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J. Li
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JCES01 - Joint IASLC - Chinese Society for Clinical Oncology - Chinese Alliance Against Lung Cancer Session (ID 413)
- Event: WCLC 2016
- Type: Joint Chinese / English Session
- Track:
- Presentations: 1
- Moderators:F.R. Hirsch, C. Bai
- Coordinates: 12/04/2016, 08:00 - 11:45, Stolz 1
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JCES01.16 - A MET Inhibitor in the Treatment of Metastatic Non Small Cell Lung Cancer with MET Amplification (ID 7058)
08:00 - 11:45 | Author(s): J. Li
- Abstract
Background:
Amplification of the mesenchymal-epithelial transition factor (MET) gene plays a vital role in non-small cell lung cancer (NSCLC). The anti-MET therapeutic strategies are still unclear in epidermal growth factor receptor (EGFR) mutant patients and EGFR-naive patients. Aims of our study are to discuss role of MET amplification in Chinese NSCLC patients, and evaluate the antitumor activity of crizotinib (MET inhibitor) in Chinese NSCLC patients with MET gene amplification.
Methods:
From Jun 2015 to Jan 2016, we detected 11 metastatic NSCLC patients with MET amplification by fluorescence in situ hybridization (FISH). MET amplification was defined as gene focal amplification or high polysomy (at least 15% cells with ≥5 copy numbers). Patients with MET de novo amplification received crizotinib, patients with concomitant MET acquired amplification and EGFR mutation received combined therapy of EGFR-tyrosine kinase inhibitors (TKIs) (gefitinib, erlotinib, icotinib)and crizotinib. All enrolled subjects received tumor measurement according to RECIST1.1
Results:
The frequency of MET de novo amplification was 54.5%(6/11), and that of concomitant MET acquired amplification and EGFR mutation was 45.5%(5/11) respectively. 4 of 6 patients with MET de novo amplification received crizotinib, 2 patients had partial response (PR), 1 patient had stable disease (SD), 1 patient died due to heart disease. Response rate (RR) of crizotinib was 50%(2/4). Encouraging response was observed in one case, a CT scan performed 31 days after starting crizotinib revealed 42.2% decrease in tumor measurement, until now, a 7-month CT revealed 60.0% decrease. 3 of 5 patients with concomitant MET acquired amplification and EGFR mutation received the combined therapy of EGFR-TKIs and crizotinib. 1 patient achieved PR, 2 patients had SD. RR of combined therapy was 33.3%(1/3). Dramatic response was observed in one case with combined therapy, a 2-month CT revealed 31.0% decrease in tumor measurement.
Conclusion:
According to our study, patients with MET amplification benefited from crizotinib, and RR was inspiring. Patients with concomitant MET acquired amplification and EGFR mutation need combined targeted therapy.
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P2.03a - Poster Session with Presenters Present (ID 464)
- 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)
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P2.03a-068 - Impact of Platinum/Pemetrexed versus Other Platinum-Based Regimens on Adjuvant Chemotherapy in Resected Adenocarcinoma Lung Cancer (ID 4590)
14:30 - 15:45 | Author(s): J. Li
- Abstract
Background:
Adjuvant chemotherapy improves the survival for completely resected non-small cell lung cancer (NSCLC) patients. Platinum/pemetrexed is known to be less toxicity, better compliance and longer survival in advanced non-squamous NSCLC, but the survival outcome compared with other regimens in adjuvant setting is still unknown. This report described the survival in adjuvant chemotherapy for lung adenocarcinoma with platinum/pemetrexed versus other platinum-based doublets.
Methods:
389 completely radical surgery lung adenocarcinoma patients who received adjuvant chemotherapy with platinum/pemetrexed regimen (Group A, n=143) and non-pemetrexed platinum-based regimens (Group B, n=246) were analyzed retrospectively. Primary end point was disease-free survival (DFS). Propensity score matching (PSM) allowed best matched pairs for platinum/pemetrexed versus other platinum-based doublets for comparison of survival and adverse events.
