Virtual Library
Start Your Search
C. Su
Author of
-
+
MA04 - HER2, P53, KRAS and Other Targets in Advanced NSCLC (ID 380)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
-
+
MA04.03 - Preliminary Results of a Phase II Study about the Efficacy and Safety of Pyrotinib in Patients with HER2 Mutant Advanced NSCLC (ID 6069)
16:12 - 16:18 | Author(s): C. Su
- Abstract
- Presentation
Background:
There is still an unmet need for targeted drugs in non small cell lung cancer (NSCLC) patients with HER2 mutation. Pyrotinib is an oral tyrosine kinase inhibitor targeting both HER-1 and HER-2 receptors. This phase II trial is designed to evaluate the safety and efficacy of pyrotinib in patients with HER2 mutant advanced NSCLC.
Methods:
A single arm prospective phase II trial was undergone to evaluate the efficacy and safety of Pyrotinib in patients with HER2 mutant advanced NSCLC in a single center of Shanghai Pulmonary Hospital, Tongji University(NCT 02535507). Pyrotinib was administrated 320mg or 400mg orally once a day. Next generation sequencing or ARMS was used to identify the patients with HER2 mutation. The primary endpoint was objective response rate and the secondary endpoints were side effect, progression free survival and overall survival.
Results:
From Jul 15 2015 to Jul 21, 2016, 11 patients with her2 mutated advanced NSCLC were enrolled into this study. Among them, the median age was 58 years old, 6 were male, 4 were smoker, ECOG PS 0/1/2 were 5/6 and all of them were adenocarcinoma. None of them received pyrotinib as the first line therapy and the median previous anti-cancer regimen was 2. 9 patients had the details variants of HER2 mutation including 7 with exon 20 776YVMA, 1 with exon 20 770AYVM and 1 with 2326G>ATTT. All of them evaluated the response, including 54.5% with partial response(6/11), 27.3% with stable disease(3/11) and 18.2% with progressive disease(2/11). 1 patient got response to pyrotinib after progressed from afatinib. 5 patients were still on the study and the median PFS was 6.2 months. Side effects were mild including 4 with grade I/II diarrhea, 2 with grade II fatigue, 2 with grade I rash and 1 with dispnea.
Conclusion:
Pyrotinib showed promising results about the ORR and PFS together with mild toxicity in patients with HER2 mutant advanced NSCLC, further multicenter large scale phase II study is initiated to validate the results in this study.
Only 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.
-
+
MA15 - Immunotherapy Prediction (ID 400)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
- Moderators:O. Arrieta
- Coordinates: 12/07/2016, 14:20 - 15:50, Schubert 1
-
+
MA15.03 - The Predictive Value of Mutation/Neoantigen Burden from ctDNA on the Efficacy of PD-1 Blockade in Advanced NSCLC (ID 5884)
14:32 - 14:38 | Author(s): C. Su
- Abstract
Background:
Immune checkpoint, PD-1, inhibitors, have been approved to treat advanced NSCLC patients without oncogenic driver in the second-line setting based on durable clinical benefit. It has been demonstrated that the overall mutational burden in tumor tissue was significantly associated with progression free survival (PFS) of advanced NSCLC patients treated with PD-1 inhibitor. However, tumor tissue may not be available from all patients at any time during PD-1 blockade therapy. Therefore, the purpose of this study was to explore the predictive value of mutation/neoantigen burden from ctDNA on efficacy of PD-1 inhibitors.
Methods:
We treated advanced NSCLC patients without oncogenic drivers with PD-1 inhibitor in the second or more line setting. The whole-exome of tumor tissues and ctDNA at baseline and ctDNA at every time of efficacy evaluation from these patients were sequenced by NGS. The hybrid-capture-enriched libraries were sequenced on the Illumina HiSeq 4000 platform with 75-base paired-end reads, sequencing depth was 300 for ctDNA whole-exome sequencing. We compared the results of whole-exome sequencing between patients who achieved objective response to PD-1 inhibitor and patients who experienced disease progression. Besides, we also compared the results of whole-exome sequencing between baseline ctDNA and ctDNA extracted at efficacy evaluation.
Results:
Up to now, a total of 23 patients treated with PD-1 inhibitor received efficacy evaluation at least once in this study. Of them, 4 patients achieved partial response (PR), 3 patients achieved stable disease (SD). Of 4 patients with PR, 3 patients were found to harbor high mutation burden (more than 400 nonsynonymous mutations) from ctDNA and only 1 patient harbored mutation burden of less than 100 from ctDNA at baseline. We found the mutation or neoantigen burden from ctDNA changed during PD-1 blockade therapy. The efficacy of PD-1 inhibitor appeared to be more significantly associated with neoantigen burden rather than mutation burden. Only one ctDNA sample was found positive for MSH6 mutation (C1337X) and all baseline ctDNA samples were negative for microsatellite instability (MSI) status.
