Comparative Efficacy of Cabozantinib and Ramucirumab After Sorafenib for Patients with Hepatocellular Carcinoma and Alpha-fetoprotein ≥ 400 ng/mL: A Matching-Adjusted Indirect Comparison

Jörg Trojan*, Patrick Mollon, Bruno Daniele, Florence Marteau, Lidia Martín, Yuxin Li, Qing Xu, Fabio Piscaglia, Renata Zaucha, Debashis Sarker, Ho Yeong Lim, Marino Venerito

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Introduction: Cabozantinib and ramucirumab are approved for the treatment of adults with hepatocellular carcinoma (HCC) following prior sorafenib treatment; ramucirumab is restricted to use in patients with serum alpha-fetoprotein (AFP) ≥ 400 ng/mL. This matching-adjusted indirect comparison evaluated the efficacy and safety of both drugs after sorafenib in patients with HCC and AFP ≥ 400 ng/mL. Methods: Individual patient data (IPD) from the CELESTIAL trial (cabozantinib) and population-level data from the REACH-2 trial (ramucirumab) were used. To align with REACH-2, the CELESTIAL population was limited to patients who received first-line sorafenib only and had baseline serum AFP ≥ 400 ng/mL. The IPD from CELESTIAL were weighted to balance the distribution of 11 effect-modifying baseline characteristics with those of REACH-2. Overall survival (OS; primary endpoint) and progression-free survival (PFS) were compared for the CELESTIAL (matching-adjusted) and REACH-2 populations using weighted Kaplan-Meier (KM) curves and parametric (OS, Weibull; PFS, log-logistic) modeling. Rates of treatment-related adverse events (TRAEs) and TRAE-related discontinuations were also compared. Results: After matching and weighting, baseline characteristics were balanced between populations (REACH-2, N = 292; CELESTIAL, effective sample size = 105). Weighted KM estimates for OS (median [95% CI]) were not significantly different between cabozantinib and ramucirumab (10.6 [9.5–17.3] months versus 8.7 [7.3–10.8] months; p = 0.104), but PFS was significantly longer for cabozantinib than for ramucirumab (5.5 [4.6–7.4] months versus 2.8 [2.7–4.1] months; p = 0.016). Parametric modeling results were consistent with the weighted KM analysis. Rates of some grade 3 or 4 TRAEs were lower with ramucirumab than with cabozantinib; however, TRAE-related discontinuation rates were similar (p = 0.271). Conclusion: In this MAIC, cabozantinib significantly prolonged median PFS compared with ramucirumab after prior sorafenib treatment in patients with HCC and AFP ≥ 400 ng/mL; rates of some grade 3 or 4 TRAEs were lower with ramucirumab than cabozantinib but related discontinuation rates were not significantly different between treatments. Trial Registration: Clinical trials.gov identifiers: CELESTIAL trial (NCT01908426) and REACH-2 trial (NCT02435433). Graphic abstract: These slides can be retrieved under Electronic Supplementary Material. [Figure not available: see fulltext.].

Original languageEnglish
Pages (from-to)2472-2490
Number of pages19
JournalADVANCES IN THERAPY
Volume38
Issue number5
DOIs
Publication statusPublished - May 2021

Keywords

  • Alpha-fetoprotein (AFP)
  • Cabozantinib
  • Hepatocellular carcinoma (HCC)
  • Indirect treatment comparison (ITC)
  • Matching-adjusted indirect comparison (MAIC)
  • Monoclonal antibody (mAb)
  • Ramucirumab
  • second-line treatment / 2L treatment
  • Tyrosine kinase inhibitor (TKI)
  • Vascular endothelial growth factor (VEGF)

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