Results:
PSM created treatment groups for platinum/pemetrexed versus non-pemetrexed regimen (125 pairs), docetaxel and paclitaxel (107 pairs), gemcitabine (56 pairs), and vinorelbine (24 pairs)-contained doublets, respectively. Although DFS was not significantly different between Group A and B (P=0.1643)(Figure A), in 125 PSM pairs, DFS was considerably better in patients who received platinum/pemetrexed regimen (P=0.0079)(Figure B). From the subgroup analysis, Pemetrexed benefit is consistent across different subgroups, and especially aging(>65) was associated with the decision to use platinum/pemetrexed (HR=0.25,95%CI 0.09-0.73, P=0,011). Furthermore, platinum/pemetrexed was associated with several significantly lower hematological and non-hematological AE rates, such as versus gemcitabine (Leukopenia: RR 0.514, p=0.001; Neutropenia: RR 0.688, p=0.002) and paclitaxel- and docetaxel-based chemotherapy (Leukopenia： RR 0.685, p=0.019; Neutropenia: RR 0.805, p=0.032).Figure 1
Conclusion:
Adjuvant chemotherapy with platinum/pemetrexed shows both better disease-free survival and less clinical toxicity than other non-pemetrexed based doublets in completely resected adenocarcinoma lung cancer.
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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)
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P2.03b-018 - Clinical Data from the Real World: Efficacy of Crizotinib in Chinese Patients with Advanced ALK+ Non-Small Cell Lung Cancer and Brain Metastases (ID 4091)
14:30 - 15:45 | Author(s): J. Li
- Abstract
Background:
Brain metastasis in NSCLC patients is often considered as a terminal stage of advanced disease. Crizotinib is a small-molecule tyrosine kinase inhibitor (TKI) for ALK-rearranged NSCLC patients that can improve systemic outcomes. Herein, a retrospective analysis of Crizotinib was performed in advanced ALK-rearranged NSCLC patients with brain metastases, to explore how Crizotinib affects the control of brain metastases and the overall prognosis in Chinese population in the real world.
Methods:
Advanced NSCLC patients with brain metastases who underwent Crizotinib treatment at the Cancer Hospital of the Chinese Academy of Medical Sciences between April 2013 and April 2015 were included. ALK translocation was determined by FISH, Ventana IHC test or RT-PCR. Brain metastases were diagnosed by CT or MRI.
Results:
A total of 34 patients were enrolled, of whom 20 patients had baseline brain metastases at the initiation of Crizotinib treatment. For patients with baseline metastases, overall survival (OS) after brain metastases was significantly longer, compared with those developing brain metastases during Crizotinib treatment (median OS, not reached vs. 10.3 months, p = 0.001). Among all the patients treated with chemotherapy at the first line, OS after brain metastases in patients with baseline brain metastases was significantly superior than those without (p = 0.023). Whereas, patients receiving Crizotinib at the first line with baseline brain metastases didn’t demonstrate such superior (p = 0.089). Among patients who developed brain metastases during Crizotinib treatment, for those receiving chemotherapy at the first line, though the result was not significant by the cut-off date, time to brain metastases was longer, compared with patients receiving Crizotinib at the first line (median time to brain metastases, 17.1 months vs. 10.5 months, p = 0.072).Figure 1
Conclusion:
Chinese ALK-rearranged NSCLC patients with baseline brain metastases may benefit more from Crizotinib than those developing brain metastases during Crizotinib treatment.
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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)
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P3.02b-085 - The Combination Therapy of S-1 and the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors beyond Progressive Disease (ID 4078)
14:30 - 15:45 | Author(s): J. Li
- Abstract
Background:
There is no optimal therapy established for those who have progressed with the Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI). And some preclinical study indicated that the addition of S-1 to EGFR-TKIs might overcome EGFR-TKI resistance. This study was conducted to investigate the efficacy and safety of the combination therapy of S-1 and EGFR-TKIs for patients failed the previous EGFR-TKI treatments.
