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Baohui Han
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EP1.01 - Advanced NSCLC (ID 150)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.01-65 - The Relationship Between Preliminary Efficacy and Prognosis After First-Line EGFR-TKI Treatment of Advanced NSCLC (Now Available) (ID 711)
08:00 - 18:00 | Author(s): Baohui Han
- Abstract
Background
Nowadays, patients with EGFR-TKI-sensitive advanced non-small cell lung cancer (NSCLC) receive EGFR tyrosine kinase inhibitors (EGFR-TKIs) as first-line treatment. We aimed to analyze the relationship between preliminary efficacy (tumor shrinkage within 1 month) and progression-free survival (PFS) after first-line EGFR-TKI treatment.
Method
A total of 82 patients with EGFR-TKI-sensitive advanced NSCLC confirmed by histopathology from January 2013 to January 2017 were retrospectively analyzed. All patients received first-line EGFR-TKI treatment and follow-up at Shanghai Chest Hospital.
Result
Of 82 patients, 42 (51.2%) patients achieved partial response (PR) within 1 month, and 40 (48.8%) patients achieved stable disease (SD: -30%~0) within 1 month. The median PFS among all patients was 10 months. The median PFS in patients achieving PR within 1 month was 10 months. The median PFS in patients achieving SD (-30%~0) within 1 month was 9.3 months. There was no statistically significant difference between PR within 1 month and SD (-30%~0) within 1 month (P=0.620). In the EGFR-sensitive mutation subgroup, there was also no statistically significant difference between PR within 1 month and SD (-30%~0) within 1 month. Univariate and multivariate analysis of first-line EGFR-TKI treatment showed that age, EGFR mutation type, and T staging had effects on PFS. Patients who were more than 65 years old, had EGFR 19del mutation, along with a T staging less than 4, had a longer PFS; these differences were statistically significant. Liver metastasis, bone metastasis, and brain metastasis were not shown to be related to PFS.
Conclusion
For patients with EGFR-TKI-sensitive advanced NSCLC, there is no correlation between preliminary efficacy (tumor shrinkage within 1 month) and PFS after first-line EGFR-TKI treatment.
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EP1.03 - Biology (ID 193)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 3
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.03-11 - Mechanisms of Gefitinib Plus Pemetrexed on Human Non-Small Cell Lung Cancer (Now Available) (ID 1402)
08:00 - 18:00 | Author(s): Baohui Han
- Abstract
Background
Resistance to EGFR tyrosine kinase inhibitors (EGFR-TKI) is often acquired in non-small cell lung cancer (NSCLC) patients during treatment. We previously demonstrated that combined treatment with EGFR-TKI gefitinib plus chemotherapy improved progression-free survival (PFS) in NSCLC patients carrying sensitive EGFR mutations.
Method
Pharmacological interaction between gefitinib and pemetrexed was evaluated in NSCLC cell line PC-9 using MTT assay. The influence of combined treatment with gefitinib plus pemetrexed on gene expression profiles and signaling pathways has been investigated using microarray and Ingenuity Pathway Analysis (IPA).
Result
Synergistic inhibitory effect between gefitinib and pemetrexed was observed in NSCLC cell line PC-9. Figure 1A suggested representative proliferation inhibitory effects of gefitinib, pemetrexed and combined treatment for 48 hours. Figure 1B showed CI values of concurrent gefitinib-pemetrexed treatment in PC-9 NSCLC cell line. CI values at ED50, ED75 and ED90 were shown.
Furthermore, widespread gene expression changes and critical signaling pathways were induced significantly by combined treatment in PC-9 cells. Figure 2A was heatmap of gene expression prolifes in human NSCLC PC-9 cell line treated with gefitinib (blue), pemetrexed (purple) or gefitinib-pemetrexed combination (orange) with the criteria P<0.05 and ▏fold change ▏>1.5. Genes and samples were listed in rows and columns, respectively. A colour standard for data normalization was shown at the bottom with green representing downregulated genes while red representing upregulated genes. In Figure 2B, pathway enrichment of differential expressed genes was analysed using Ingenuity Pathway Analysis (IPA). Signaling pathways shown here were based on a P<0.0001. Figure 2C showed heatmap of critical pathways affected by combined treatment as compared to gefitinib single treatment. Heatmap colour represented the Z-score of signalling pathways. Z-score>0 meant the signalling pathway was stimulated by related treatment while Z-score<0 meant the signalling pathway was inhibited by related treatment.
Conclusion
Gene expression profiles revealed potential signaling pathways contributing to the synergism.
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EP1.03-12 - IL-10 Promotes Tumor Aggressiveness in Non-Small Cell Lung Cancer via Down-Regulated the Expression Level of miR-125b (Now Available) (ID 1776)
08:00 - 18:00 | Author(s): Baohui Han
- Abstract
Background
IL-10 is an anti-inflammatory factor with bi-directional regulation of tumor immunity. While, the role and mechanism of IL-10 in lung cancer is not clear. The aim of the present study was to identify the potential mechanisms of IL-10 in lung carcinogenesis.
Method
RT-PCR was used to detect the expression of miRNAs and mRNAs. CKK8 and flow cytometry assays was performed for the function experiments. Microarray analysis and IPA analysis were used to predict the potential signal pathway.
Result
IL-10 was found significantly associated with the risk of non-small cell lung cancer (NSCLC). Meanwhile, the expression level of miR-125b in NSCLC cell line was dramatically decreased when stimulated by IL-10. The results of cell function experiments showed that miR-125b inhibited the tumor promoting effects of IL-10 in NSCLC. Then, microarray and IPA analysis found that IGF-1 signaling pathway was significantly activated after down-regulated the expression of miR-125b.
Conclusion
IL-10 promotes tumor aggressiveness via down-regulated the expression level of miR-125b in lung cancer.
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EP1.03-22 - Prognostic Value of Serum Inflammation Biomarkers in Early Stage Lung Adenocarcinoma (Now Available) (ID 1753)
08:00 - 18:00 | Author(s): Baohui Han
- Abstract
Background
Non-small cell lung cancer is the main cause of cancer-related death worldwide, with a low 5-year survival rate even in early-stage. And adenocarcinoma accounts for the majority of all Non-small cell lung cancer cases. Biomarkers to identify prognosis of early stage lung cancer are needed. Increasing evidences indicate a relationship between inflammation and lung carcinogenesis. One of our previous studies found inflammation biomarkers, BLC and MDC, are significantly related with the risk of early stage lung cancer. The present study was performed to evaluated the value of inflammation biomarker in predicting the prognosis of early stage lung adenocarcinoma.
