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Tao Jiang
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JCSE01 - Joint IASLC-CSCO-CAALC Session (ID 63)
- Event: WCLC 2019
- Type: Joint IASLC-CSCO-CAALC Session
- Track:
- Presentations: 1
- 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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JCSE01.26 - PD-1 Inhibitor Plus Chemotherapy as 2nd/Subsequent Line Setting Demonstrate Superior Efficacy over PD-1 Inhibitor Alone in Pts of Advanced NSCLC (ID 3863)
07:00 - 11:15 | Author(s): Tao Jiang
- Abstract
Abstract
Background
PD-1/PD-L1 inhibitors have become standard of care as the 2nd-line setting and also approved as 1st line setting when combined with doublet chemotherapy in patients with advanced NSCLC. This study aims to compare the efficacy of PD-1 inhibitor plus chemotherapy with PD-1 inhibitor alone as 2nd/subsequent lines setting in patients with advanced NSCLC
Methods
Patients who received PD-1 inhibitor monotherapy or PD-1 inhibitor plus chemotherapy as 2nd/subsequent lines setting in Shanghai Pulmonary Hospital, Tongji University were retrospectively collected. Detailed clinicopathologic characteristics and therapeutic outcomes were analysis.
Results
From January 2016 to February 2019, 148 patients who meet the criteria were included. Among them, 116 were in PD-1 inhibitor monotherapy group and 32 were in PD-1 inhibitor plus chemotherapy group. Chemotherapy regimens were pemetrexed(n=9), docetaxel(n=2), nab-paclitaxel(n=18) and gemcitabine(n=3). The baseline characteristics such as age, gender, smoking status, histology, PD-1 mono-antibodies, line of therapy were similar in the 2 groups. Combination group showed a favorable ORR (28.1% vs. 13.8%, p=0.055) and a significantly longer PFS(median 4.9 vs 2.5 months, p=0.005) compared with ICI monotherapy. Overall survial (OS) data was immature in the cutoff date of follow up. In the subgroup of 96 patients (monotherapy group n=69/ Combination group n=27) who were included as 2nd line setting, PD-1 inhibitor plus chemotherapy had significantly higher ORR(ORR:33.3% vs 18.8%, p=0.129) and longer PFS(median PFS: 4.9 vs 2.9 months, p=0.041).
Conclusion
PD-1 inhibitor plus chemotherapy as 2nd/subsequent lines setting demonstrated superior efficacy over PD-1 inhibitor alone in patients with advanced NSCLC.
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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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P1.01-121 - Superior Outcomes of 1<sup>st</sup> Line EGFR TKI in Next-Generation Sequencing Identified Uncommon EGFR Exon 19delins Mutation Non-Small Cell Lung Cancer (ID 2953)
09:45 - 18:00 | Author(s): Tao Jiang
- Abstract
Background
First line EGFR-TKI showed promising efficacy on EGFR mutant advanced non-small cell lung cancers (NSCLC). However, the response duration time differs with different mutation variants. The aim of our study was to evaluate the efficacy and resistance mechanism of first-line EGFR TKI in NSCLC patients with uncommon mutation of EGFR 19del mutations.
Method
Among 1530 lung cancer patients who received detection of next generation sequencing (NGS) from Jan, 2015 to Aug, 2018, 49 gefitinib or erlotinib treated EGFR exon 19delins mutant advanced NSCLC patients received NGS of 168 genes panel using tumor tissue in baseline was enrolled in this study for cohort A. Using Propensity Score Matching (Ratio of 1:2), 98 patients carrying EGFR sensitive mutation of EGFR exon19del (745-760del) were set as cohort B. EGFR exon 19delins mutation variants in cohort A, clinical outcomes and resistance mechanism for both cohorts were also been evaluated.
Result
Conclusion
In cohort A, 19 EGFR exon 19delins variants were detected and 10 variants were novel. Among exon 19 delins variants, L747-A750delinsP and L747-A753delinsS were the domain variants, contributing to 24.5% (12/49) and 22.5% (11/49) respectively. In cohort A, 38 patients were evaluated with progress disease and 11 patients were ongoing current treatments. In cohort B, 73 patients were evaluated with progress disease and 36 patients were ongoing current treatments. There was no difference between cohort A and B for base characteristics, treatment drugs and response rate. The median PFS of cohort A and B was 19.0 months vs. 12.0 months (p=0.006). In all the 19del variants, the mPFS of L747-A750delinsP subtype was significantly prolong for 21 months (p=0.03). All the progress disease patients received re-biopsy and NGS detection. T790M was defined as the domain acquired resistance mechanism, contributing to 26.3% in cohort A and 45.2% in cohort B, followed by pathology transformation (5.3% vs 4.1%) and MET amplification (5.3% vs 4.1%).
