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Shengxiang Ren
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P1.03 - Chemotherapy/Targeted Therapy (ID 689)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 2
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.03-045 - HER-2 Mutation Is Not a Prognostic Factor Treated with First-Line Chemotherapy in NSCLC Patients (ID 10386)
09:30 - 16:00 | Author(s): Shengxiang Ren
- Abstract
Background:
Human epidermal growth fator2 (HER-2) is a driver gene in non-small cell lung cancer (NSCLC), however, the effect of chemotherapy in patients with HER-2 mutation has not been studied.
Method:
HER-2 mutation was detected in 1041 EGFR/ALK/ROS1/KRAS/BRAF wild type NSCLC patient samples in Shanghai Pulmonary Hospital using ARMS method, and the mutation positive samples were confirmed by DNA sequencing. The clinicopathologic features and prognosis of the HER-2 mutation patients were analyzed.
Result:
63 samples (6.1%) were HER-2 mutation positive, and 53 samples (84.1%) were confirmed by DNA sequencing. 5(7.9%) were point mutation and 58(92.1%) were insertion mutations with 33 (52.4%) A775_G776insYVMA. Patients with A775_G776insYVMA mutation had no association with other mutations in sex, age, smoking status, and pathological types, as well as in objective response rate (ORR, 40.0% vs 28.6%, p=1.000) and progression-free survival (PFS, p=0.069). Patients with six gene wild type were matched with the 63 HER-2 mutation patients in clinicopathologic features. We found that there was no significant difference between HER-2 mutation and wild type patients in ORR (30.4% vs 29.3%, p=0.157) and PFS (7.0month vs 4.5month, p=0.086), although the PFS was longer in HER-2 mutation patients.
Conclusion:
HER-2 mutation was 6.1% in EGFR/ALK/ROS1/KRAS/BRAF wild type NSCLC patients. There was no significant difference between HER-2 mutation and wild type patients in ORR and PFS treated with first-line chemotherapy. Target therapy maybe needed to treat these patients.
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P1.03-052 - Comparing EGFR-TKI with EGFR-TKI plus Chemotherapy as 1st Line Treatment in Advanced NSCLC Patients with Both Mutated EGFR and Bim Polymorphism (ID 10516)
09:30 - 16:00 | Author(s): Shengxiang Ren
- Abstract
Background:
Not all advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) activating mutations could get benefit from 1[st] line treatment of EGFR tyrosine kinase inhibitors (TKIs). Our previous study indicated that B-cell chronic lymphocytic leukemia/lymphoma-like 11 (Bim) deletion polymorphism was about 10% and was significantly associated with a poor clinical response to EGFR-TKIs in EGFR mutation-positive NSCLC. This retrospective study compared efficacy and tolerability of the EGFR-TKI alone versus EGFR-TKI plus chemotherapy as the 1[st] line treatment in advanced NSCLC patients with both activated EGFR mutation and Bim polymorphism.
Method:
Main included criterias were patients older than 18 years, histologically confirmed stage IIIB or IV NSCLC, EGFR mutation-positive (exon 19 deletion or 21 L858R mutation) and Bim polymorphism. Patients received gefitinib 250mg orally a day or gefitinib together with up to 4 cycles of pemetrexed/gemcitabine and platinum until disease progression or unacceptable toxic effects. The primary endpoint was progression-free survival (PFS); the second endpoint included objective response rate (ORR), overall survival (OS) and toxicity.
Result:
From June 2014 to September 2016, 65 patients were enrolled into this trial. 36 of them received gefitinib, and 29 received gefitinib plus pemetrexed/gemcitabine and platinum. Median PFS was significantly longer in EGFR-TKI plus chemotherapy-treated patients than in EGFR-TKI (7.2 [95% CI 5.35-9.05] vs 4.6 [4.01-5.19] months; p=0.008). The ORR was significantly lower in EGFR-TKI than in EGFR-TKI plus chemotherapy-treated patients (38.9% vs. 65.5% p=0.046). EGFR-TKI plus chemotherapy was associated with more grade 3 or 4 hematological toxic effects than EGFR-TKI (8 neutropenia, 4 thrombocytopenia vs. no any event). Figure 1
Conclusion:
Compared with EGFR-TKI, EGFR-TKI plus chemotherapy conferred a significant higher ORR and longer PFS in advanced NSCLC patients with both activated EGFR mutation and Bim polymorphism. An open-label, multicenter, randomized, phase 2 study is ongoing to validate these results in our institute ( NCT03002844).
