Trial reportAdvances in therapy2021
Comparative Efficacy of Cabozantinib and Ramucirumab After Sorafenib for Patients with Hepatocellular Carcinoma and Alpha-fetoprotein ≥ 400 ng/mL: A Matching-Adjusted Indirect Comparison.
Trial report in Advances in therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 3, Randomized, Double-blind, Controlled Study of Cabozantinib (XL184) vs Placebo in Subjects With Hepatocellular Carcinoma Who Have Received Prior Sorafenib
Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of Ramucirumab and Best Supportive Care (BSC) Versus Placebo and BSC as Second-Line Treatment in Patients With Hepatocellular Carcinoma and Elevated Baseline Alpha-Fetoprotein (AFP) Following First-Line Therapy With Sorafenib
Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- Advancing Systemic Treatment beyond First Line for Advanced Hepatocellular Carcinoma.Current oncology reports · 2026Review
- Tumor-based biomarkers and circulating tumor DNA for precision medicine in advanced hepatocellular carcinoma.Clinical and molecular hepatology · 2026Review
- Prognostic impact of primary versus secondary resistance to sorafenib in patients with HCC.Therapeutic advances in medical oncology · 2025Article
- Immunotherapy in hepatocellular carcinoma: how will it reshape treatment sequencing?Therapeutic advances in medical oncology · 2023Review
- TKI or TKI combined with PD-1 inhibitors as second-line treatment for HCC patients after sorafenib failure.Frontiers in pharmacology · 2022Article
- Real-world efficacy and safety of cabozantinib in Korean patients with advanced hepatocellular carcinoma: a multicenter retrospective analysis.Therapeutic advances in medical oncology · 2022Article
- Predictors of Mortality for Patients with COVID-19 in the Rural Appalachian Region.International journal of general medicine · 2022Article
- Systemic therapy for advanced hepatocellular carcinoma: consideration for selecting second-line treatment.Journal of liver cancer · 2021Review
- Cabozantinib for HCC Treatment, From Clinical Back to Experimental Models.Frontiers in oncology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 10 institutions in 8 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionCabozantinib 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.
methodsIndividual 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.
resultsAfter 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).
conclusionIn 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 registrationClinical trials.gov identifiers: CELESTIAL trial (NCT01908426) and REACH-2 trial (NCT02435433). These slides can be retrieved under Electronic Supplementary Material.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.