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Hengrui Liang
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EP1.14 - Targeted Therapy (ID 204)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.14-43 - The Safety of First-line and Subsequent Monotherapy of PD-1/PD-L1 Inhibitors in NSCLC: A Meta Analysis (Now Available) (ID 1058)
08:00 - 18:00 | Author(s): Hengrui Liang
- Abstract
Background
With the application of PD-1/PD-L1 inhibitors for non-small cell lung cancer (NSCLC), some agents (pembrolizumab, nivolumab, atezolizumab and durvalumab) were approved not only in subsequent but also first-line therapy. However, the spectrum of side effects in different therapy time might exist heterogeneity. In this meta-analysis, we assessed and compared the safety of PD-1/PD-L1 inhibitors in first or subsequent line therapy, and the systemic-specific spectrum of treatment-related adverse events (trAEs) were summarized.
Method
A comprehensive search of online databases was performed. Incidence and its 95% CI were chosen to assess safety outcomes. The incidence of trAEs were calculated, including discontinuation and death results. Besides, the most common trAEs and system-specific trAEs of nivolumab and atezolizumab in subsequent therapy were also collected based on Common Terminology Criteria for Adverse Events (CTCAE) 4.0.
Result
In total, 13 studies (3180 patients) were included. First-line therapy was associated with more frequent high-grade trAEs and withdrawal rates compared with subsequent line therapy (20.9% vs 14.1%, p=0.000; 8.3% vs 5.1%, p=0.000), while no significantly statistical difference existed according to any grade trAEs or deaths rates (18.9% vs 13.9%, p=0.985; 0.3% vs 0.5%, p=0.554). Basing on CTCAE 4.0, the common system-specific trAEs of first-line and subsequent therapy were semblable, no matter in any grade or high-grade trAEs. For the detailed trAEs, the common trAEs of first-line and subsequent therapy were similar including fatigue, diarrhoea, nausea and the like. However, in the high-grade trAEs, first-line therapy focused more on liver disorders (1.85%), and subsequent therapy was associated with more gastrointestinal disorders (1.73%).
Conclusion
The incidence of high-grade trAEs and withdrawal rates in first-line therapy were higher than in subsequent therapy, possibly because of the different sensitivity and response of the major organs and immune system to PD-1/PD-L1 inhibitors. Besides, the differences of the common high-grade trAEs may be related to the uneven distribution of targets in various organs. These findings indicate that clinicians should pay more attention to heterogeneous side effects when prescribe PD-1/PD-L1 inhibitors in different time of therapy. Further perspective trials and data are warranted to confirm this conclusion and improve clinical medication guidance.
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P2.09 - Pathology (ID 174)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Pathology
- Presentations: 2
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.09-01 - Characteristics of Driver Mutations in Early Lung Adenocarcinoma: From Preinvasive/Minimally invasive to Invasive Adenocarcinoma (Now Available) (ID 1743)
10:15 - 18:15 | Author(s): Hengrui Liang
- Abstract
Background
It is still unclear when the gene mutation occurs during the carcinogenetic process, which progresses from preinvasive to invasive adenocarcinoma. We aim to investigate the driver gene alterations profile of adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC).
Method
A total of 1219 patients with pulmonary nodes smaller than 3 cm were selected for this study. Driver mutation testing was performed with NGS in all resected tumor tissues. The incidence of mutations was calculated and compared among different subtypes. Logistic regression was used to further identify factors that may independently correlate with IAC.
Result
In all 1219 patients with lung adenocarcinoma, 62 were diagnosed as AIS, 208 as MIA and 949 as IAC. Mutations were found in 809 (66.4%) patients. The frequency of mutations increased with the progression of tumor invasiveness: AIS (32.3%), MIA (45.2%) and IAC (73.2%)(P<0.001 between IAC and AIS, P<0.001 between IAC and MIA). The results (Figure 1) also showed an increasing trend towards more driver mutations from AIS to MIA, and to IAC. Multivariate analysis revealed that driver mutations was a factor associated with IAC (OR: 2.39, P<0.001). Of the genetic factors, EGFR, KRAS and ALK alterations were significant indicators of IAC (all P<0.020), and were found increased in IAC compared with AIS/MIA.
Conclusion
Genetic alterations occurs early in the development of lung adenocarcinoma and can be detected even before tumor have acquired malignant potential. Driver mutations gradually increase in tumorigenesis and progression from AIS to MIA, and finally to overt IAC. A better understanding of carcinogenesis in preinvasive/minimally invasive cases may allow the development of effective preventive, screening, and treatment strategies.
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P2.09-04 - The Clinicopathological Characteristics and Prognosis of Lung Cancer with Tumor Spread Through Air Spaces: A Meta-Analysis (Now Available) (ID 1652)
10:15 - 18:15 | Author(s): Hengrui Liang
- Abstract
Background
Background: The clinicopathological characteristics of lung cancer with tumor spread through air spaces (STAS) has not been clearly characterized yet. Also, it is still not clear whether the presence of STAS correlated with worse prognosis in patients with lung cancer. Thus, we aim to systematically evaluate the clinicopathological characteristics and prognosis of the patients with or without STAS undergoing surgical resection for lung cancer.
Method
Materials and Methods: A comprehensive search of online databases was performed. Clinicopathological characteristics, 5-year RFS and OS rate were compared between 2 groups. Cumulative meta-analysis was performed to evaluate the temporal trend of pooled outcomes. Specific subgroups according to different types of lung cancer are examined.
Result
Results: A total of 25 eligible studies including 8494 patients were recruited. STAS occurred in 2881 patients (34%) while non-STAS occurred in 5613 patients (66%). Overall, patients with STAS manifested significantly more aggressive characteristics, including lymphatic invasion (SMD=2.935; P=0.000), pleural invasion (SMD=2.329; P=0.000), vascular invasion (SMD=2.306; P=0.000) as well as lymph node metastasis (OR=3.510; P=0.000). Patients with STAS also correlated with significantly higher pathological stage (OR=2.216; P=0.003), T stage (OR=1.756; P=0.000), N stage (OR=2.395; P=0.000) and larger tumor size (OR=0.275; P=0.001). Meanwhile, the incidence of STAS was significantly associated with the micropapillary (OR=9.792; P=0.000) and solid patterns (OR=2.451; P=0.000). Moreover, the presence of STAS was related to male sex (OR=1.493; P=0.000), smoking history (OR=1.637; P=0.000) and necrosis (OR=2.300; P=0.000). As for the outcomes of the prognosis, patients with STAS linked with significant worse prognosis than those without STAS, including both 5-year RFS (HR=0.585; 95% CI: 0.486–0.684; P=0.000) and 5-year OS rate (HR=0.788; 95% CI: 0.596–0.980; P=0.000).
Conclusion
Conclusions: The presence of STAS was associated with several invasive pathological characteristics, which might explain the worse prognosis in patients with STAS compared with those without STAS.