Conclusion:
Evaluating nonsynonymous mutation burden/neoantigen burden from ctDNA was feasible in advanced NSCLC patients treated with PD-1 inhibitors. The predictive value of neoantigen burden from ctDNA on the efficacy of PD-1 inhibitor may be better than that of mutation burden in advanced NSCLC. It may not be feasible to determine the status of mismatch-repair deficiency and MSI using ctDNA samples in advanced NSCLC. An expanded study is ongoing. More details will be presented in the conference.
-
+
P2.03b - Poster Session with Presenters Present (ID 465)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
P2.03b-092 - Predictive and Prognostic Effect of Circulating Tumor Cells in Non-Small Cell Lung Cancer Treated with Targeted Therapy (ID 4815)
14:30 - 14:30 | Author(s): C. Su
- Abstract
Background:
We propose a non-invasive, folate receptor (FR)–based circulating tumor cell (CTC) detection approach to interpret treatment response of targeted therapy between baseline and follow-up CTC values and the feasibility whether CTCs as a prognostic factor in advanced NSCLC with EGFR mutation/ALK translocation.
Methods:
This was a prospective, unopen-labeled, single-center trial. From July 25, 2014 to March 11,2016, 308 advanced NSCLC patients were enrolled to quantified CTC level by negative enrichment using immunomagnetic beads in combination with folate receptor-directed polymerase chain reaction(PCR) that allows secondary amplification of tiny amounts of CTCs in 3mL peripheral blood before the start of targeted therapy and after one month, every two months hereafter of treatment. Among whom, 272 NSCLC patients with EGFR mutation (exon 19Del mutation: n=135, L858R mutation: n=137) ,39 ALK translocation or undefined lung cancer patients. Sequential analyses were conducted to monitor CTC values during therapy and correlate radiological effects with treatment outcome.
Results:
There was no significant difference between CTC values and patients’ characristics including stage (P= 0.1015), EGFR mutation status(19 del:14.5 CTCs, L858R:12.6 CTCs, P=0.1868) , age (≤60 versus >60 years), gender, smoking status. Of 272 eligible and evaluable patients received EGFR-TKI, we found that patients harboring lower CTC levels (<20.5)were associated with longer PFS(432days, 95%CI:332.7-541.3) than those with higher CTC levels (≥20.5)(PFS: 308days, 95%CI:245.3-370.7;P=0.017). Patients with CTC <20.5 had a DCR of 77.11% compared with 58.49% in CTC >20.5 groups (P=0.008), patients with CTC <20.5 had a ORR of 51.20% compared with 33.96% in CTC >20.5 groups (P=0.029). Decreased CTC values correlated well with partial response after one month or three months’ treatment of EGFR-TKI (P=0.0082 and P=0.0023),but not with stable disease (P=0.1843 and P=0.8606).Multivariate analysis showed that CTC level was an independent prognostic factor for PFS (CTC level<20.5 vs ≥20.5,hazard ratio, 0.497; P=0.014).
Conclusion:
The change of CTCs correlated significantly with radiological response. This strategy may enable non-invasive, predictive and prognostic, specific biomarker in patients undergoing targeted therapies.
-
+
P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
P3.02b-104 - Rebiopsy for Patients with Non-Small-Cell Lung Cancer after Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Failure (ID 5808)
14:30 - 14:30 | Author(s): C. Su
- Abstract
Background:
All non-small cell lung cancer patients (NSCLC) with mutant epidermal growth factor receptor (EGFR) eventually develop resistance to EGFR tyrosine kinase inhibitors (TKIs). Rebiopsy and retesting plays more important role in clinical application for exploring resistant mechanisms and determining further therapy strategies. This retrospective study was be performed to determine the percentage of patients who underwent rebiopsy and retesting, and the rebiopsy and retesting effect on clinical strategies and patients prognosis.
Methods:
From October 2011 to March 2016, patients with advanced NSCLC who developed resistance to EGFR-TKIs were included into this study. EGFR mutation detection were performed by ARMS PCR in our institution.
Results:
A total of 539 patients were enrolled in this study with a median progression-free survival time (PFS) of 11.1 months according to RECIST criteria. In all, 297 (55.1%) patients underwent rebiopsy for 178 computed tomography (CT)-guided needle biopsies, 87 serous cavity effusion (including 80 pleural effusion, 3 ascitic fluid and 4 pericardial effusion), 21 superficial lymph node biopsy, 11 other procedures. 354 (65.7%) patients after EGFR-TKIs failure were performed EGFR mutation testing used by 288 rebiopsy and 66 plasma samples. 181 (51.5%) had T790M mutation. In 66 plasma samples, 29 (43.9%) hardored T790M mutation, 23 (34.8%) with mutation in accordance with before EGFR-TKIs treatment, 14 with wild-type EGFR. In all patients, 341 recieved further treatment in our hospital; 236 (69.2%) patients treated with chemotherapy, 43 (12.6%) recieved TKI combined local treatment, 42 (12.3%) changed second or third generation TKIs, 30 switched to other treament. But this part of data still underdone.
Conclusion:
Rebiopsy is feasible in patients after EGFR-TKIs failure. Rebiopsy could effect on further treatment strategies after especially third generarion EGFR-TKI in clinical application. While plasma is also an available surrogate of EGFR mutation testing for patients without suitable lesions for rebiopsy after disease progression.