Method
Ten inflammation biomarkers were tested by Luminex bead-based assay in 157 patients with resected early-stage lung adenocarcinoma (IA-IIB) from whom serum samples were collected pre-surgery.
Result
A total of 152 early stage lung adenocarcinoma patients were analyzed in this study. The mean age (SD) of was 59.9 (9.4) years. 58.6% of them were females, and never smokers accounted for 84.0%. By TNM stage, 109 (71.7%) patients were at stage I and 43 (28.3%) at stage II. The median follow-up time was 60.6 months. Patients with higher MIG levels were at a 70% reduced risk of recurrence compared with patients with lower MIG levels (HR=0.3, 95% CI: 0.1–0.7, p=0.0035). As for BLC, patients with higher levels had the risk of recurrence decreased by 50% (HR=0.5, 95% CI: 0.3–0.9, p=0.031) compared with patients with lower levels. After the Bonferroni correction, only MIG was significantly associated with the recurrence risk of early stage lung adenocarcinoma. For overall survival (OS), patients with higher MIG levels were still have a reduced dead risk compared with the lower group (p=0.0065).
Conclusion
Our results demonstrate for the first time that pretreatment MIG level was identified as a protective factor for the prognosis of early stage lung adenocarcinoma.
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JCSE01 - Joint IASLC-CSCO-CAALC Session (ID 63)
- Event: WCLC 2019
- Type: Joint IASLC-CSCO-CAALC Session
- Track:
- Presentations: 1
- Now Available
- Moderators:Chunxue Bai, Tony Mok, Yi-Long Wu, Qing Zhou, Nan Wu
- Coordinates: 9/07/2019, 07:00 - 11:15, Toronto (1985)
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JCSE01.11 - Efficacy and Safety of Sintilimab with Anlotinib as First-Line Therapy for Advanced Non-Small Cell Lung Cancer (NSCLC) (Now Available) (ID 3425)
07:00 - 11:15 | Presenting Author(s): Baohui Han
- Abstract
- Presentation
Abstract
Background
Given the synergy effect of immunotherapy and anti-angiogenic therapy in advanced NSCLC, FDA approved atezolizumab plus bevacizumab and chemotherapy as first-line treatment. However, chemo-free first-line strategy of PD-1/PD-L1 inhibitor combining angiogenesis modulator remains to be explored. This is the first trial evaluating sintilimab (anti-PD-1) plus anlotinib (multi-target TKI against tumor angiogenesis and proliferation) in treatment-naive advanced NSCLC patients and is one arm of Phase I anlotinib-based trial (NCT03628521).
Methods
Treatment-naive, stage IIIB/IV NSCLC patients aged 18-75 with ECOG PS 0-1 were eligible. Patients with EGFR, ALK or ROS1 mutations were excluded. Participants were given intravenous sintilimab (200mg q3w) and oral anlotinib (12mg/d 2 weeks on/1 week off) until progression or unacceptable toxicity. The primary endpoints were ORR and safety. The secondary endpoints included DCR, PFS and OS. AEs were graded according to CTCAE v4.0.
Results
From September-2018 to February-2019, 22 patients were enrolled. Most were male (95.5%), former/current smokers (63.6%) and squamous cell histology (54.5%). 4 had baseline brain metastases. All patients have received at least once tumor assessment as of Jul-3th-2019. Among all, 16 achieved confirmed PR, 6 achieved SD, ORR was 72.7% (49.8%, 89.3%) and DCR was 100% (84.6%, 100%). 6 month PFS rate is 93.8% (95%CI: 63.23%, 99.10%). Overall, sintilimab and anlotinib was well tolerated. 6 (27.3%) had grade 3 and above treatment related adverse event (TRAE). The most common TRAE included fecal occult blood, hyperuricemia, hyponatremia, foot-hand syndrome, etc. 21 patients had baseline PD-L1-evaluated and 18 patients got TMB status (details in table). Notably, 5 of 6 SD patients developed cavities inside, suggesting a synergetic anti-tumor effect from combination regimen.Conclusion
In this interim analysis, sintilimab plus anlotinib showed high ORR (72.7%) and DCR (100%) with tolerable safety profile, supporting worthy of further development from this convenient chemo-free regimen in first line setting.
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MA01 - Oligometastatic Disease (ID 114)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Oligometastatic NSCLC
- Presentations: 1
- Now Available
- Moderators:Anne Marie Clasina Dingemans, Matthias Guckenberger
- Coordinates: 9/08/2019, 10:30 - 12:00, Copenhagen (1980)
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MA01.10 - Additional Local Consolidative Therapy Showed Survival Benefit Than EGFR-TKIs Alone in Bone Oligometastatic Lung Adenocarcinoma Patients (Now Available) (ID 398)
10:30 - 12:00 | Author(s): Baohui Han
- Abstract
- Presentation
Background
Whether epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs) plus local consolidative therapy (LCT) has better survival benefit than EGFR-TKIs alone remains controversial in lung adenocarcinoma patients with EGFR mutation and bone oligometastases.
Method
We conducted a retrospective study to assess the effects of LCT on bone oligometastases lung adenocarcinoma patients with EGFR mutation. The primary endpoint was overall survival (OS); The secondary endpoints was progression-free survival (PFS).
Result
A total of 127 lung adenocarcinoma patients with EGFR mutation and bone oligometastases were identified. There were 65 patients received EGFR-TKIs alone (monotherapy group) and 62 patients received EGFR-TKIs plus local consolidative therapy (LCT) (combination group). Addition of LCT was associated with a significantly longer OS (36.3 vs. 21.0 months, P=0.01, hazard ratio [HR]=0.537, 95% confidence interval [CI]:0.360-0.801, p=0.01) and PFS (14.0 vs. 8.1 months, P=0.01, HR=0.613, 95%CI: 0.427-0.879, p=0.01) in the whole cohort (Figure 1). All subgroups showed OS benefit in faver of combination therapy except for PS scores greater than or equal to 2 group, and all subgroups analyzed derived PFS benefit in favor of combination therapy (Figure 2).
Conclusion
In patients with EGFR-mutant lung adenocacinoma and bone oligometastases, LCT plus EGFR-TKIs therapy was associated with significantly longer OS and PFS than EGFR-TKIs therapy alone, indicating that LCT plus EGFR-TKIs therapy might be a better therapeutic option for those patient population.