Our results indicated that patients with EGFR exon 19delins mutation presented with significantly better outcomes for first line EGFR-TKI. Dominate resistant mechanism were still for EGFR exon 20T790M but significantly be decreased in uncommon EGFR mutations.
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P1.01-22 - Investigation of Acquired Resistance for EGFR-TKI Plus Bevacizumab as 1st Line Treatment in Patients with EGFR Sensitive Mutant NSCLC (ID 2852)
09:45 - 18:00 | Author(s): Tao Jiang
- Abstract
Background
The progression-free survival (PFS) advantage of EGFR-TKI plus Bevacizumab (A+T) over standard TKI monotherapy (T) in the 1st line treatment of EGFR mutant non-small cell lung cancer (NSCLC) has been confirmed in prospective clinical trials. However, the acquired resistance mechanism which impacts the subsequent management was poorly understood. We did the first analysis to unveil it using next generation sequencing (NGS).
Method
256 EGFR sensitive mutant (EGFR 19del and L858R) NSCLC patients received NGS of 168 genes panel of tumor tissue in baseline from Jan, 2015 to Aug, 2018 was enrolled in this study. 60 patients treated with A+T were recognized as cohort A. Using Propensity Score Matching (Ratio of 1:2), 120 patients treated with single T were chosen as cohort B. Clinical outcomes and resistance mechanism (also by the 168 genes NGS panel) were evaluated.
Result
Newly present alterations in cohort A % N EGFR amp 3.2% 1 MET amp 3.2% 1 MET amp+EGFR amp+TP53 3.2% 1 RB1 3.2% 1 RB1+TP53 3.2% 1 RB1+TP53+EGFR amp 3.2% 1 SMAD4 3.2% 1 T790M 22.6% 7 T790M+BRAF V600E 3.2% 1 T790M+EGFR exon 18 p.V834L+TP53 3.2% 1 T790M+TP53 6.5% 2 TP 53 16.1% 5 unknown 25.8% 8 Total 1 31 Newly present alterations in cohort B % N EGFR amp 6.8% 7 EGFR exon 7 p.T263P 1.0% 1 EGFR exon18 p.G724S 1.0% 1 ERBB2 amp 1.0% 1 KRAS 1.0% 1 MET amp 4.9% 5 MET skipping 1.0% 1 RET+KRAS 1.0% 1 SCLC 2.9% 3 T790M 37.9% 39 T790M+BRAF V600E 1.0% 1 T790M+EGFR amp 8.7% 9 T790M+MET amp 1.9% 2 T790M+TP53 1.9% 2 TP53 4.9% 5 TP53+RB1 1.0% 1 unknown 22.3% 23 Total 1 103 There was no different for clinical characteristics between Cohort A and B. Comparing with single T, A+T significantly prolonged the medium PFS (16.5m vs.12.0m, HR=0.7, p=0.001). A+T significantly increased the overall response rate (95% vs 74.2%, p<0.05). Until Jan 2019, 31 patients in cohort A, 103 patients in cohort B were evaluated with progressed disease and received tissue re-biopsy for NGS with the same 168 genes panel. In cohort B, T790M was defined as the domain acquired resistance mechanism, contributing to 51.5% (53/103) of progressed patients, followed by EGFR amplification 15.5% (16/103), MET amplification 6.8% (7/103), TP53 mutations 6.8% (7/103) and small cell lung cancer transformation 2.9% (3/103). However, in cohort A, although T790M was also defined as the domain acquired resistance mechanism, the mutation ratio was decreased to 35.5% (11/31), followed by TP53 mutations 29.0% (9/31), RB1 mutations 9.7% (3/31), EGFR amplification 9.7% (3/31), MET amplification 6.5% (2/31), and novel SMAD4 mutations 3.2% (1/31), EGFR uncommon mutation (p.V834L) 3.2% (1/31).
Conclusion
Treatment of 1st line A+T significantly extends the time to progression and increases the response rate with acceptable safety profile. The dominant acquired resistance mechanism retained in T790M but with lower probability. SMAD4 mutation and EGFR p.V834L were considered as novel resistant mechanism to A+T.