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P1.15 - SCLC/Neuroendocrine Tumors (ID 701)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.15-009 - Safety and Efficacy of Nab-Paclitaxel Monotherapy as 2nd or Later Line Setting in Pts with Extensive SCLC, a Phase II Single Arm Study (NCT02262897) (ID 9583)
09:30 - 16:00 | Presenting Author(s): Shengxiang Ren
- Abstract
Background:
There is still an unmet need for patients with extensive small cell lung cancer(SCLC) who failed from the previous treatment even though topotecan was approved by Food and Drug Administration as second line setting in this population. Nab-paclitaxel (nab-P) has showed promising efficacy in pancreas cancer, breast cancer and nonsmall cell lung cancer, this phase II trial try to evaluate the safety and efficacy of nab-paclitaxel (nab-P) monotherapy as the secondary or later line therapy in patients with extensive SCLC.
Method:
Main included criteria were performance status 0-2, extensive disease, failed or insensitive relapse from the previous treatment, sufficient myeloid function. Sensitive relapsed from the last line chemotherapy was excluded. Patients who met these criteria received weekly nab-paclitaxel 130mg/m2, d1,8,15, every 4 week or nab-paclitaxel of 230 mg/m2, d1 every 3 weeks. The Primary end point is objective response rate. The secondary end point included progression free survival(PFS), overall survival, and side effects.
Result:
From Sep, 2014 to Mar, 2017, 40 patients were included into this study, included 39 males, 6 never smokers, PS 1/2:27/13 with a median age of 66 years. The median line of nab-P monotherapy is 3(2-5). Among them, 30 patients received weekly nab-P and 10 received nab-P every 3 weeks. 9, 27, 4 patients were resistant, refractory and sensitive relapse to first line chemotherapy respectively. 7 patients got partial response,17 stable diseases and 16 progression disease. The objective response rate was 17.5% and disease control rate(DCR) was 60%. The median PFS was 3 months and the during of response was 5.8 months. Subgroup analysis showed that patients who were refractory or sensitive relapse to first line chemotherapy had a significant higher DCR (67.8% vs 28.5%, p=0.042) and longer PFS(3.3 vs 1.4 months, p=0.04), while similar results were found in different PS, smoking status and lines of therapy. Toxicity was mild and manageable including alopecia, neuritis, neutropenia and anemia, no grade 3/4 adverse event observed.
Conclusion:
Nab-P showed promising efficacy together with acceptable toxicity in patients with extensive SCLC who failed or insensitive relapse from the previous treatment, especially in the subgroup of refractory or sensitive relapse to first line chemotherapy, large cohort study is needed to validate these findings.
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P2.07 - Immunology and Immunotherapy (ID 708)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.07-047 - Poor Performance Status and BRAF Mutation Predict Grade 3-5 Immune-Related Adverse Events in Pts with Advanced NSCLC (ID 10175)
09:30 - 16:00 | Author(s): Shengxiang Ren
- Abstract
Background:
Anti-PD1/PDL1 immunotherapy has been regarding as standard second line therapy in patients with advanced NSCLC, also as the 1[st] line setting in subpopulation with PDL1 expression of more than 50%. Anti-PD1/PDL1 drugs such as nivolumab, pembrolizumab and atezolizumab showed a durable response in those benefit population, while immune-related adverse events(irAEs) were also frequently happened. This study aimed to describe the high-risk factors for irAEs in patients with advanced NSCLC after the treatment of anti-PD1/PDL1 monoclonal antibody.
Method:
We retrospectively reviewed 72 patients with advanced non small cell lung cancers treated with PD-1/PD-L1 inhibitors (nivolumab =27, pembrolizumab =44, atezolizumab =1) in Shanghai Pulmonary Hospital from Jun 2015 to May 2017. All adverse events were assessed and classified by grades according to NCI CTCAE (version 4.0).
