DOI: 10.1002/cncr.35185 ISSN: 0008-543X

Association between treatment‐emergent hypertension and survival with lenvatinib treatment for patients with hepatocellular carcinoma in the REFLECT study

Fabio Piscaglia, Kenji Ikeda, Ann‐Lii Cheng, Masatoshi Kudo, Masafumi Ikeda, Valery Breder, Baek‐Yeol Ryoo, Kalgi Mody, Min Ren, Zahra Ramji, Max W. Sung
  • Cancer Research
  • Oncology



Lenvatinib is approved as a first‐line treatment for patients with unresectable and/or recurrent hepatocellular carcinoma (HCC). Lenvatinib achieved promising clinical benefits in REFLECT but was associated with clinically significant treatment‐emergent hypertension (CSTE‐HTN, a grouped term), a common class effect of tyrosine kinase inhibitors. This post hoc analysis assessed the impact of CSTE‐HTN on the efficacy and safety of lenvatinib in HCC.


Patients from REFLECT who received lenvatinib (n = 476) were stratified according to CSTE‐HTN. Tumors were assessed by mRECIST. Overall survival (OS) and progression‐free survival (PFS) were evaluated using landmark analyses at 4 and 8 weeks.


A total of 212 patients in the lenvatinib arm developed CSTE‐HTN, and 264 did not. CSTE‐HTN first occurred at 3.7 weeks (median); the worst grade CSTE‐HTN occurred at 4.1 weeks (median). No patients had life‐threatening CSTE‐HTN and/or died due to CSTE‐HTN. Median OS was numerically longer in patients with versus without CSTE‐HTN (at 4 weeks: 16.3 vs. 11.6 months; hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.621–1.004; at 8 weeks: 13.5 vs. 11.6 months; HR, 0.87; 95% CI, 0.696–1.089). Median PFS was similar between patients with and without CSTE‐HTN (at 4 weeks: 6.6 vs. 6.4 months; HR, 0.887; 95% CI, 0.680–1.157; at 8 weeks: 5.7 vs. 6.4 months; HR, 1.09; 95% CI, 0.84–1.41). Objective response rate was numerically higher in patients with (48.6%) versus without CSTE‐HTN (34.5%).


In this retrospective analysis, CSTE‐HTN was associated with improved OS but not PFS. CSTE‐HTN did not impair the outcomes of patients with HCC treated with lenvatinib when detected early and managed appropriately.

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