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P1.04 - Immuno-oncology (ID 164)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 2
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.04-46 - PD-1 Inhibitor Plus Chemotherapy as 2nd/Subsequent Line Setting Demonstrate Superior Efficacy Over PD-1 Inhibitor Alone in Pts of Advanced NSCLC (ID 2878)
09:45 - 18:00 | Author(s): Tao Jiang
- Abstract
Background
PD-1/PD-L1 inhibitors have become standard of care as the 2nd-line setting and also approved as 1st line setting when combined with doublet chemotherapy in patients with advanced NSCLC. This study aims to compare the efficacy of PD-1 inhibitor plus chemotherapy with PD-1 inhibitor alone as 2nd/subsequent lines setting in patients with advanced NSCLC
Method
Patients who received PD-1 inhibitor monotherapy or PD-1 inhibitor plus chemotherapy as 2nd/subsequent lines setting in Shanghai Pulmonary Hospital, Tongji University were retrospectively collected. Detailed clinicopathologic characteristics and therapeutic outcomes were analysis.
Result
From January 2016 to February 2019, 148 patients who meet the criteria were included. Among them, 116 were in PD-1 inhibitor monotherapy group and 32 were in PD-1 inhibitor plus chemotherapy group. Chemotherapy regimens were pemetrexed(n=9), docetaxel(n=2), nab-paclitaxel(n=18) and gemcitabine(n=3). The baseline characteristics such as age, gender, smoking status, histology, PD-1 mono-antibodies, line of therapy were similar in the 2 groups. Combination group showed a favorable ORR (28.1% vs. 13.8%, p=0.055) and a significantly longer PFS(median 4.9 vs 2.5 months, p=0.005) compared with ICI monotherapy. Overall survial (OS) data was immature in the cutoff date of follow up. In the subgroup of 96 patients (monotherapy group n=69/ Combination group n=27) who were included as 2nd line setting, PD-1 inhibitor plus chemotherapy had significantly higher ORR(ORR:33.3% vs 18.8%, p=0.129) and longer PFS(median PFS: 4.9 vs 2.9 months, p=0.041).
Conclusion
PD-1 inhibitor plus chemotherapy as 2nd/subsequent lines setting demonstrated superior efficacy over PD-1 inhibitor alone in patients with advanced NSCLC.
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P1.04-57 - Metronomic Dosing of Chemotherapy Alters Antitumor Immunity and Synergizes with PD-1/PD-L1 Inhibition in Non-Small Cell Lung Cancer (Now Available) (ID 1216)
09:45 - 18:00 | Author(s): Tao Jiang
- Abstract
Background
The combination of immune checkpoint blockade with chemotherapy is currently under investigation as a promising strategy for the treatment of non-small cell lung cancer. Although it has been reported that metronomic dosing of cisplatin can be immune stimulating, the impact of its combination with anti-PD-1/PD-L1 immunotherapy for the treatment of lung cancer remains to be evaluated. Therefore, the current study aimed to explore whether combining low-dose continuous chemotherapy and anti-PD-L1 treatment can induce synergistic antitumor effect by enhancing antitumor immune response in murine lung cancer.
Method
We evaluated the antitumor effects of conventional dose of cisplatin and low-dose metronomic dose of cisplatin as monotherapy or in combination with anti-PD-L1 monoclonal antibody in a murine lung cancer model using Lewis lung cancer cells (LLC). And the changes of immune components in tumor were tested in different treatment groups by flow cytometry and immunohistochemistry.
Result
The results showed that low-dose metronomic use of cisplatin could eradicate Foxp3+ regulatory T cells (Tregs) and myeloid derived suppressive cells (MDSCs). Furthermore, combining low-dose cisplatin and anti-PD-L1 therapy could not only increase the inflitration of CD8+ T cells ,especially IFN-γ+CD8+ T cells , but also significantly reduce the expression of PD-1 and PD-L1. In a syngeneic mouse model of NSCLC, we observed that concurrent use of low-dose cisplatin and anti–PD-L1 delayed tumor growth and enhanced survival.
Conclusion
Low-dose continuous cisplatin treatment can modify tumor immune microenvironment by eliminating immunosuppressive components like Tregs and MDSCs and enhance antitumor immune response, which can be enhanced by PD-1/PD-L1 blockade and therefore induced a synergistic anti-tumor effect.
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P2.14 - Targeted Therapy (ID 183)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.14-51 - Dual ALK Fusion Partners as Poor Predictive Marker in First Line Crizotinib Treated ALK Rearranged Non-Small Cell Lung Cancer (ID 2971)
10:15 - 18:15 | Author(s): Tao Jiang
- Abstract
Background
First line crizotinib response duration time differs with different fusion patterns in ALK-rearranged advanced non-small cell lung cancer (NSCLC) patients. Some former researches have elucidate the impact of EML4-ALK variants on crizotinib efficacy, however, there was little data about the efficacy of crizotinib considering different fusion partners including one patient with two or more fusion partners or non-EML4 partners.