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MA13 - Going Back to the Roots! (ID 139)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:Maurice Perol, Kaoru Kubota
- Coordinates: 9/09/2019, 14:00 - 15:30, Vancouver (2003)
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MA13.11 - A Randomized Phase III Study of Cisplatin-Polymeric Micelle Paclitaxel vs Cisplatin-Solvent-Based Paclitaxel in 1st Line Advanced NSCLC (Now Available) (ID 696)
14:00 - 15:30 | Author(s): Baohui Han
- Abstract
- Presentation
Background
Cisplatin-sb-Pac is the one of current standard of chemotherapy in aNSCLC, It produced 15% to 32% objective response rate (ORR) and 7.9 to 10.6 months of median overall survival (OS). Alternative nab-paclitaxel to sb-Pac only increased ORR but not improved progression-free survival (PFS) and OS. Thus the unmet medical need for new chemo regimen remains.
Method
From May 2015 to Jan 2018 448 untreated patients (pts) with stage IIIB to IV NSCLC from 24 sites were randomly assigned 2:1 to receive 230 mg/m2 pm-Pac and cisplatin 70 mg/m2 on day 1 of a 3-week cycle, and then dose escalation of pm-Pac to 300 mg/m2 from the second cycle if no prespecified toxic effects observed or 175 mg/m2 sb-Pac plus cisplatin 70 mg/m2 once every 3 weeks. Pts were stratified by stage and histology. The primary end point was ORR by Independent review committee (IRC) and Investigator (INV) in the intent-to-treat population. The second endpoints included PFS, OS and safety. Data cutoff was Jan 26, 2019.
Result
300 pts were assigned to pm-Pac and 148 to sb-Pac. Baseline characteristic were balance in both arms. Nonsquamous carcinoma (non-squ) and stage IV were 57.3% and 81.0% in pm-Pac and 58.1% and 81.8% in sb-Pac respectively. 73.2% pts in pm-Pac arm escalated their dose to 300mg/m2, 0.7% down to 184mg/m2. ORR and PFS in pm-Pac were significant better than that in sb-Pac (table 1). OS was immature. For histology subgroup the ORR was 58.6% v 37.1% (P=0.0054) in squamous carcinoma (Squ) and 44.2% v 18.6% (P<0.0001) in non-squ. Grade ≥3 AEs was 80.0% for pm-Pac and 79.7% for sb-Pac. No new safety issues were identified.
Conclusion
The phase 3 trial met its primary endpoint. pm-Pac significantly improved ORR and PFS than sb-Pac, and pm-Pac regimen should be a new standard chemo for aNSCLC. (NCT 02667743).
Tab. Efficacies comparison between pm-Pac and sb-Pac
pm-Pac
sb-Pac
P value
ORR % (95% CI)
IRC
INV
50.3 (44.5-56.1)
52.0 (46.2-57.8)
26.4 (19.5-34.2)
28.4 (21.3-36.4)
<0.0001
<0.0001
PFS (months)
6.4 (6.2-6.9)
5.3 (4.6-6.0)
HR 0.66 (0.52-0.84), P=0.0006
OS at 12 months
67.3%
61.8%
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MA25 - Precision Medicine in Advanced NSCLC (ID 352)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:Sebastian Defranchi, Karen Kelly
- Coordinates: 9/10/2019, 14:30 - 16:00, Dublin (1997)
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MA25.09 - Navigating Anlotinib Precision Therapy Through the Genetic Profiling of Circulating DNA in Non-Small Cell Lung Cancer Patients (Now Available) (ID 1055)
14:30 - 16:00 | Author(s): Baohui Han
- Abstract
- Presentation
Background
Anlotinib is an oral multi-targeted anti-angiogenic drug, and its clinical predictor for non-small cell lung cancer (NSCLC) patients is still elusive. The aim of this study is to screen predictor for anlotinib via non-invasive genetic profiling of plasma cell free DNA and circulating tumor DNA (cfDNA & ctDNA).
Method
Tumor-specific target capture to profile the circulating DNA of ALTER0303 (Evaluating NSCLC clinical anti-tumor efficacy through anlotinib therapy) study participants. Acquired mutations were screened out via comparing genetic profiling between baseline (BL) and progression disease (PD), and were used for anlotinib stratification. Based on the sequencing data at BL, tumor mutation index (TMI) was established from three independent predictors germline and somatic mutation burden (G+S MB), nonsynonymous and synonymous mutation burden (N+S MB) and unfavorable mutation score (UMS), and was used for predicting anlotinib responders. In addition, TMI combined with IDH1Exon4 mutation status also be examined for serving as predictor for anlotinib stratification.
Result
Our data firstly indicated no benefit (NB, PFS ≤ 45 days) patients can be mainly excluded via analysis of ARID1A and BRCA2 genetic profiling. Secondly, for the no durable benefit (NDB, 45 days < PFS ≤ 130 days) and durable clinical benefit (DCB, PFS > 130 days) patients, harboring lower mutation burden (G+S MB, N+S MB, and UMS) received more benefit from anlotinib therapy. Subsequently, we found the predictor-TMI can predict anlotinib responders upon discovery cohort (Median PFS: 210 days vs 126 days; p = 0.0238; AUC = 0.77), and validation cohort (Median PFS: 210 days vs 127 days; p = 0.0352) and all patients (Median PFS: 210 days vs 127 days; p = 0.0044) more effectively. Furthermore, the IDH1Exon4 mutation was identified as an unfavorable factor to anlotinib therapy under TMI-based stratification. Lastly, the TMI plus IDH1Exon4 mutation status predict response to anlotinib significantly (Median PFS: 210 days vs 127 days, p < 0.0001, AUC = 0.90; Median OS: 423 days vs 162 days, p < 0.0001, AUC = 0.80).
Conclusion
This study provides circulating DNA sequencing-based stratification for underlying anlotinib responders via non-invasive approach, and thus potentially improve clinical outcome for NSCLC patients at 3rd line.
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OA03 - Systemic Therapies for SCLC: Novel Targets and Patients' Selection (ID 121)
- Event: WCLC 2019
- Type: Oral Session
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Now Available
- Moderators:Christine Lee Hann, Makoto Nishio
- Coordinates: 9/08/2019, 13:30 - 15:00, Hilton Head (1978)
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OA03.02 - Effect of Anlotinib in Advanced Small Cell Lung Cancer Patients Previously Received Chemoradiotherapy: A Subgroup Analysis in ALTER 1202 Trial (Now Available) (ID 1698)
13:30 - 15:00 | Author(s): Baohui Han
- Abstract
- Presentation
Background
The ALTER 1202 trial showed significant improvement in progress-free survival and well tolerant with anlotinib in advanced small cell lung cancer (SCLC) patients received at least two lines chemotherapy. Here, we reported the effect of anlotinib in patients previously received chemoradiotherapy.