Result:
AEs occurred in 34 patients (47.22%). Grade 1 or 2 events included increased amylase (5), increased lipase (5), transaminitis (4), rash/ pruritus (4), xerostomia (3), nausea (3), fatigue(3), anemia (3), decreased WBC (2), hypokalemia (2) and fever, arthralgia, sense of neck stiffness, cardiac arrhythmia, decreased PLT and hypocalcemia in 1 patient each.Twelve (16.67%) patients experienced grades 3-5 events including 6 cases with ILD(grade 5=1), 3 with pleural effusions/pericardial effusions, 2 with hypothyroidism, and 1 with grade 3 fatigue. Subgroup analysis showed that patients with BRAF mutations(2 with adenocarcinomas,1 with squamous carcinomas and 1 with NSCLC) experienced significantly higher rate of serious AEs (2 ILD and 2 pleural effusions) after receiving pembrolizumab (100%vs 11.76%,p＜0.001), while it was similar according to the other driver genes mutation status (EGFR, KRAS, HER2, ALK). Patients with poor ECOG PS experienced a marginally statistically significant higher grade 3-5 AEs (p=0.063), while it was similar according to different subgroup of age (p=0.538), gender (p=0.189), histological type (p = 0.999), smoking status (0.122), lines of previous therapy (p=0.172), baseline serum LDH level(p=0.290) and CD8+ of peripheral blood (p=0.814). In addition, prior thoracic radiation has a numerical higher prone to develop ILD (23.07%vs 5.08%, p = 0.116).
Conclusion:
Poor performance status and BRAF mutation might predict irAEs in patients with advanced NSCLC receiving PD-1/PD-L1 inhibitors, further large cohort study is warranted to investigate the high-risk factors for irAEs in patients with advanced NSCLC.
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-067 - TP53 Mutations Could Involved in EGFR-TKI Primary Resistance in Advanced Non-Small Cell Lung Cancer (ID 10437)
09:30 - 16:00 | Author(s): Shengxiang Ren
- Abstract
Background:
Activating mutations in the epidermal growth factor receptor (EGFR) are strongly predictive of EGFR-tyrosine kinase inhibitor (TKI) activity in non-small cell lung cancer (NSCLC). However, primary resistance to EGFR-TKIs occurs in approximately 20-30% of NSCLC patients with EGFR mutations, acquired resistance is inevitable. The aim of study is to discover unknown resistant mechanisms and contribute to more precisely administrate advanced and metastatic NSCLC with EGFR mutations.
Method:
60 NSCLC patients with EGFR sensitive mutation were enrolled this study. All of patients received EGFR-TKI treatment. 21 of patients were primary resistance and 39 acquired resistance according to Jackman standard. Tumor tissues of all of patients were collected before EGFR-TKIs treatment, and rebiopsy tissues were gained after acquired resistance in 39 NSCLC patients. Whole exome sequencing were performed in Illumina HiSeq2000 platform. The captured sequencing data was further processed to identify somatic mutations, including single nucleotide variants (SNVs), short insertions/deletions (indels) and copy number variations (CNVs).
Result:
In primary resistance patients, 13 patients occurred rapid progress (PFS ≤60 days) were put into group 1, and other 8 patients with PFS within 90-180 days were into group 2; in acquired resistance patients, 9 patients were observed long-term clinical benefit (PFS≥540 days) were into group 3; remaining 30 patients with PFS between 180 to 540 days were into group 4. Median PFS were 29, 95, 761 and 311 days from group 1 to 4, respectively. More signaling pathways were activated in group 1, relative to other groups, including bypass activation, downstream signal activation, apoptotic pathways disturbance and EMT activation. Meanwhile, the activation of more signaling pathways were found in samples after acquired resistance compared with paired baseline samples. In all of baseline samples, 60.0% patients harbored TP53 mutations, and these mutations distributed in exon 2,4,5,6,7,8 and 11, respectively. Interestingly, TP53 mutations of 23% patients were in exon 6 in group 1, mutations in exon 5 occurred in 33.3% patients with long-term clinical benefit (group 3). Patients with exon 6 mutation had more shorter PFS than those with exon 5 mutation (105 days vs 284 days).
Conclusion:
For patients resistant to EGFR-TKI, more signal pathways were activation, and the heterogeneity of tumor cloning were complicated. TP53 mutations in different exons may have distinct effect on response to EGFR-TKI of patients with EGFR sensitive mutation.