Method
150 patients with NGS-identified ALK-rearranged NSCLC from March 2014 to July 2018 in Hunan Cancer Hospital were enrolled in this study. Among them, 112 patients received crizotinib as first-line treatment. Efficacy of crizotinib was evaluated and categorized according to different fusion partners.
Result
Among 150 advanced NSCLC patients with NGS-identified ALK-rearranged, 181 fusion partners were detected including 43 novel fusion partners. 122 patients (81.3%) were identified with single ALK fusion partners, 28 patients (18.7%) were identified with dual or triple ALK fusion partner patients. Among 112 patients received first line crizotinib treatment, 89 patients were identified with single fusion partner (79 for EML4, 10 for non-EML4). 23 patients were identified with dual fusion partner (20 patients with dual fusion partners, 3 patients with triple fusion partners). The overall response rate (ORR) was 85.2% and the median progression-free survival time (mPFS) was 11.7 months. The frequency of brain metastasis was high in dual fusion partner patients. Patients with dual ALK fusion partners have a significantly shorter mPFS compared with patients carrying single ALK fusion partner (6.1m vs. 12.0m, p=0.001). Patients with EML4 partners have a significantly longer mPFS compared with patients carrying non-EML4 fusion partners (12.6m vs. 6.1m, p=0.004).
Fusion partners EML4-ALK fusion variants Number of patient Percentage of patient(%) C9orf3-ALK 2 1.3% CLIP1-ALK 1 0.7% CYBRD1-ALK 1 0.7% DEFA5-ALK 1 0.7% EML4-ALK V1 31 20.7% EML4-ALK V2 10 6.7% EML4-ALK V3 47 31.3% EML4-ALK V5 11 7.3% EML4-ALK V7 3 2.0% EML4-ALK E3:A20 1 0.7% EML4-ALK E7:A20 1 0.7% EML4-ALK，APOB-ALKE V5 1 0.7% EML4-ALK,ATXN1-ALK V7 1 0.7% EML4-ALK，BIRC6-AS2-ALK V3 1 0.7% EML4-ALK,C1QC-ALK V3 2 1.3% EML4-ALK,COL22A1-ALK V3 1 0.7% EML4-ALK,COL22A1-ALK V1 1 0.7% EML4-ALK,DIRC3-AS1-ALK,CDC42EP3-ALK V3 1 0.7% EML4-ALK,EHBP1-ALK V3 1 0.7% EML4-ALK,FLJ14082-ALK V3 1 0.7% EML4-ALK,LBH-ALK V1 1 0.7% EML4-ALK,LINC00486-ALK V3 1 0.7% EML4-ALK,LINC01121-ALK V1 1 0.7% EML4-ALK,LOC102467222-ALK V3 1 0.7% EML4-ALK,LOC388942-ALK V1 1 0.7% EML4-ALK,LOC388942-ALK, V3 1 0.7% EML4-ALK,LRRTM4-ALK V3 1 0.7% EML4-ALK,MBOAT2-ALK V2 1 0.7% EML4-ALK,MTA3-ALK,SP3-ALK V1 1 0.7% EML4-ALK,MYH7-ALK V2 1 0.7% EML4-ALK,PDE6D-ALK V1 1 0.7% EML4-ALK,QPCT-ALK V1 1 0.7% EML4-ALK,RC3H2-ALK V1 1 0.7% EML4-ALK,SGPP2-ALK V3 1 0.7% EML4-ALK,SIX3-AS1-ALK V2 1 0.7% EML4-ALK,SRBD1-ALK V3 1 0.7% EML4-ALK,THADA-ALK V3 1 0.7% EML4-ALK,TSPYL6-ALK,ABCG8-ALK V3 1 0.7% FAM179A-ALK 1 0.7% GBE1-ALK 1 0.7% KLC1-ALK 1 0.7% LOC388942-ALK 1 0.7% NCOA1-ALK 1 0.7% RP11-433C9.2-ALK 1 0.7% RPSA-ALK 1 0.7% SLC8A1-ALK 1 0.7% STRN-ALK 1 0.7% THADA-ALK 1 0.7% UBXN2A-ALK 1 0.7% USP34-ALK 1 0.7% WDR37-ALK 1 0.7%
Conclusion
Efficacy of first-line crizotinib in ALK-rearranged NSCLC patients differs based on different ALK fusion partners. Dual ALK fusion partners were poor prognostic factors in first-line crizotinib treatment NSCLC. It also correlated with more brain metastasis compared with single fusion partners.
