Abstract 968P
Background
Immune checkpoint inhibitors (ICIs) have changed the therapeutic landscape of many cancers but ICI efficacy varies greatly. Retrospective analyses showed ATB may have a negative impact on ICI efficacy. However, heterogeneous results induced by ATB observed across studies may be due to population diversity, different definitions of ATB use, limited sample size, etc.
Methods
Data from 5 tisle monotherapy studies were analysed. Patients were dichotomized by timing of IV/oral ATB use; ±30 days of Day 1 tisle treatment was ‘ATB+’, otherwise ‘ATB-’. Propensity score weighting was employed to correct for bias from unbalanced baseline characteristics. Survival probability was estimated by the Kaplan–Meier method and compared by log-rank test. Cox model of overall survival (OS) was used to compute hazard ratio (HR) and 95% confidence interval (CI). Landmark analysis was conducted to explore the association of ATB use and OS across time to mitigate guarantee-time bias.
Results
217/1183 (18%) patients received ATB. OS was significantly decreased in the ATB+ group vs the ATB- group (HR: 1.5; 95% CI: 1.3–1.9, p<0.0001). In the ATB+ group, OS was significantly decreased with prophylactic vs non-prophylactic ATB treatment (HR: 2.5; 95% CI: 1.5–4, p<0.0001). A significant association between ATB use and decreased OS was shown in patients with esophageal squamous cell carcinoma (ESCC) (HR: 3.0; 95% CI: 1.3–7.2, p<0.01), hepatocellular carcinoma (HCC) (HR: 1.8; 95% CI: 1.1–2.9, p<0.01) and urothelial carcinoma (UC) (HR: 2.3; 95% CI: 1.3–3.9, p<0.001). A worse trend in OS was observed for non-small cell lung cancer (NSCLC) (HR: 1.6; 95% CI: 0.74–3.6, p=0.26). Landmark analysis identified the time intervals, as related to Day 1 of tisle treatment, when ATB use had a significant negative impact on OS per tumor type: Day -15–45 for ESCC, Day 19–45 for HCC, and Day -5–133 for UC. No significant time interval emerged in NSCLC.
Conclusions
In this pooled analysis, a negative association was observed between ATB use during tisle treatment and OS in a pooled population and in ESCC, HCC and UC. Time intervals in which ATB use had a significant negative impact on OS were identified per indication. Prophylactic ATB use showed a poorer OS outcome vs non-prophylactic ATB use.
Clinical trial identification
Pooled analysis of the following trials: BGB-A317-001; NCT02407990 BGB-A317-102; CTR20160872 BGB-A317-203; NCT03209973 BGB-A317-204; CTR20170071 BGB-A317-208; NCT03419897.
Editorial acknowledgement
Third-party medical writing assistance, under the direction of the authors, was provided by Jenny Feehan, BSc, of Ashfield MedComms, and was funded by BeiGene, Ltd.
Legal entity responsible for the study
BeiGene, Ltd.
Funding
BeiGene, Ltd.
Disclosure
Z. Ren: Financial Interests, Other, Honoraria: BeiGene, AstraZeneca, F. Hffmann-La Roche, and Merck Sharp & Dohme; Financial Interests, Advisory Role: AstraZeneca, F. Hoffmann-La Roche Ltd, Merck. Y. Gao: Financial Interests, Full or part-time Employment: BeiGene, Ltd.; Financial Interests, Stocks/Shares: BeiGene, Ltd.; Financial Interests, Other, Travel, Accommodations, Expenses: BeiGene, Ltd. C. Wei: Financial Interests, Full or part-time Employment: BeiGene, Ltd. X. Li: Financial Interests, Full or part-time Employment: BeiGene, Ltd. S. Liu: Financial Interests, Full or part-time Employment: BeiGene, Ltd. J. Zhang: Financial Interests, Full or part-time Employment: BeiGene, Ltd. L. Wang: Financial Interests, Full or part-time Employment: BeiGene, Ltd. Y. Wu: Non-Financial Interests, Sponsor/Funding: AstraZeneca, Boehringer Ingelheim, BMS, Hengrui, Pfizer and Roche; Non-Financial Interests, Advisory Role: AstraZeneca, Boehringer Ingelheim, Novartis, Merck, MSD, Roche and Takeda; Financial Interests, Other, Honoraria: AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, Hengrui, MSD, Pfizer, Roche and Sanofi.