational burden (TMB) is emerging as a practical biomarker for response to immune checkpoint inhibitors (ICIs). Non-small cell lung cancer (NSCLC) patients with high-level tissue TMB (tTMB) or blood TMB (bTMB) are associated with better efficacy of ICIs. However, the correlations of single-region tTMB, multi-region tTMB and bTMB remain to be determined. Moreover, whether intratumor heterogeneity (ITH) has impact on TMB should be clarified.
Method:
We collected multi-region tumor tissues with matched blood from 32 operative NSCLC and explored the correlations among one-region tTMB, multi-region tTMB and bTMB through a 1021-gene panel sequencing. One-region tTMB was defined as the number of somatic non-synonymous mutations from single region. multi-region tTMB was calculated with non-repetitive mutations from all regions. bTMB was analyzed with tumor-derived mutations from ctDNA. TMB of >9 mutations/Mb was classified as high, using the top quartile threshold of 2000 samples from database of Geneplus. Besides, we used TMB fold-change, computed by the mean tTMB of single, double, and triple regions through a random iterated algorithm, to evaluate the influence of the enrolled region numbers on tTMB and explored the impact of ITH on tTMB.
Results:
Both of single-region tTMB and bTMB showed strong correlations with multi-region tTMB, while the former correlated better (Pearson r=0.94, P=2E-84, Pearson r=0.47, P=0.0067). It showed extremely high specificity (100%) but relatively low sensitivity (43%) when using bTMB define TMB-high patients, while most false-negative predictions were in early-stage patients. The classification accuracy was higher in late-stage patients (83%) than in early-stage patients (70%).Compared to single region, we found significantly enhanced tTMB fold-change if taking multi-regions for consideration. However, it showed insignificant tTMB fold-change increase if the included regions' number more than three. Moreover, the tTMB fold-change increased more sharply in ITH-high group compared with the ITH-low group significantly (fold-change 2.32 vs. 1.02, P=8.879e-05). The conversion rate of tTMB level status (conversion of tTMB-low to tTMB-high) in the ITH-high group was numerically higher than that in the ITH-low group (16.67% vs. 3.84%).
Conclusion:
Single-region tTMB has stronger correlation with multi-region tTMB compared with bTMB, revealing the limitation of TMB analysis using ctDNA. ITH has an impact on tTMB, especially in high-level ITH patients, thus firstly demonstrating tTMB heterogeneity and providing an explanation for why some low-TMB patients evaluated by a single region biopsy still achieve benefit from ICIs.