Methods:
All patients who received the combination therapy of S-1 and EGFR-TKIs beyond progressive disease with EGFR-TKI monotherapy in the Cancer Hospital, the Chinese Academy of Medical Sciences between 2013 and 2016 with complete records were enrolled in this study. The primary endpoint was progression-free survival (PFS), while the disese control rate and safty were secondary endpoints. Multivariate analysis for survival was conducted including age, gender, initiation of EGFR-TKI, the choice of EGFR-TKI, the best efficacy while using EGFR monotherapy and the choice of S-1 and EGFR-TKI.
Results:
A total of 43 non-small-lung cancer (NSCLC) patients who met the inclusion criteria were enrolled in this study. The median PFS for all patients was 5.47 months (95% confidence interval [CI] 3.444-7.489). The disease control rate is 67.4%(29/43). There was no grade 4 toxicity and no grade 3 hematologic toxicity in this study. One patient has grade 3 elevated total serum bilirubin. Cox analysis showed that the combination treatment of S-1 and erlotinib was associated with decreased PFS comparing the gefitinib (hazards ratio[HR] 8.401, 95% CI 2.781-25.379, p<0.001). Besides, male (HR 0.389, 95%CI 0.162-0.934, p=0.035) and patients with SD (HR 0.303, 95%CI 0.124-0.471, p=0.009) or PD (HR 0.031, 95%CI 0.002-0.450, p=0.011) in the monotherapy of EGFR-TKIs were associated with increased PFS.
Conclusion:
The combination treatment of S-1 and EGFR-TKIs is effective and well-tolerated treatment for those failed prior EGFR-TKI. This strategy is promising to overcome EGFR-TKI resistance in NSCLC. A prospective study will be needed to confirm our studys.
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P3.02c - Poster Session with Presenters Present (ID 472)
- 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)
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P3.02c-008 - A MET Inhibitor in the Treatment of Metastatic Non Small Cell Lung Cancer with MET Amplification (ID 3908)
14:30 - 15:45 | Author(s): J. Li
- Abstract
Background:
Amplification of the mesenchymal-epithelial transition factor (MET) gene plays a vital role in non-small cell lung cancer (NSCLC). The anti-MET therapeutic strategies are still unclear in epidermal growth factor receptor (EGFR) mutant patients and EGFR-naive patients. Aims of our study are to discuss role of MET amplification in Chinese NSCLC patients, and evaluate the antitumor activity of crizotinib (MET inhibitor) in Chinese NSCLC patients with MET gene amplification.
Methods:
From Jun 2015 to Jan 2016, we detected 11 metastatic NSCLC patients with MET amplification by fluorescence in situ hybridization (FISH). MET amplification was defined as gene focal amplification or high polysomy (at least 15% cells with ≥5 copy numbers). Patients with MET de novo amplification received crizotinib, patients with concomitant MET acquired amplification and EGFR mutation received combined therapy of EGFR-tyrosine kinase inhibitors (TKIs) (gefitinib, erlotinib, icotinib)and crizotinib. All enrolled subjects received tumor measurement according to RECIST1.1
Results:
The frequency of MET de novo amplification was 54.5%(6/11), and that of concomitant MET acquired amplification and EGFR mutation was 45.5%(5/11) respectively. 4 of 6 patients with MET de novo amplification received crizotinib, 2 patients had partial response (PR), 1 patient had stable disease (SD), 1 patient died due to heart disease. Response rate (RR) of crizotinib was 50%(2/4). Encouraging response was observed in one case, a CT scan performed 31 days after starting crizotinib revealed 42.2% decrease in tumor measurement, until now, a 7-month CT revealed 60.0% decrease. 3 of 5 patients with concomitant MET acquired amplification and EGFR mutation received the combined therapy of EGFR-TKIs and crizotinib. 1 patient achieved PR, 2 patients had SD. RR of combined therapy was 33.3%(1/3). Dramatic response was observed in one case with combined therapy, a 2-month CT revealed 31.0% decrease in tumor measurement.
Conclusion:
According to our study, patients with MET amplification benefited from crizotinib, and RR was inspiring. Patients with concomitant MET acquired amplification and EGFR mutation need combined targeted therapy.
