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Z. Wang
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MA08 - Treatment Monitoring in Advanced NSCLC (ID 386)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:R. Perez-Soler, T. Reungwetwattana
- Coordinates: 12/06/2016, 11:00 - 12:30, Lehar 3-4
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MA08.07 - Prospective Sequential Counts of Total CTC or cKIT+CTC in Advanced NSCLC with 1st Line Chemotherapy (POLICE) (ID 5857)
11:42 - 11:48 | Author(s): Z. Wang
- Abstract
- Presentation
Background:
Circulating tumor cells (CTCs) have been reported prognostic and predictive in non-small cell lung cancer (NSCLC) and a few of other cancer types. In 1[st] line setting, whether EPCAM[+]CK[+]CD45[-] CTC and/or stem cell-like cKIT[+]EPCAM[+ ]CK[+]CD45[-] CTC enumeration and dynamic changes can be prognostic and/or predictive to standard chemotherapy need further investigation in Chinese patients with NSCLC.
Methods:
A prospective study on the CTC enumeration in advanced NSCLC with 1st line chemotherapy (POLICE) was started by China Thoracic Oncology Group (CTONG). Patients with NSCLC naïve for systemic regimens were enrolled since August 2013. CTCs were detected by Cell Search Platform and identified as positive for EPCAM[+]CK[+]CD45[-] phenotype. CD117 (cKIT) marker was added to test the frequency of stem cell-like cKIT[+]EPCAM[+]CK[+]CD45[- ]CTCs. Primary endpoints were CTC counts and its correlation with first line therapy.
Results:
Totally 180 patients were enrolled. In 174 case total CTC and cKIT[+]CTC positive (cutoff >=1) rates were 38.5% (67/172) vs 14.3% (24/168), 21.8% (31/142) vs 6.3% (9/142), 13.7% (13/95) vs 6.4% (6/94) and 40.4% (38/94) vs 15.0% (13/93) at time-points of baseline, after first-cycle-chemo, after four-cycles-chemo and disease progression. At time immediately after first-cycle-chemo, patients in CTC=0 group got statistically higher ORR (29.0% VS 7.1%, P=0.017) and DCR (74.2% VS 42.9%, P=0.002) than in CTC>=1 group. At time after four-cycles-chemo, patients in CTC=0 group got statistically higher DCR (88.3% VS 58.3%, P=0.026) than in CTC>=1 group. At time either after first-cycle-chemo or after four-cycles-chemo, patients in CTC>=1 group got worse PFS (5.7m VS 4.0m, P=0.025; 6.3m VS 4.0m, P=0.001 ) than in CTC=0 group. At time after first-cycle-chemo, patients in groups cKIT[+]CTC>=1 and cKIT[-]CTC>=1 got worse PFSs (3.1m vs 4.0m vs 5.7m, P=0.001) and worse DCRs (44.4% vs 42.1% vs 73.9%, P=0.009) than in CTC=0 group. For 142 patients categorized into three groups of dynamic CTC decrease (17), CTC unchanged (82), and CTC increase (43), there were significant differences in terms of DCR (71.8% vs 71.6% vs 33.3%, P=0.018) and PFS (5.2m vs 5.6m vs 3.1m, P=0.037).
Conclusion:
In first line setting of advanced NSCLC, at time-points after first-cycle-chemo other than baseline, total CTC or cKIT[+]CTC counts could be predictive for worse DCR or PFS. CTC increase from baseline to after-first-cycle-chemo might be a strong signal for the inefficacy of first line chemotherapy in the NSCLC patients.
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P3.02a - Poster Session with Presenters Present (ID 470)
- 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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P3.02a-020 - Clinical Failure to Crizotinib in Patients with Anaplastic Lymphoma Kinase-Positive Advanced Non-Small-Cell Lung Cancers (ID 4523)
14:30 - 14:30 | Author(s): Z. Wang
- Abstract
Background:
Crizotinib, as the standard treatment for use in first-line treatment of anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer (NSCLC), showed superiority over platinum-based chemotherapy in advanced ALK-positive lung adenocarcinoma.Undoubtedly, the resistance to crizotinib is a current bottleneck which limits its clinical application. However, there are few reports about clinical failure to crizotinib, especially the correlation between the failure patterns of crizotinib and survival benefit.
Methods:
Totally,171 ALK-positive NSCLC patients treated with crizotinib were reviewed at the Guangdong General Hospital in China from October 2010 to July 2016.The status of ALK rearrangement was assessed by Lysis ALK Break Apart fluorescence in situ hybridization,reverse transcription polymerase chain reaction, or Ventana ALK immunohistochemistry.Chi-square test and Kapla-Meier survival curve were used to analyze the results statistically.
Results:
Among enrolled patients,47.5%(81/171) gained secondary resistance,10.5%(18/171) had primary resistance and 4 patients stopped taking crizotinib because of the occurrence of unacceptable toxicities including anasarca,ventricular tachycardia and hepatic insufficiency. Moreover,49 patients had no progression,in which 2 patients had taken crizotinib more than 5 years uninterruptedly.In the patients with secondary resistance (n=81),46 were male and 63 were never smokers.Brain metastases occurred in 27.1%(22/81) at the baseline,half of which(11/22) still had brain progression after the treatment of crizotinib.On the contrary,21 patients without brain metastases at the baseline were evaluated at disease progression because of brain metastases.We classified patients with secondary resistance into several categories according to the failure patterns of crizotinib, such as dramatic,gradual and local progression.There were 47(58.0%), 2(2.5%) and 32(39.5%) patients for dramatic, gradual and local progression respectively.The patients with dramatic progression had an inferior progression-free survival with crizotinib to those with gradual and local progression (9.8 vs 11.9 months),which did not achieve statistical significance.The post progression survival(PPS) of dramatic progression group is 10.4 months.The PPS of other group is 20.5 months comparatively.Patients with dramatic progression showed shorter overall survival when compared with other patients (26.7 vs 41.0 months, P=0.042).
Conclusion:
Dramatic progression was prevalent in ALK-positive lung adenocarcinoma beyond failure to crizotinib, and predicted poor overall survival.