Method
The ALTER 1202 was a randomized, double-blind phase 2 trial conducted at 11 centers in China. Patients with advanced SCLC that received at least two previous lines of chemotherapy were enrolled and randomized in a 2:1 ratio to receive either anlotinib or placebo until tumor progression or unacceptable toxicity. The subgroup analysis assessed the effect of anlotinib in patients with previous concurrent, sequential and alternate chemoradiotherapy. The primary outcome was progressive-free survival (PFS). The secondary outcomes were overall survival (OS), objective response rate, disease control rate and safety. Data are reported as per the 30 June 2018, data cutoff date. This trial is registered with ClinicalTrials.gov, number NCT03059797.
Result
Between March 30, 2017 and June 8, 2018, a total of 120 patients who met all eligibility criteria were randomly assigned to the anlotinib group (82 patients) or placebo group (38 patients). And 46 patients in anlotinib group and 22 patients in placebo group previously received chemoradiotherapy. Among them, the median PFS was 5.49 months (95% confidence interval [CI], 2.83 to 6.47) with anlotinib versus 0.69 months (95% CI, 0.66 to 0.76) with placebo (hazard ratio [HR], 0.14; 95% CI, 0.07 to 0.28; P<0.0001). Meanwhile, anlotinib significantly prolonged OS compared with placebo (9.49 months [95% CI, 7.29 to 12.68] versus 2.56 months [95% CI, 0.49 to 5.22]; HR, 0.46 [95% CI, 0.22 to 0.98]; P=0.0388) in patients previously received chemoradiotherapy. The most common adverse events were hypertension (39.13%), weight loss (39.13%), hypertriglyceridemia (36.96%) and leukopenia (30.43%). While, the most common grade 3 or worse adverse events were hypertension (15.22%), hypertriglyceridemia (10.87%), γ-glutamyl-transferase increased (8.70%).
Conclusion
Anlotinib improved PFS and OS in advanced SCLC patients previously received chemoradiotherapy and was well tolerated.
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OA11 - Decomplexifying Molecular Targets, Immunotherapy and Treatment Settings in the Real World (ID 137)
- Event: WCLC 2019
- Type: Oral Session
- Track: Treatment in the Real World - Support, Survivorship, Systems Research
- Presentations: 1
- Now Available
- Moderators:Kumar Prabhash, Jyoti D Patel
- Coordinates: 9/09/2019, 14:00 - 15:30, Interlaken (1988)
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OA11.07 - Chemotherapy Plus EGFR-TKI as First-Line Treatment Provides Better Survival for EGFR Mutation NSCLC Patients: Update Data for NCT02148380 (Now Available) (ID 2207)
14:00 - 15:30 | Author(s): Baohui Han
- Abstract
- Presentation
Background
Previously, we did a prospective study to compare pemetrexed plus carboplatin and gefitinib to either pemetrexed plus carboplatin or gefitinib alone as first-line therapy for lung adenocarcinoma patients harboring sensitive EGFR mutations (NCT02148380). The primary endpoint PFS was met at Oct 1, 2016. However, the OS of combinational group was not mature then [Han B, et al. Int J Cancer. 2017;141:1249-1256]. In the present study, we continued the OS follow-up until Sep 28 2018.
Method
The survival curves for OS were estimated with the Kaplan-Meier method and were compared between combination and gefitinib groups using the log-rank test. 2-years, 3-years survival rates were compared between combination and gefitinib groups using Pearson Chi-Square.
Result
Baseline characteristics of the intent-to-treat (ITT) population have been reported. At last day of follow-up (Sep 28 2018), 30 (75.0%) patients in the combinational group, 35 (85.4%) patients in the gefitinib group died. 2-year survival rates of combinational and gefitinib groups were 85.0% (34/40), 56.1% (23/41) (P=0.004), respectively. 3-year survival rates of combinational and gefitinib groups were 52.5% (21/40), 24.4% (10/41) (P=0.009), respectively. The median OS was 37.9 months (95%CI: 17.3-58.6) for the combinational group, which was substantially longer than the median OS for first-line gefitinib group (25.8 months [95%CI: 19.2-32.3]). The HR of combinational group versus gefitinib group was 0.56 (95%CI:0.34-0.91, P=0.02).
19del: The median OS was 51.0 months (95%CI: 36.6-65.5) for the combinational group, which was substantially longer than the median OS for first-line gefitinib group (29.8 months [95%CI: 26.7-32.9]). The HR of combinational group versus gefitinib group was 0.61 (95%CI:0.30-1.25, P=0.18).
21L858R: The median OS was 32.3 months (95%CI: 27.8-36.7) for the combinational group, which was substantially longer than the median OS for first-line gefitinib group (22.8 months [95%CI: 13.1-32.5]). The HR of combinational group versus gefitinib group was 0.50 (95%CI:0.25-1.00, P=0.05).
Totally, 15 patients had baseline central nervous system (CNS) metastases. The median OS of patients who had baseline CNS metastases was 25.6 months (95%CI: 15.1-36.1); the median OS of patients who had no baseline CNS metastases was 31.7 months (95%CI: 28.2-35.2). The HR of CNS metastases group versus no CNS metastases group was 2.80 (95%CI:1.51-5.18, P=0.001). Among the combinational group, 20% (8/40) percent of patients had baseline CNS metastases. 17.1% (7/41) percent of patients in the gefitinib group had baseline CNS metastases.
CNS: The median OS was 27.0 months, (95%CI: 21.8-32.3) for the combinational group, which was substantially longer than the median OS for first-line gefitinib group (15.5 months, 95%CI: 6.8-24.3). The HR of combinational group versus gefitinib group was 0.17 (95%CI:0.04-0.68, P=0.013).
No CNS: The median OS was 47.4 months, 95%CI: 27.2-67.7 for the combinational group, which was substantially longer than the median OS for first-line gefitinib group (27.4 months, 95%CI: 23.0-33.7). The HR of combinational group versus gefitinib group was 0.57 (95%CI:0.32-0.99, P=0.044).
