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Chunxia Su
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MA15 - Colliding Approaches - EGFR and Immunotherapy (ID 916)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 13:30 - 15:00, Room 107
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MA15.10 - Loss of T790M Mutation is Associated with Early Progression to Osimertinib in Chinese Advanced NSCLC Patients Harboring EGFR T790M (ID 13645)
14:35 - 14:40 | Author(s): Chunxia Su
- Abstract
- Presentation
Background
Osimertinib has demonstrated striking superior efficacy in non-small cell lung cancer (NSCLC) patients detected acuqired T790M mutation as resistant mechanism to upfront early-generation EGFR-TKIs. However, not all the T790M positive tumors are homogeneously sensitive to osimertinib, and the duration of response often varies. Previous studies suggest that loss of T790M mutation upon progression is related to decreased therapeutic benefit from osimertinib. The aim of this study is to investigate the association of T790M-mutant status and clinical outcomes after osimertinib treatment in Chinese NSCLC patients harboring acquired EGFR T790M mutation.
a9ded1e5ce5d75814730bb4caaf49419 Method
We reviewed the electric medical records of all patients receiving osimertinib monotherapy after detected acquired T790M mutation in rebiopsy after resistant to prior EGFR-TKIs, and underwent re-rebiopsy again upon progression to osimertinib at our hospital. Detailed clinicopathologic characteristics and response data were collected for all patients.
4c3880bb027f159e801041b1021e88e8 Result
From January 2014 to December 2016, 230 patients were confirmed T790M mutation positive for acquired resistance to early-generation EGFR-TKIs (gefitinib, erlotinib, afatinib and icotinib). Among them, 90 patients received osimertinib monotherapy as subsequent treatment. Out of the patients, 84 (93.3%) were eligible for osimertinib-resistance analysis, and 31 (34.4%) patients underwent T790M detection in biopsy after disease progression to osimertinib. The most commonly used biopsy sample were tumor tissue, peripheral blood and hydrothorax. 16 patients remained T790M positive, while 15 patients lost T790M mutation in their re-rebiopsy samples. Loss of T790M upon progression was significantly associated with shorter duration of response to osimertinib (median time 5.93 vs 11.87 m, HR:0.325, 95%CI: 0.087 to 0.45, p=0.0005), while overall survival (OS) was not statistically different between T790M-loss and -remain groups. The objective response rates were also similar in two groups (85% and 100%, respectively). In multivariate analysis, T790M mutation loss remained significantly associated with early progression to osimertinib.
8eea62084ca7e541d918e823422bd82e Conclusion
Loss of T790M mutation was associated early progression to osimertinib in Chinese NSCLC patients harboring acquired T790M mutation. Dynamic detection during osimertinib treatment may be a potential strategy to timely reveal disease progression.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MA26 - New Therapies and Emerging Data in ALK, EGFR and ROS1 (ID 930)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 13:30 - 15:00, Room 201 BD
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MA26.05 - Comprehensive Analysis of Treatment Response and Progression Pattern in Chinese Patients with Different ALK Fusion-Variants (ID 13883)
14:00 - 14:05 | Author(s): Chunxia Su
- Abstract
- Presentation
Background
ALK inhibitors and chemotherapy are two major strategies in the treatment of patients with ALK-rearrangements in China. However, the respective treatment response varies and heterogeneous. This study aimed to comprehensively analyze the impact of ALK variants on different treatment response and explore progression pattern respectively.
a9ded1e5ce5d75814730bb4caaf49419 Method
We retrospectively analyzed a cohort of 135 patients with determined ALK variants and medical record from January 2013 to July 2017 in Shanghai Pulmonary Hospital.
4c3880bb027f159e801041b1021e88e8 Result
8eea62084ca7e541d918e823422bd82e Conclusion
The most frequent ALK variant was variant 1 in 62 patients (46%), followed by variant 3a/b in 52 patients (38%) and variant 2 (12%). 69 (51.1%) of patients received chemotherapy, whereas 64 (47.4%) were treated with crizotinib and 2 (1.5%) with alectinib.The similar PFS was observed in patients ALK variant 1 and non-variant 1 regardless of first-line treatment strategy (crizotinib: 15.7 vs. 12.8 months, p=0.53; chemotherapy: 5.7 vs. 8.1 months, p=0.098). However, in the subgroup analysis, patients with ALK variant 1 and baseline brain metastasis had significantly shorter PFS in the first-line setting versus non-variant 1 (4.9 vs. 11.3 months, HR=2.96, p<0.01). Additionally, ORR was 21.6% and 50% in variant 1 and non-variant 1 patients with brain metastases, respectively. Moreover, in the analysis of progression pattern, 55 patients with ALK variant 1 and 57 patients with ALK non-variant 1 exhibited PD. As to ALK variant 1, the incidence of CNS relapse in patients treated with crizotinib was significantly higher than patients treated with chemotherapy (39.3% vs. 7.4%, p=0.005). In terms of ALK non-variant 1,the patients treated with chemotherapy had higher incidence of bone progression than patients treated with crizotinib (25% vs. 0%, p=0.021).
