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Yutao Liu
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P1.12 - Small Cell Lung Cancer/NET (Not CME Accredited Session) (ID 944)
- 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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P1.12-03 - A Prospective Study of Apatinib in Advanced Small Cell Lung Cancer Patients Failed from Two or More Lines of Chemotherapy (ID 13140)
16:45 - 18:00 | Presenting Author(s): Yutao Liu
- Abstract
Background
Small lung cancer (SCLC), a highly malignant neoplastic, chemoresponsive disease. For SCLC patients who with worsening status after second-line treatment, there is currently no affirmative and widely accepted chemotherapy regimen. Apatinib is a novel oral multi-target small-molecule TKI mainly targeting the intracellular ATP-binding domain of VEGFR-2, which has a significant effect of anti-angiogenesis to suppress the growth of tumors. This study evaluated the efficacy and safety of Apatinib in SCLC patients who failed from second- or further-line chemotherapy.
a9ded1e5ce5d75814730bb4caaf49419 Method
Data was collected from the files of patients treated with Apatinib 500mg qd who diagnosed with advanced SCLC and failed from second or more lines of chemotherapy. Efficacy assessed after one cycles (4 weeks), then every two cycles (8 weeks) once again. The primary endpoint was PFS and the tumor response was determined according to the RECIST 1.1. PFS were graphed by Kaplan-Meier curves of progression-free survival. AEs were also evaluated and toxicity grade was determined based on CTCAE 4.0.
4c3880bb027f159e801041b1021e88e8 Result
22 patients were enrolled from November 10, 2016 to April 18, 2018, the number of patients that can be evaluated is 19. One patients obtained partial response, and 15 obtained stable disease, representing a DCR of 84.11%. Median PFS was 140 days (95% confidence interval [CI] 94.84–185.16). Although only one patient showed PR, all the patients’ target lesions were reduced. A total of 46 AEs were reported during the trial, grade 3-4 AEs were hypertension (9.09%), leukopenia (4.55%) and proteinuria (4.55%) which most could be relieved by dose reduction.
8eea62084ca7e541d918e823422bd82e Conclusion
In conclusion, Apatinib has a certain therapeutic effect in patients with advanced SCLC (third- or further-line). To further investigate the role of Apatinib in advanced SCLC patients, large sample and additional clinical trials are needed.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)
- 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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P1.13-18 - Exploring the Resistance Mechanism of Osimertinib and Monitoring the Treatment Response Using Plasma ctDNA in Chinese NSCLC Patients (ID 13297)
16:45 - 18:00 | Author(s): Yutao Liu
- Abstract
Background
Osimertinib (AZD9291; Tagrisso) is a third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) known to be effective for patients harboring the EGFR-T790M variant, which is accounts for more than half of the acquired resistance mechanisms to the first generation EGFR-TKIs. However, limited osimertinib resistance-mechanism was reported. Study on potential osimertinib-resistance mechanisms in advanced NSCLC is necessary.
a9ded1e5ce5d75814730bb4caaf49419 Method
This study enrolled eight T790M-positive (tissue validated) patients, treated with osimertinib after first generation EGFR-TKI (Erlotinib, Gefitinib, Icotinib) resistance and progressed rapidly. Serial plasma samples were collected until disease progressed. Plasma DNA was extracted and sequenced by target-capture deep sequencing of 1021 previously annotated genes related to solid tumors. Clonal EGFR T790M mutation was defined if mutation was in the cluster with the highest mean variated allele frequency with PyClone, and otherwise subclonal EGFR T790M mutation. Molecular tumor burden index (mTBI) was calculated with the mean variant allele frequency of mutations in trunk clonal population.