Conclusion
The current study on lung adenocarcinoma patients harboring sensitive EGFR mutations showed that the combined treatment with pemetrexed plus carboplatin with gefitinib provide better survival benefits than gefitinib alone.
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-03 - Efficacy and Safety of Biosimilar QL1101 Compared with Avastin in Patients with Non-Squamous Non-Small Cell Lung Cancer (ID 738)
09:45 - 18:00 | Presenting Author(s): Baohui Han
- Abstract
Background
QL1101 is a biosimilar molecule of bevacizumab (BEV, Avastin®), a monoclonal antibody (mAb) that binds and inhibits vascular endothelial growth factor (VEGF).The main purpose of the study is to evaluate whether the effectiveness of QL1101 is bioequivalent to that of Avastin®, and the secondary purpose is to evaluate the bioequivalence on safety and immunogenicity between QL1101 and Avastin®.
Method
Total 512 patients with locally metastatic or recurrent non-squamous cell non-small cell lung cancer were planned to recruit in the study (NCT03169335). The patients were divided into QL1101 (test group) or Avastin® (control group) at 1:1 ratio in combination respectively with paclitaxel/carboplatin (paclitaxel 175mg/m2, carboplatin AUC=5). QL1101 or Avastin was given every 3 weeks as one treatment cycle for 6 cycles with the same dose of 15mg/kg per time, then followed by QL1101 single-drug maintenance treatment. The primary endpoint was the best objective response rate (ORR) at week 18 as evaluated by the blind independent imaging review committee, and the secondary endpoints include DOR, PFS and OS.
Result
A total of 675 subjects were screened and 532 were finally enrolled and treated including 266 in the trial group and 266 in the control group. At week 18, the ORR of the QL1101 group and Avastin group were 52.26% (CR: 0, PR: 139) and 56.02% (1 cases CR, 148 PR), respectively, and risk ratio (RR) value and 90% CI was 0.933 (0.818-1.064), which met the pre-specified equivalence margins (0.75-1.33). The mDOR in QL1101 group and Avastin group was 5.88 and 6.93 month (P=0.5044）respectively, and mPFS were 7.88 and 8.34 months (P=0.2760) accordingly, the 12-month OS in the two groups was 69.18% and 75.10% respectively. The incidence of CTCAE≥ grade 3 adverse events was 31.20 % in QL1101 group and 24.06 % in Avastin group, respectively (P = 0.0808). The immunogenicity (ADA and Nab tested) of the two groups was similar.
Conclusion
QL1101 and Avastin are equivalent in clinical efficacy, and the safety profile (including immunogenicity) is quite similar in patients with non-squamous cell non-small cell lung cancer. There are no unexpected serious adverse reactions were found during the study.
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P1.01-95 - Efficacy and Safety of Anlotinib in Combination with Chemotherapy as First-Line Therapy in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients (ID 2296)
09:45 - 18:00 | Author(s): Baohui Han
- Abstract
Background
Anlotinib (AL3818) is a novel multi-target angioenesis TKI targeting the VEGFR, FGFR, PDGFR and c-Kit. In the ALTER0303 trial, Anlotinib as third-line treatment significantly improved progress-free survival (PFS) and overall survival (OS) in advanced NSCLC patients. This is the first trial evaluating the combination of chemotherapy and anlotinib in treatment-naive advanced NSCLC and is one arm of Phase II anlotinib-based trial (NCT03628521).
Method
Patients with previously untreated EGFR/ALK/ROS1 negative advanced NSCLC were enrolled. Eligible patients received anlotinib (12 mg QD from day 1 to 14 of a 21-day cycle) combined with carboplatin (AUC 5) and pemetrexed (adenocarcinoma, 500mg/m2)/gemcitabine (squamous, 1.0g/m2，day1&8) for four to six cycles (21-day cycle). Maintenance treatment was followed by using pemetrexed and anlotinib (anlotinib alone for squamous) until disease progression or treatment intolerance. The primary outcome was objective response (ORR) and secondary outcomes were PFS, disease control rate (DCR) and OS.
Result
Until the 21st March 2019, the curative effect was assessed in 30 enrolled patients according to the RECIST 1.1. Among these patients, eighteen of them achieved PR (all confirmed), eleven of them achieved SD and only one patient developed to disease progression. The objective response rate was 60.0 % while the disease control rate was 96.7 %. The most common Grade 3 adverse events were decreased platelet count (20 %), hypertriglyceridemia (10 %) and oral mucositis (6.67 %). 3 patients showed Grade 4 decrease of platelet count (10 %), and both of them belong to the gemcitabine group.
Conclusion
The combination of anlotinib and chemotherapy showed the potential effect and a manageable safety profile in patients with previously untreated EGFR/ALK/ROS1 negative advanced NSCLC.
Table 1: Response rates
Response
Assessed
CR
0
PR
18/30（60.0%）
SD
11/30（36.7%）
PD
1/30 （3.3%）
ORR, n/N（%）
18/30 （60.0%）
DCR, n/N（%）
29/30 （96.7%）
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P1.04 - Immuno-oncology (ID 164)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.04-02 - Efficacy and Safety of Sintilimab with Anlotinib as First-Line Therapy for Advanced Non-Small Cell Lung Cancer (NSCLC) (ID 939)
09:45 - 18:00 | Presenting Author(s): Baohui Han
- Abstract
Background
Given the synergy effect of immunotherapy and anti-angiogenic therapy in advanced NSCLC, FDA approved atezolizumab plus bevacizumab and chemotherapy as first-line treatment. However, chemo-free first-line strategy of PD-1/PD-L1 inhibitor combining angiogenesis modulator remains to be explored. This is the first trial evaluating sintilimab (anti-PD-1) plus anlotinib (multi-target TKI against tumor angiogenesis and proliferation) in treatment-naive advanced NSCLC patients and is one arm of Phase I anlotinib-based trial (NCT03628521).
Method
Treatment-naive, stage IIIB/IV NSCLC patients aged 18-75 with ECOG PS 0-1 were eligible. Patients with EGFR, ALK or ROS1 mutations were excluded. Participants were given intravenous sintilimab (200mg q3w) and oral anlotinib (12mg/d 2 weeks on/1 week off) until progression or unacceptable toxicity. The primary endpoints were ORR and safety. The secondary endpoints included DCR, PFS and OS. AEs were graded according to CTCAE v4.0.
