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Chengzhi Zhou
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EP1.01 - Advanced NSCLC (ID 150)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.01-08 - Efficacy of Osimertinib in Patients of Advanced Non-Small Cell Lung Cancer with Brain Metastasis: A Retrospective Analysis (Now Available) (ID 1656)
08:00 - 18:00 | Author(s): Chengzhi Zhou
- Abstract
Background
Osimertinib (AZD9291) is an oral, irreversible, third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR T790M resistance mutations.The aim of this retrospective study was to evaluate the efficacy of AZD9291 for advanced non-small cell lung cancer(NSCLC) patients with brain metastasis.
Method
We followed up patients diagnosed with advanced non-small cell lung cancer who were detected with EGFR gene mutation and who received EGFR-TKI from 1st October 2006 to 1st June 2018.Patients finally collected were divided into two groups:One group comprised of 45 patients received first-generation or second-generation EGFR-TKI alone,while other group included 45 patients were given AZD9291.And the 95% confidence interval (CI)and the median progression-free survival (mPFS)were calculated by the Kaplan-Meier method.
Result
The median progression-free survival(mPFS) was longer with osimertinib than with standard EGFR-TKIs (14.0 months vs. 11.0 months; 95%Cl: 10.160-13.840, P=0.017). The mPFS of patients with brain metastasis was significantly longer with osimertinib than with standard EGFR-TKIs(13.0 months vs. 7.0 months; 95%CI: 6.087-11.913, P=0.020). The mPFS of patients with osimertinib was longer with combined radiotherapy than with not receive radiotherapy(18.0 months vs. 13.0 months; 95%CI:7.066-18.934, P=0.915).
Conclusion
In patients with non-small cell lung cancer with brain metastases, the median progression-free time of patients with osimertinib was longer than that of patients with first- or second-generation EGFR-TKIs alone, but osimertinib combined with radiotherapy showed no statistical significance compared with no radiotherapy.
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-126 - The Co-Occurring Genomic Landscape of ERBB2 Exon 20 Insertion in Non-Small Cell Lung Cancer (NSCLC) and the Potential Indicator of Response to Afatinib (Now Available) (ID 1284)
09:45 - 18:00 | Author(s): Chengzhi Zhou
- Abstract
Background
Human epidermal growth factor receptor 2 (ERBB2, HER-2) 20 exon insertion (ERBB2ex20ins) has been identified as an oncogenic driver in lung cancer, for which no valid therapy is currently approved. Concurrent alterations may elucidate its refractory features. Previous studies on Afatinib, a pan-ERBB inhibitor, have revealed an inconsistent clinical activity of it for this group of patients.
Method
Plasma or tissue samples of 112 patients with ERBB2ex20ins were performed next generation sequencing (NGS) for 59 or 1021 cancer-related genes in a Clinical Laboratory Improvement Amendments-certified Laboratory from July 2016 to December 2018. The sequencing data of MSKCC Cohort was downloaded from the public Cancer Genome Atlas Database. The clinical outcomes of 18 patients receiving Afatinib treatment were collected by each contributing doctor in charge and pooled for analysis.