4c3880bb027f159e801041b1021e88e8 Result
The median progression-free survival (PFS) of these eight rapidly-progressed patients was 3.82 months [95% CI 2.05-5.01] .Targeted capture sequencing of pretreatment ctDNA showed all of the eight patients (100%) were EGFR-positive (Exon19del [n=6] and L858R [n=2]), and seven patients (88%) harbored EGFR T790M mutation, except for the only one patient (P006) who showed an extremely low level of ctDNA. During the Osimertinib treatment, five patients (63%) had osimertinib resistance-related mutations: EGFR C797S (in cis position), G724S, KRAS G12D, PIK3CA E542K, EGFR amplification, and ERBB2 amplification. Among them, two patients had more than one resistance mechanisms: patient P034 had EGFR G724S, KRAS G12D and EGFR amplification, simultaneously; patient P013 had amplification in both EGFR and ERBB2. Other potential resistance mechanisms were identified including EGFR T751I and K754E mutations in P002 and ERBB2 S603 in P013. Notably, the only one patient (P004) who had not been detected to have any known osimertinib resistance mechanism but progressed in 3 months, was demonstrated to harbor a subclonal EGFR T790M mutation by analysis of ctDNA clonal structure. Serial ctDNA monitoring showed mTBI increased when disease progressed in 88% (7/8) patients, except P006, whose mutation were negative at second (stable disease) and third (progressed disease) therapeutic evaluations due to the extremely low level of ctDNA.
8eea62084ca7e541d918e823422bd82e Conclusion
This study presented comprehensive the resistance mechanism of osimertinib progressed rapidly in ctDNA including multiple mechanisms co-occurred in same patient. Serial monitoring of plasma ctDNA may be a promising approach to explore resistance mechanism and monitored the treatment response of third generation EGFR-TKI.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.01-44 - Prognostic Value of TP53 Hot Exon Mutation in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) (ID 13150)
16:45 - 18:00 | Author(s): Yutao Liu
- Abstract
Background
Numerous studies have revealed either very marginal or no prognostic value of TP53 mutation NSCLC patients. Currently, in clinical settings, all TP53 mutations have been considered equally, without any differentiation between the various types and positions of mutations. However, increasing evidence has triggered us to challenge such practice.
a9ded1e5ce5d75814730bb4caaf49419 Method
We retrospectively investigated the correlation between mutations occurring at hot exons (5-8) and overall survival (OS) in 214 previously tyrosine kinase inhibitor (TKI) treated advanced NSCLC patients. Among them, 184 had 1 line of TKI-treatment and the remaining 30 patients had more than 1 line of TKI-treatment. 115 harbored TP53 mutation; among them 105 patients had concurrent EGFR mutation; 5 had ALK rearrangements; 1 had ROS1 rearrangements; 1 had KRAS and 2 had ERBB2 mutations. 99 patients had wild type (WT) TP53; among them, 92 had EGFR mutation, 4 with ALK-rearrangements, 1 with MET and 1 with BRAF mutation. Fisher’s exact test and the Mann-Whitney test were used to determine if categorical and continuous variables, respectively, differed between TP53 WT and mutant groups.
4c3880bb027f159e801041b1021e88e8 Result
The prevalence of TP53 mutation in our cohort is 53.7% (115/214); 28 had mutation on exon 5, 18 on exon 6, 22 on exon 7 and 32 on exon 8. 32 patients had loss of function mutation and 51 patients had disruptive mutation. Our data revealed a positive correlation with N and M stage. Patients harboring TP53 mutation are more likely to diagnose with more advanced N (p=0.018) and M stage (p=0.001). Furthermore, patients with TP53 mutation are more likely to have liver (p<0.001) and bone metastasis (p=0.012). In patients treated with only 1 line of TKI-treatment, although TP53 status had no effect on PFS (p=0.241) and OS (p=0.49) when they were considered collectively, we observed patients with mutation in exon 5 had shorter OS (p=0.029) and mutation in exon 8 had shorter PFS (P=0.003) after controlling for age, gender, stage and histology. Furthermore, within the osimertinib subgroup (N=101), patients harboring mutation in exon 8 had significantly shorter PFS (P=0.007). In patients treated with more than 1 line of treatment, neither TP53 mutation considered collectively, nor hot exon mutations had correlation with PFS or OS.
8eea62084ca7e541d918e823422bd82e Conclusion
Our study revealed unfavorable prognostic value of mutations in exon 5 and no prognostic value of TP53 if all mutations were considered collectively. Our study adds new dimension to the emerging picture that not all TP53 mutants are equal.
6f8b794f3246b0c1e1780bb4d4d5dc53