Result
From September-2018 to February-2019, 22 patients were enrolled. Most were male (95.5%), former/current smokers (63.6%) and squamous cell histology (54.5%). 4 had baseline brain metastases. All patients have received at least once tumor assessment as of Jul-3th-2019. Among all, 16 achieved confirmed PR, 6 achieved SD, ORR was 72.7% (49.8%, 89.3%) and DCR was 100% (84.6%, 100%). 6 month PFS rate is 93.8% (95%CI: 63.23%, 99.10%). Overall, sintilimab and anlotinib was well tolerated. 6 (27.3%) had grade 3 and above treatment related adverse event (TRAE). The most common TRAE included fecal occult blood, hyperuricemia, hyponatremia, foot-hand syndrome, etc. 21 patients had baseline PD-L1-evaluated and 18 patients got TMB status (details in table). Notably, 5 of 6 SD patients developed cavities inside, suggesting a synergetic anti-tumor effect from combination regimen.
Conclusion
In this interim analysis, sintilimab plus anlotinib showed high ORR (72.7%) and DCR (100%) with tolerable safety profile, supporting worthy of further development from this convenient chemo-free regimen in first line setting.
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P2.01 - Advanced NSCLC (ID 159)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 4
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.01-21 - Efficacy and Safety of Combing Anlotinib and Erlotinib as a First-Line Therapy in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) (ID 2361)
10:15 - 18:15 | Author(s): Baohui Han
- Abstract
Background
As a promising multi-target tyrosine kinase inhibitor (TKI), anlotinib hydrochloride significantly improved overall survival (OS) and progression-free survival (PFS) in advanced NSCLC patients in the phase 3 trial ALTER0303. Antiangiogenesis therapy combined with EGFR-TKI has shown excellent efficacy and survival benefits in patients with EGFR mutations. This is the first trial evaluating anlotinib plus erlotinib in treatment-naive advanced NSCLC patients and is one arm of Phase II anlotinib-based trial (NCT03628521).
Method
Patients with previously untreated, EGFR mutation–positive (exon 19 deletion or L858R) advanced NSCLC were enrolled. Eligible patients received anlotinib (10 mg QD from day 1 to 14 of a 21-day cycle) combined with erlotinib (at a dose of 150 mg once daily) until disease progression or treatment intolerance. The primary outcome was objective response (ORR) and secondary outcomes were PFS, disease control rate (DCR) and OS.
Result
Until the 21st March 2019, 26 patients were enrolled. All are under treatment and 17 have received at least one tumor assessment. Among these patients, fifteen of them achieved PR (9 confirmed, the rest waiting for next assessment), two of them achieved SD and no patient developed to disease progression. The objective response rate was 88.2 % while the disease control rate was 100 %.The most common Grade 3 TRAE were rash (15.38 %), oral mucositis (11.54%) and albuminuria (7.69 %), and no grade 4/5 observation.
Conclusion
The combination of anlotinib and erlotinib showed the promising efficacy for previously untreated, EGFR mutation–positive advanced NSCLC patients with a manageable safety profile.
Table 1: Response rates
Response
Assessed
CR
0
PR
15/17（88.2%）
SD
2/17（11.76%）
PD
0
ORR, n/N（%）
15/17 (88.2%)
DCR, n/N（%）
17/17 (100.0%)
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P2.01-23 - DUBLIN-3, a Phase (Ph) III Trial Comparing the Plinabulin (P)/Docetaxel(D) Combination with D Alone in Stage IIIb/IV NSCLC (Now Available) (ID 476)
10:15 - 18:15 | Author(s): Baohui Han
- Abstract
Background
In 2018, practice patterns changed in untreated metastatic NSCLC, as platinum-based chemotherapy (Chemo) started to be combined with pembrolizumab. Prior to 2018, checkpoint inhibitors (C-I) were given sequentially with Chemo. In C-I refractory metastatic NSCLC, single agent D is standard of care. Although effective, D induces AEs (Neutropenia (N) that may require dose reduction to sub-therapeutic levels. The addition of Plinabulin (P) to D (D+P) reduced D-induced grade 4 (Gr4) N (frequency of 33% vs 5% for D vs D+P; p<0.0003) and thrombocytopenia (P<0.02) vs D alone (Blayney ASH 2018; IASLC 2018) in Ph 2. Importantly, P added to D improved median overall-survival (OS) with 4.6-month, and duration of response (DoR) with 1-year (p<0.05) vs D alone (Mohanlal ASCO-SITC 2017) in pts with a measurable lesion (per RECIST 1.1) located in the lung. P induces Dendritic Cell (DC) maturation and CD40 upregulation and facilitates DC-dependent T-cell proliferation in an antigen (Ag) specific manner (Lloyd AACR 2016). Therefore, P is predicted to be the most effective in a setting that harbors novel Ags, that can stimulate the immune system. Subclonal lung lesions can induce novel Ags (De Bruin Science 2014), but clonal lung lesions can also harbor Ags that can stimulate the immune system, as long as immune tolerance is not yet developed. There is a high concordance in mutation status (thus Ags) between clonal primary and metastatic lesions in NSCLC (Sherwood J Exp & Clin Canc Res 2015), but the distant lesions had more time to induce immune tolerance development. Hence, we required the presence of measurable lesion present in the lung in DUBLIN-3. We combined P with D since D can release Ags which in turn can be presented by P-modulated DCs to cytotoxic CD8 T-cells.
Method
DUBLIN-3 (NCT02504489), is an ongoing global PhIII study in EGFR wild-type advanced or metastatic NSCLC pts (target n=554) receiving 2nd- or 3rd-line systemic therapy with D+P or D in a 1:1 ratio. The primary endpoint is OS. Key secondary endpoints are incidence of Gr 4 N on day 8 of Cycle 1, D dose modification due to N, QoL (EORTC QLQ-C30), ORR, PFS, and DoR. The study is single-blinded (for pts) to more reliable allow for QoL assessments. Pts must have at least one measurable lesion located in the lung and must have failed a prior platinum-based regimen. Prior PD1/PD-L1 use is allowed. A pre-specified first Interim Analysis (IA) occurred at reaching ~150 events and a second pre-specified IA is to occur at ~ 300 events.
Result
~400 patients have been enrolled to date with more than 200 events achieved. Based on the data at the 1st IA, the study will continue, unmodified, to the 2nd IA.
Conclusion
The D+P combination holds the promise of a novel 2nd or 3rd line treatment option with superior efficacy and safety over D alone. The 2nd IA of DUBLIN-3 is expected to occur later in 2019.