Our results firstly indicate the treatment-naïve patients with ALK variant 1 and baseline brain metastasis have inferior response to initial cancer treatment. Different ALK variants have distinct landscape of progression pattern when treated with crizotinib or chemotherapy.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.01-111 - EGFR exon20 Insertion Patients Treated with First-Line Chemotherapy in Non-Small Cell Lung Cancer (ID 14323)
16:45 - 18:00 | Author(s): Chunxia Su
- Abstract
Background
Epidermal growth factor receptor exon20 insertion(EGFR 20-ins) is a low frequency mutation among EGFR mutations, and chemotherapy is a major choice for these patients. The outcomes between different types of EGFR 20-ins and with EGFR sensitive mutation and wild type are not well studied.
a9ded1e5ce5d75814730bb4caaf49419 Method
From Oct 2011 to Feb 2018, EGFR 20-ins was detected using ARMS method. The mutation positive samples were subsequently confirmed by DNA sequencing. Clinicopathological features and outcomes between different kind of EGFR 20-ins patients as well as EGFR 20-ins patients with EGFR sensitive mutation and wild type patients were analyzed.
4c3880bb027f159e801041b1021e88e8 Result
Eighty-four 20-ins patients were detected in this study. Eight were not enough for DNA sequencing, 11 were wild type and 65 were mutation positive. The three major subtypes were: 28 c.2308_2309insCCAGCGTGG, 9 c.2311_2312insGCGTGGACA and 10 c.2319_2320insAACCCCCAC. Of the 45 patients who could access treatment effect in first-line chemotherapy, objective response rate(ORR) was 28.9%(13/45), disease control rate(DCR) was 86.7%(39/45) and median progression-free survival (mPFS) was 5.7 month. There were no significant differences in sex, age, smoking status, pathological types, ORR, DCR and PFS between c.2308_2309insCCAGCGTGG mutation and other 20-ins mutations. We compared the PFS of EGFR sensitive mutation, wild type and 20-ins patients, and found no significant difference(p=0.324).
8eea62084ca7e541d918e823422bd82e Conclusion
EGFR 20-ins is a distinct EGFR mutation. The clinicopathological features and clinical outcome were not significantly different between different EGFR 20-ins subtypes, as well as between EGFR 20-ins, EGFR sensitive mutation and wild type patients. Target drugs for this kind of patients are needed.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P2.15 - Treatment in the Real World - Support, Survivorship, Systems Research (Not CME Accredited Session) (ID 964)
- 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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P2.15-33 - Evaluation of Liquid Biopsies for Molecular Profiling in Patients (pts) with Advanced NSCLC: What Happens After Panel Testing by NGS? (ID 13011)
16:45 - 18:00 | Presenting Author(s): Chunxia Su
- Abstract
Background
Molecular profiling is limited by tumor heterogeneity and access to sufficient tissue for comprehensive analysis. Circulating tumor DNA (ctDNA) is promising as a minimally-invasive liquid biopsy for testing gene alterations and monitoring personalised treatment strategies. Because of its high expense, translation of the sensitive and accurate next generation sequencing (NGS) into routine cancer care has been slow.
a9ded1e5ce5d75814730bb4caaf49419 Method
We retrospectively reviewed 60 advanced NSCLC pts who were performed gene test prior to treatment using tissue by ARMS. Blood collections (10ml K2-EDTA) were performed after disease progression and analysed by NGS using a 10-gene panel (EGFR, KRAS, BRAF, HER2, PIK3CA, ALK, ROS1, RET, MET and TP53). We evaluated the significance of the outcome of panel testing by NGS in guiding the subsequent treatment in clinical practice.