Result
Among the 112 patients, most of cases were female (54%, 60/112) and adenocarcinoma (68%, 76/112). Considering the insertions sites, three subtypes were A775ins (71%; 79/112), G776indel (17%; 19/112) and P780ins (12%; 14/112) in the order of frequency. 80.4% (90/112) of patients had at least one additional alteration. The most frequent co-occurring genes were TP53 (66.1%, 74/112), LRP1B (18.2%, 10/55), EPHA5 (9.1%, 5/55), MLL3 (9.1%, 5/55) and RB1 (8.0%; 9/112). Putative other driver aberrations were mutually exclusive from ERBB2ex20ins. Furthermore, cell cycle pathway was the most commonly involved pathway (84.0%; 94/112) of all the concurrent genes. No substantial differences of concurrence in genomic or pathway level were observed among the three ERBB2 insertion subtypes. The co-occurring genomic feature of ERBB2ex20ins in Our Cohort of Chinese people had an overall strong concordance with the MSKCC Cohort from the United States (R2=0.74, P<0.01). For the prognosis, patients had a worse OS when co-occurring mutation in TP53 [median OS:14.5m (95%CI: 12.7m-16.3m) vs 30.3m (95% CI: not reached)], while the OS was not significantly different among three subtypes. The median duration time for patients with disease control of Afatinib was 4.5 months (95%CI: 3.6m-5.4m; range: 2.5m-13.4m). Of note, ERBB2ex20ins in subclonal status was a significantly independent factor relating to shorter PFS of Afatinib [median PFS: 1.2m (95%CI: 0.8-1.6m) vs 4.3m (95%CI: 3.3m-5.3m), P<0.05]. Dynamic detection in two patients found ERBB2 amplification may be a resistance mechanism for Afatinib.
Conclusion
Concurrence of genetic alterations in NSCLC patients with ERBB2ex20ins was common. The complex genomic characteristic should be fully considered by stratifying patients according to potentially relevant co-mutations other than ERBB2 insertion sites in the designing regimens for them. In addition, the therapeutic effect of Afatinib on patient with ERBB2ex20ins is limited, the clonal status of ERBB2ex20ins may be an important factor with prognosis value.
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P2.12 - Small Cell Lung Cancer/NET (ID 180)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.12-22 - Risk Factors for BM Incidence in SCLC: A Predictive Model for SCLC Patients on Brain Metastasis (Now Available) (ID 1299)
10:15 - 18:15 | Author(s): Chengzhi Zhou
- Abstract
Background
As one of the serious complications in patients with lung cancer, brain metastasis (BM) have been demonstrated more common when patients were diagnosing with small-cell-lung cancer (SCLC). After developing a BM, patients’ median overall survival will be obviously shorten. Prophylactic Cranial Irradiation (PCI) used to be an optimal therapy to prevent the occurrence of BM in SCLC patients, while recently its status was shaken. This retrospective study aimed to find out the potential risk factor relative to the incidence of BM and construct a predictive mode for SCLC, also to see the efficiency of PCI on SCLC patients’ ICPFS.
Method
Patients pathologically diagnosed with SCLC were consecutively enrolled from May 1st 2006 to February 15th 2019 and reviewed. The intracranial progression-free survival (ICPFS) were calculated by a Kaplan-Meier approach. And the candidate prognosticators of the ICPFS were checked by COX regression analysis. Using these risk factor and its coefficient obtained in the multivariate analysis , a model were constructed to anticipate the incidence of BM. And the receiver-operating characteristic (ROC) curve was constructed to access the prediction ability.
Result
Totally 261 SCLC patients were eligible for analysis, including 78 cases had developed a BM (29.9%) after the first diagnosis. We used Cox proportional hazards to analyze and adjust the confounding factor to the incidence of BM, and got the result, that there were five factors showed the significance both in Uni-(P<0.15) and multivariate(P<0.05) analysis, including smoking index <400(P=0.017); vascular invasion (P=0.012); number of primary lesion (P=0.042); staging (P=0.018); and hyponatremia (P=0.05). And a predicative model was constructed by using these factors (except the hyponatremia), with an AUC value of 0.743. And we used this model to distinguish low and high risk group. Two groups’ ICPFS showed a remarkable significance (P<0.001). We also simplified it to make it more convenient in clinical work, which also showed an outstanding significance (P<0.001). However, the PCI in our study was not reach the significance, even though it prolonged the ICPFS (P=0.211).
Conclusion
Factors included smoking index >=400, vascular invasion, number of primary lesion, staging, and hyponatremia, increasing the risk of BM occurrence. In the era of individualized treatment, a predictive model based on smoking status and image science can give some suggestions for clinical work by anticipating the highly risky incidence of brain metastasis on SCLC patients.