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P2.01-31 - Preliminary Results of Second Generation ALK Inhibitor PLB1003: A Phase La Study (Now Available) (ID 1741)
10:15 - 18:15 | Presenting Author(s): Baohui Han
- Abstract
Background
ALK rearrangements have been described in approximately 4-5% of patients with non-squamous non-small cell lung cancer (NSCLC). Crizotinib is initially effective in the treatment of ALK-rearranged NSCLC, but the disease eventually progresses. PLB1003, a high-efficiency second generation ALK inhibitor, was developed due to the increased resistance of EML4-ALK fusion genes. Preclinical data show that PLB1003 is safe and effective in cell-based assays and Crizotinib-resistant animal models. This is the ongoing phase Ia study of PLB1003.
Method
An open-label, multicenter phase I clinical trial was conducted in patients with locally advanced or metastatic NSCLC who had previously failed or were intolerable to Crizotinib or chemotherapy. It consisted of dose-escalation cohorts and dose-expansion cohorts. In the dose-escalation cohorts, patients were orally given 50-500mg/d of PLB1003 at 6 dose levels . In each cohort, patients' plasma were collected for pharmacokinetic evaluation. The safety, tolerability, pharmacokinetics, maximum tolerated dose (MTD), dose limiting toxicities (DLT) and recommended phase 2 dose (RP2D) of PLB1003 were determined.
Result
A total of 21 patients were enrolled in dose-escalation cohorts as of 31 August 2018. The dose-escalation cohort is ongoing at the dose of 200 and 250 mg BID. A lipase elevation of DLT event was observed at 250 mg BID. MTD has not been reached in this study. Additionally, the most common treatment-emergent adverse events (TEAEs) (>10%) were grade1/2, including: (1) gastrointestinal toxicities: diarrhea (24%), vomiting (14%); (2) hepatotoxicity: increased GGT (g-glutamyltransferase) (48%), increased ALP (33%), elevated ALT (43%) and AST (33%); (3) others: increased blood glucose level (43%), hyperuricemia (24%), increased creatinine (19%), anemia (19%), hypercholesterolemia (14%). All the treatment-related adverse events (TRAEs) were reversible. TRAEs of grade 3, increasing of GGT (-glutamyl transferase) (33%), alkaline phosphatase (10%) and lipase (10%) , mostly appeared during 7-13 weeks of initial study. Patients all recovered from TRAEs of grade 3 with symptomatic treatments. Among the 14 evaluable patients in ≥200mg/d cohorts, 10 patients had PR (71%), 2 patients had SD (14%), and the disease control rate (DCR) was 86%. Among the 7 patients who progressed with previous treatment of Crizotinib, 5 patients had PR (71%), 1 patient had SD (14%), and the DCR was 86%.
Conclusion
PLB1003 is safe, tolerable and has potential clinical benefit to locally advanced or metastatic NSCLC patients with ALK rearrangement mutation and had disease progression or were intolerable to previously treatment of Crizotinib or chemtherapy. (ClinicalTrials.gov number, NCT03130881)
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P2.01-85 - Schwann Cells Are Overexpressed and Inversely Correlated with Survival of Non-Small Cell Lung Cancer Patients (ID 497)
10:15 - 18:15 | Author(s): Baohui Han
- Abstract
Background
The lungs are densely innervated by the peripheral nervous system (PNS). We have recently reported the presence of schwann cells(SCs), the principal glial cells of the PNS, in the murine and human lungs and the mechanisms by which tumor–neuroglia interaction affect lung cancer growth and metastasis(Cancer Research. 2018;78(20):5927-39). Nevertheless, the clinical epidemiological characters of the innervation of lung cancer has not been intensively investigated.This study aimed to complement this vacancy by determining the prevalence of SCs expression in NSCLC and analyzing its associations with clinical pathologic parameters and outcome.
Method
Totally, 141 operated patients at stage I-III NSCLC were enrolled. Formalin-fixed and paraffin-embedded (FFPE) tumour sections were reviewed and stained with glia-specific antibodies S100b, GFAP and P75NTR. The correlations between expression of SCs and clinical pathologic features, overall survival (OS) and recurrence free survival(RFS) were analyzed.
Result
No significant relationship were found between SCs expression and patients’gender, age, smoking history, subtype or EGFR status. Interestingly, SCs expression was markedly increased in cancer tissues compared with in adjacent tissues. Furthermore, SCs were significantly overexpressed in tumors of stage II-III than in stage I(P<0.01). Kaplan-Meier curve analysis revealed that high expression of SCs was negatively associated with longer RFS (P<0.001) and OS(P<0.001).5 year-RFS were 18.8%(High) and 51.8%(Low) respectively.
Conclusion
High expression of SCs is negatively correlated with tumor stage and survival, indicating its potential diagnostic and therapeutic value for operated NSCLC patients.
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P2.03 - Biology (ID 162)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.03-49 - Roles of CENPU in Lung Adenocarcinoma Progression and Invasion (Now Available) (ID 1382)
10:15 - 18:15 | Author(s): Baohui Han
- Abstract
Background
Centromere protein U (CENPU), a centromere protein mediating kinetochore-microtubule interaction, is critical for proper cell cycle and mitosis. It has been implicated that CENPU promotes tumorigenesis in variant malignancies. However, roles of CENPU in lung adenocarcinoma progression and underlying mechanisms remain to be elucidated.
Method
CENPU expression in 90 pair lung adenocarcinoma/adjacent normal lung samples was examined with immunohistochemistry (IHC). Then CENPU expression was inhibited with lentiviral-mediated shRNA strategy in human lung adenocarcinoma cell line H1299 to examine the impact of CENPU knockdown for lung adenocarcinoma progression and metastasis. Cell proliferation, colony formation, cell cycle and cell survival were analyzed by Cellomics cell counting method, colonogenesis assay, PI and Annexin V-APC staining respectively while cellular migration and invasion were determined by cell scratch and transwell test. Furthermore, expression of critical factors involved in epithelial-to-mesenchymal transition (EMT) were determined with western blot.
Result
CENPU expression was significantly increased in lung adenocarcinomas as compared to adjacent normal lung tissues (fold change=8.54, P<0.0001) (Fig. 1A). Functionl analysis revealed that in human lung adenocarcinoma cell line H1299, CENPU knockdown impaired cell proliferation (Fig. 1B), inhibited colony formation ability (Fig. 1C) and induced cell cycle arrest (Fig. 1D). Additionally, cellular migration and invasion was also inhibited by CENPU knockdown (Fig. 1E-F). It is further shown that E-Cadherin was induced while N-Cadherin and vimentin were inhibited by CENPU knockdown (Fig. 1G), indicating that CENPU was important for EMT process and cancer metastasis.
