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Article

Optimizing Sequential Systemic Therapies for Advanced Hepatocellular Carcinoma: A Decision Analysis

1
Department of Health Promotion Sciences Maternal and Infant Care, Section of Gastroenterology & Hepatology, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy
2
Department of Surgical, Oncological and Oral Sciences (Di.Chir.On.S.), University of Palermo, 90127 Palermo, Italy
3
Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy
4
Dipartimento di Scienze Economiche, Aziendali e Statistiche, University of Palermo, 90133 Palermo, Italy
5
U.O. Epidemiologia Clinica, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy
*
Author to whom correspondence should be addressed.
These authors equally contributed to this work.
Cancers 2020, 12(8), 2132; https://doi.org/10.3390/cancers12082132
Received: 30 June 2020 / Revised: 20 July 2020 / Accepted: 27 July 2020 / Published: 31 July 2020
(This article belongs to the Special Issue Theranostic Advances in Hepatobiliary Tumors)
Background: An optimal sequential systemic therapy for advanced hepatocellular carcinoma (HCC) has not been discovered. We developed a decision model based on available clinical trials to identify an optimal risk/benefit strategy for sequences of novel systemic agents. Methods: A Markov model was built to simulate overall survival (OS) among patients with advanced HCC. Three first-line (single-agent Sorafenib or Lenvatinib, and combination of Atezolizumab plus Bevacizumab) followed by five second-line treatments (Regorafenib, Cabozantinib, Ramucirumab, Nivolumab, Pembrolizumab) were compared in fifteen sequential strategies. The likelihood of transition between states (initial treatment, cancer progression, death) was derived from clinical trials. Life-year gained (LYG) was the main outcome. Rates of severe adverse events (SAEs) (≥grade 3) were calculated. The innovative measure, called incremental safety-effectiveness ratio (ISER), of the two best sequential treatments was calculated as the difference in probability of SAEs divided by LYG. Results: Lenvatinib followed by Nivolumab (median OS, 27 months) was the most effective sequence, producing a LYG of 0.75, while Atezolizumab plus Bevacizumab followed by Nivolumab was the safest sequence (SAEs 40%). Accordingly, the net health benefit assessed by ISER favored Lenvatinib followed by Nivolumab, compared to Atezolizumab plus Bevacizumab, followed by Nivolumab in 52% of cases. Conclusion: Further sequential clinical trials or large-scale real-world studies may prove useful to evaluate the net health benefit of the best sequential treatment for advanced HCC. View Full-Text
Keywords: hepatocellular carcinoma; systemic therapy; sequential therapy; tumor progression; survival hepatocellular carcinoma; systemic therapy; sequential therapy; tumor progression; survival
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MDPI and ACS Style

Cabibbo, G.; Celsa, C.; Enea, M.; Battaglia, S.; Rizzo, G.E.M.; Grimaudo, S.; Matranga, D.; Attanasio, M.; Bruzzi, P.; Craxì, A.; Cammà, C. Optimizing Sequential Systemic Therapies for Advanced Hepatocellular Carcinoma: A Decision Analysis. Cancers 2020, 12, 2132. https://doi.org/10.3390/cancers12082132

AMA Style

Cabibbo G, Celsa C, Enea M, Battaglia S, Rizzo GEM, Grimaudo S, Matranga D, Attanasio M, Bruzzi P, Craxì A, Cammà C. Optimizing Sequential Systemic Therapies for Advanced Hepatocellular Carcinoma: A Decision Analysis. Cancers. 2020; 12(8):2132. https://doi.org/10.3390/cancers12082132

Chicago/Turabian Style

Cabibbo, Giuseppe, Ciro Celsa, Marco Enea, Salvatore Battaglia, Giacomo E.M. Rizzo, Stefania Grimaudo, Domenica Matranga, Massimo Attanasio, Paolo Bruzzi, Antonio Craxì, and Calogero Cammà. 2020. "Optimizing Sequential Systemic Therapies for Advanced Hepatocellular Carcinoma: A Decision Analysis" Cancers 12, no. 8: 2132. https://doi.org/10.3390/cancers12082132

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