Results from a matching-adjusted indirect comparison (MAIC) suggest that cabozantinib provides two additional months of progression-free survival versus regorafenib in the second-line treatment of advanced hepatocellular carcinoma1

Paris (France), 20 September 2019 – Ipsen (Euronext: IPN; ADR: IPSEY) today presents results from the matching-adjusted indirect comparison (MAIC) of cabozantinib (Cabometyx®) versus regorafenib (Stivarga®) for the second-line treatment (2L) of patients with advanced hepatocellular carcinoma (aHCC) who received sorafenib as the only prior systemic therapy. Using data from the Phase III CELESTIAL and RESORCE trials, the MAIC showed that cabozantinib offers greater efficacy versus regorafenib.

Using data from the Phase III CELESTIAL and RESORCE trials, the MAIC showed that in the 2L CELESTIAL sub-population who had received sorafenib as the only prior systemic therapy, cabozantinib significantly improved progression-free survival (PFS), with an additional 2.4 months provided vs. regorafenib (5.6 months vs. 3.2 months [95% confidence interval (CI): 4.90-7.26], p<0.05). Median overall survival (OS) was also favorable with cabozantinib (11.4 months vs. 10.8 months), though statistical significance was not met.1

Results from MAIC will be presented by Dr. Katie Kelley, oncologist at the University of California, San Francisco and lead investigator, at the 13th Annual Conference of the International Liver Cancer Association (ILCA 2019) taking place on 20-22 September 2019 in Chicago, USA (poster/abstract #P-021).

In the previously presented randomized, double-blind, Phase III CELESTIAL trial evaluating cabozantinib compared with placebo in previously treated patients with aHCC, in the overall CELESTIAL intent-to-treat population, cabozantinib significantly improved median PFS, with an additional 3.3 months provided vs placebo (5.2 months vs. 1.9 months [95% CI, 4.0 to 5.5], p<0.001) and median OS, with an additional 2.2 months vs placebo (10.2 months vs. 8.0 months [95% confidence interval (CI): 9.1 to 12.0), p=0.005).1

“Hepatocellular carcinoma is a devastating disease with only a few treatment options demonstrating survival benefits and many investigational drugs have failed to meet overall survival endpoints in clinical trials,” said Dr. Kelley. “The MAIC analysis brings further insight into the comparative effectiveness of the key second-line treatments for advanced hepatocellular carcinoma, particularly in relation to important endpoints like progression-free survival. These results may support clinicians in making informed treatment decisions in order to deliver optimal care for their patients.”

Grade 3/4 adverse events affecting more than 5% of patients were comparable for the two studies, except for diarrhea which was lower with regorafenib.1

MAICs are a way of providing a timely comparison of the effectiveness of different medical interventions in the absence of head-to-head randomized trials.2 While indirect comparisons of treatments across separate studies can be performed, these analyses may be biased by cross-trial differences in patient populations, sensitivity to modeling assumptions, and differences in the definitions of outcome measures. MAICs use individual patient data (IPD), also referred to as individual-level data, from trials of one treatment to match baseline summary statistics reported from trials of another treatment and reduce observed cross-trial differences.2 After matching, treatment outcomes are compared across balanced trial populations. It should be noted that, even after matching, bias may still occur in MAIC due to imbalance in unobserved factors, and it cannot completely replace a head-to-head randomized and controlled trial.1

“At Ipsen, our mission is to prolong and improve patients’ lives and health outcomes, and we acknowledge the importance of providing healthcare professionals with the best available evidence to achieve these goals for patients,” said Dr. Yan Moore, Ipsen’s Senior Vice President, Head of Oncology Therapeutic Area. “The recent rapid development of new second-line treatments for patients with advanced HCC has led to the generation of information mainly based on placebo-controlled trials. While alternative methodological approaches such as MAIC are not substitutes to evidence-based prospective clinical trials, it is important to recognize the need for further insights into the comparative effectiveness of current treatment approaches.”

1 Abou-Alfa, G.K., et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. NEJM. 2018;379:54-63. Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa1717002. Accessed August 2019.
2 Signorovitch, J.E., et al. Matching-adjusted indirect comparisons: a new tool for timely comparative effectiveness research. Value Health. 2012;15(6):940-7. Available at https://www.ncbi.nlm.nih.gov/pubmed/22999145. Accessed August 2019
3 Bruix, J., et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomized, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;389(10064):56-66. Available at: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)32453-9/fulltext. Accessed August 2019
4 Aggarwal, M., et al. Systemic treatment for hepatocellular carcinoma. Chronic Dis Transl Med. 2018;4(3):148–155. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6160617/. Accessed August 2019.
5 American Institute of Cancer Research. Liver cancer statistics. Available at: https://www.wcrf.org/dietandcancer/cancer-trends/liver-cancer-statistics. Accessed August 2019.
6 European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J. Hepatol. 2018;69(1):182–236. Available at: https://www.journal-of-hepatology.eu/article/S0168-8278(18)30215-0/pdf. Accessed August 2019.

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