Abstract
Purpose
For patients with advanced HCC, predictors of immunotherapy response are scarce, and the benefits of tyrosine kinase inhibitor (TKI) treatment after immunotherapy are unclear. We explored whether clinical features, such as target lesion response, immune-mediated toxicity, or subsequent TKI therapy predict immunotherapy response.
Methods
We retrospectively studied 77 patients with advanced HCC receiving immunotherapy. Patient characteristics and outcomes were assessed using various statistical methods, including the log-rank test and Kaplan–Meier methods. Cox proportional hazard modeling was used for multivariable survival analysis.
Results
For all patients, median overall survival (mOS) was 13 months (95% CI 8–19), and median progression-free survival (mPFS) was 6 months (95% CI 4–10). Patients with partial response (PR) and stable disease (SD) compared to progressive disease (PD) had prolonged mPFS (27 vs. 5 vs. 1 month(s), p < 0.0001) and mOS (not met vs. 11 vs. 3 months, p < 0.0001). Patients with vs. without immune-mediated toxicities trended towards longer mPFS (9 vs. 4 months p = 0.133) and mOS (17 vs. 9 months; p = 0.095). Patients who did vs. did not receive a tyrosine kinase inhibitor (TKI) after immunotherapy had a significantly improved mOS (19 vs. 5 months, p = 0.0024)). Based on multivariate modeling, the hazard ratio (HR) of overall survival (OS) of patients receiving TKI vs. no TKI was 0.412 (p = 0.0043).
Conclusion
We show that disease control predicts prolonged mOS and mPFS. Furthermore, TKI therapy administered after immunotherapy predicts prolonged mOS in patients with advanced HCC.
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Abbreviations
- TKI:
-
Tyrosine kinase inhibitor
- SD:
-
Stable disease
- PD:
-
Disease progression
- PR:
-
Partial response
- PFS:
-
Progression-free survival
- mPFS:
-
Median progression-free survival
- OS:
-
Overall survival
- mOS:
-
Median overall survival
- TSH:
-
Thyroid-stimulating hormone
- PD-L1:
-
Programmed death-ligand 1
- PD-1:
-
Programmed cell death protein 1
- VEGF:
-
Anti-vascular endothelial growth factor
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This work was supported by The Ruesch Center for the Cure of Gastrointestinal Cancers.
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All authors contributed to the research described in this manuscript. Drs. SA, TR, PP, MLH, and ARH were involved with the composition of the manuscript. XG and HW were involved in figure and table generation for the manuscript. All authors viewed and approved the final version of the paper.
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Samantha Armstrong declares that she has no conflict of interest. Tina Roy declares that she has no conflict of interest. Bhavana Singh declares that she has no conflict of interest. Monika Kulasekaran declares that she has no conflict of interest. Fatima Shaukat declares that she has no conflict of interest. Xue Geng declares that she has no conflict of interest. Hongkun Wang declares that she has no conflict of interest. Petra Prins declares that she has no conflict of interest. Reena C. Jha declares that she has no conflict of interest. Marion L. Hartley, PhD declares that she has no conflict of interest. Aiwu Ruth He declares that she has no conflict of interest.
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Armstrong, S., Roy, T., Singh, B. et al. TKIs beyond immunotherapy predict improved survival in advanced HCC. J Cancer Res Clin Oncol 149, 2559–2574 (2023). https://doi.org/10.1007/s00432-022-04115-w
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DOI: https://doi.org/10.1007/s00432-022-04115-w