Conclusion
It showed that CENPU expression is significantly upregulated lung adenocarcinoma tissue. Functional analysis indicated that CENPU is critical for cell proliferation, survival, migration and metastasis in lung adenocarcinoma cell line H1299. CENPU represents a promising target for lung adenocarcinoma therapy.
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P2.11 - Screening and Early Detection (ID 178)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.11-18 - Circulating Serum KLK5 and L1CAM Levels Potentially Predict Clinical Outcome to Anlotinib Therapy in NSCLC Patients (ID 1074)
10:15 - 18:15 | Author(s): Baohui Han
- Abstract
Background
Anlotinib is an oral multi-targeted tyrosine kinase inhibitor (TKI), which has been demonstrated to be effective upon non-small cell lung cancer (NSCLC) in clinical trials at 3rd line. However, the underlying anlotinib-responsive patients remain elusive. In the present study, we aimed to screen out the potential biomarkers for anlotinib-responsive stratification via transcriptome analysis.
Method
Anlotinib-resistant NCI-H1975 cells were established in vitro. Toxicologic effects undergoing anlotinib stress were observed upon NCI-H1975 cells and anlotinib-resistant NCI-H1975 cells, respectively. Transcriptome profiling was performed to screen anlotinib resistance-associated genes between NCI-H1975 cells and anlotinib-resistant NCI-H1975 cells. The correlations between mRNA levels of the anlotinib resistance-associated genes and clinical outcomes of NSCLC patients were analyzed via Kaplan-Meier survival analysis in TCGA cohort. Potential biomarkers for anlotinib-responsive stratification were examined in a 28 patients’ cohort of anlotinib clinical trial (NCT02388919).
Result
Anlotinib-induced cytotoxic effects nearly disappeared in anlotinib-resistant NCI-H1975 cells, which are majority attributed to the modulated gene expression of multiple biological processes. Among these biological processes, angiogenesis plays an important role in anlotinib resistance. Up-regulation of angiogenesis-related KLK5 and L1CAM are mostly associated with poor clinical outcome in NSCLC patients. Knockdown of KLK5 and L1CAM contribute to increase anlotinib-induced cytotoxicity upon NCI-H1975 cells and anlotinib-resistant NCI-H1975 cells. High serum levels of KLK5 and L1CAM are also associated with poor anlotinib response in NSCLC patients at 3rd line.
Conclusion
This study suggested that serum levels of KLK5 and L1CAM potentially serve as biomarkers for anlotinib-responsive stratification in NSCLC patients at 3rd line.
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P2.12 - Small Cell Lung Cancer/NET (ID 180)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Small Cell Lung Cancer/NET
- Presentations: 2
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.12-11 - Quality of Life in ALTER1202 Trial of Anlotinib as Third-or Further Line Therapy for Advanced Small Cell Lung Cancer (SCLC): A Post-Hoc Analysis (ID 1300)
10:15 - 18:15 | Author(s): Baohui Han
- Abstract
Background
Anlotinib significantly improved progress-free survival of advanced small cell lung cancer (SCLC) patients in ALTER1202 trial. In this post-hoc analysis, we assessed the effect of anlotinib on health-related quality of life in ALTER1202 trial.
Method
In the randomised, phase 2, multicentre ALTER1202 trial, patients with advanced SCLC that received at least two previous lines of chemotherapy were enrolled from 11 centers in China. Eligible patients were randomly assign (2:1) to receive anlotinib or placebo. Health-related quality of life was assessed by EQ-5D scores. Patients filled out questionnaires at screening period and the end of each treatment cycle.
Result
Between March 30, 2017 and June 8, 2018, a total of 120 patients were enrolled. There were 119 patients with completed questionnaires at screening period, and 106 patients completed questionnaires at the end of the first treatment cycle (76 in anlotinib group, 30 in placebo group). EQ-5D scores had no significant difference between baseline and the end of the first treatment cycle in patients with anlotinib (0.85 versus 0.85, P=0.706). The median EQ-5D VASscores were 80.0 versus 85.0 in anlotinib and placebo group respectively (P=0.323) at screening period, and 90.0 versus 82.5 at the end of the first treatment cycle (P=0.273). The change of EQ-5D VAS scores from baseline to the end of the first treatment cycle was statistically significant (P=0.001) in patients with anlotinib compared to patients with placebo.
Conclusion
This post-hoc analysis showed that anlotinib maintained health-related quality of life in advanced SCLC patients.
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P2.12-26 - The Impact of Anlotinib for Relapsed SCLC Patients with Brain Metastases: A Subgroup Analysis of ALTER 1202 (ID 489)
10:15 - 18:15 | Author(s): Baohui Han
- Abstract
Background
ALTER1202 trial (NCT03059797), a multicentre, randomized, double-blind phase II study has demonstrated that anlotinib significantly prolonged progress-free survival (PFS) in relapsed SCLC patients as 3rdor further line treatment. Here, we performed a comparative analysis for patients with brain metastases in the placebo and anlotinib arms.
Method
Eligible either limited- or extensive-stage SCLC pts who failed ≥2 lines of chemotherapy (n=120) were randomized 2:1 to receive anlotinib or placebo (12 mg QD from day 1 to 14 of a 21-day cycle) till progression or intolerable toxicity. The primary endpoint was PFS. This subgroup analysis was based on patients with brain metastases at baseline.
Result
There are 30 pts with brain metastases in anlotinib and placebo groups (n=21 vs 9). Anlotinib significantly improved PFS (3.84 vs 0.76 months; HR = 0.15; 95% CI, 0.04–0.51; P = 0.0005) and OS (6.08 vs 2.56 months; HR = 0.26; 95% CI, 0.09–0.73; P = 0.0061) comparing to placebo in patients with brain metastases at baseline. In anlotinib group, loss of appetite (47.62%), loss of weight (42.86 %), leukopenia (38.10%) and hypertriglyceridemia (38.10%) were the most common adverse events (AEs); then, in placebo group were emesis (44.44%) and loss of appetite (33.33 %).
Conclusion
For patients with brain metastases in ALTER1202 trial, significant improvement in OS and PFS were found in anlotinib treated group with a manageable safety profile.
