Abstract 1397P
Background
Despite the novel generations of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) such as osimertinib in managing EGFR-mutated advanced non-small cell lung cancer (NSCLC), patients will usually develop drug resistance. Post-TKI resistance renders the use of novel treatment strategies, for example combining EGFR-TKI with immune checkpoint inhibitors (ICI). However, recent studies on the use of TKI and ICI reported increased risks of toxicities especially interstitial lung diseases (ILD). This finding prompted us to perform a systematic review and meta-analysis to assess the incidence and nature of treatment-related adverse events (trAEs) in combination TKI and ICI in advanced EGFR-mutant NSCLC patients who have received TKI.
Methods
Articles published in English from MEDLINE, EMBASE, and Cochrane databases were searched through March 2020. The incidence of overall and organ-specific trAEs was investigated in randomised and non-randomised controlled trials, single-arm studies and retrospective studies with sequential or concurrent use of TKI and ICI. The pooled incidences were calculated using R package.
Results
Eleven full-text articles were assessed for eligibility. Seven studies fulfilled our selection criteria. The overall incidence of trAEs in combination TKI and ICI was 100% (95% CI 96-100%) for any-grade and 30% (95% CI 12-52%) for high-grade events. Organ-specific trAEs were most frequently observed in the skin (62%, 95% CI 49-74%), gastrointestinal tract (45%, 95% CI 21-88%), followed by ILD (24%, 95% CI 18-31%). ILD was higher in combination therapy than TKI monotherapy [24% (95% CI 18-31%) vs 3% (1-4%), p value <0.001]. High-grade skin and gastrointestinal trAEs were more frequent in combination therapy [(2%, 95% CI 0-8% vs. 0%, 0-1%, p value = 0.082), (4%, 95% CI 0-12% vs. 1%, 0%-2%, p value = 0.076)], reaching borderline significance.
Conclusions
A higher proportion of trAEs especially ILD was observed in combination TKI and ICI compared to TKI alone. Caution has to be taken when interpreting the results owing to the small number of studies included in this meta-analysis.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
V.H.F. Lee: Honoraria (self): AstraZeneca; Advisory/Consultancy: AstraZeneca; Research grant/Funding (self): BMS, Merck Sharp & Dohme; Travel/Accommodation/Expenses: AstraZeneca, Novartis. All other authors have declared no conflicts of interest.