4c3880bb027f159e801041b1021e88e8 Result
Among 60 NSCLC pts, 39 were male, 28 were never-smokers, and 56 were adenocarcinoma. ctDNA profiling detected alterations in 50 pts (83%). TP53 (53%), EGFR (48%) and KRAS (15%) were the most common abnormalities detected. Additionally, MET (8%), ALK (3%), HER2 (3%) and PIK3CA (2%) mutations were detected, respectively. Sensitizing mutations were detected in 22 pts (37%) prior to treatment using tissue by the method of ARMS, including 20 EGFR mutations and 2 ALK fusions, and all pts received tyrosine kinase inhibitor (TKI) as first-line therapy. Among 20 EGFR mutant pts, T790M mutation was detected in 9 pts (45%), KRAS mutation was detected in 4 pts (20%), and TP53 mutation was detected in 12 pts (60%), while MET amplification was found in 1 pt (5%). 1 KRAS mutation and 1 TP53 mutation were detected in 2 ALK –TKI resistant pts, respectively. 28 pts (47%) reported as tissue negative had a positive liquid biopsy, including 4 MET 14 exon skipping mutations, 2 EGFR 19 DEL, 4 EGFR L858R and 1 EGFR L861Q, and 2 EGFR T790M mutations. The mutation abundance is all below 1%, except 2 EGFR 19 DEL and 4 L858R. Ten pts received TKIs; 2 got parcial responses, 5 stable diseases and 3 progressive disease.
8eea62084ca7e541d918e823422bd82e Conclusion
ctDNA can be used as a ‘liquid biopsy’ for molecular profiling of NSCLC pts, and NGS, as a highly sensitive method to detect mutations with low mutation abundance, can provide more chances to pts to receive precise treatment.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P3.04 - Immunooncology (Not CME Accredited Session) (ID 970)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.04-21 - Antibiotics Attenuate the Clinical Benefit of Anti-PD-(L)1 Immunotherapies in Chinese Patients with Advanced Non-Small Cell Lung Cancer (ID 13555)
12:00 - 13:30 | Author(s): Chunxia Su
- Abstract
Background
Immune checkpoint inhibitors (ICIs) targeting PD-(L)1 have shifted the treatment paradigm of advanced non-small cell lung cancer (NSCLC), but responses are often heterogeneous and temporary. Several landmark publications have confirmed the dominant role of gut microbiome in modulating tumor responses to ICIs, suggesting the predictive value of antibiotics (ATB) in patients treated with anti-PD-(L)1 antibody. However, more evidence is needed to comprehensively reveal the association between ATB usage and ICIs therapeutic response in NSCLC, especially in Chinese populations.
a9ded1e5ce5d75814730bb4caaf49419 Method
We retrospectively reviewed the medical records of patients with advanced/metastatic NSCLC received anti-PD-(L)1 based therapies at our hospital. Detailed clinicopathologic characteristics, response data and ATB usage were collected for all patients. The patients receiving ATB within one month around the first administration of ICIs (defined as ATB-treated) were compared to those without (ATB-untreated).
4c3880bb027f159e801041b1021e88e8 Result
109 cases receiving anti-PD-(L)1 based therapies and underwent response evaluation were identified. 65 (59.3%) of them received monotherapy and 44 received combination therapies including anti-PD-(L)1 plus anti-angiogenesis/chemotherapy. 35 (32.1%) patients had been prescribed ATB 60 days before or during the course of ICIs treatment, and 20 (18.3%) were categorized as ATB-treated group. The most commonly administered ATB were β-lactam inhibitors, fluoroquinolones and macrolides. No major statistical differences in baseline clinicopathologic features were observed between ATB-treated and -untreated groups. The objective response rates (ORR) to ICIs in two groups were 65% and 82%, respectively. ATB treatment was significantly associated with shorter progression-free survival (PFS) (median 3.73 vs 9.3 m, p<0.001), and also tended to be associated with primary disease progression (35% vs 18%, p=0.087). The overall survival (OS) (median 31.9 vs 37.6 m, p=0.74) was similar in two groups, but ATB appeared to be related to decreased duration of survival from ICI treatment start to death (median 6.07 vs 26.9 m, p=0.002). In multivariable analysis, ATB treatment was markedly associated with poorer ORR and survival to ICIs after adjusting for prior line treatment setting, ICI regimens, numbers of ICI-related toxicity and clinical characteristics.
8eea62084ca7e541d918e823422bd82e Conclusion
ATB usage was a predictor for decreased clinical benefit from anti-PD-(L)1immunotherapies in Chinese NSCLC patients. More comprehensive understanding of the interaction between gut microbiome and ATB is still in urgent need. Furthermore, modulating ATB-related gut microbiome dysbiosis may enhance response to anti-PD-(L)1 immunotherapies.
6f8b794f3246b0c1e1780bb4d4d5dc53
