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Peilin Pang
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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): Peilin Pang
- 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.
