Howard Lim1, Ravi Ramjeesingh2, Dave Liu3, Vincent C Tam4, Jennifer J Knox5, Paul B Card6, Brandon M Meyers7. 1. Department of Medicine, Division of Medical Oncology, BC Cancer - Vancouver Site, University of British Columbia, Vancouver, BC, Canada. 2. Department of Medicine, Division of Medical Oncology, Dalhousie University, Halifax, NS, Canada. 3. Department of Radiology, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada. 4. Tom Baker Cancer Centre, Department of Oncology, University of Calgary, Calgary, AB, Canada. 5. Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada. 6. Kaleidoscope Strategic, Inc, Toronto, ON, Canada. 7. Department of Oncology, Juravinski Cancer Centre, McMaster University, Hamilton, ON, Canada.
Abstract
BACKGROUND: Systemic therapy for hepatocellular carcinoma (HCC) consisting of the tyrosine kinase inhibitor sorafenib has remained unchanged for over a decade, although results from phase III targeted therapy trials have recently emerged. This review considers available phase III evidence on the use and sequencing of targeted therapy for intermediate and advanced non-locoregional therapy (LRT) eligible HCC and discusses implications for clinical practice. METHODS: Published and presented literature on phase III data reporting on targeted therapy for advanced HCC that was not eligible for loco-regional therapies was identified using the key search terms "hepatocellular cancer" AND "advanced" AND "targeted therapy" AND "phase III" OR respective aliases (PRISMA). RESULTS: Ten phase III trials assessed targeted therapy first-line and eight following sorafenib. In the first-line, atezolizumab plus bevacizumab statistically significantly improved overall survival (OS) and patient-reported outcomes (PROs) compared with sorafenib, while lenvatinib demonstrated non-inferior OS. Following progression on sorafenib, statistically significant OS improvements over placebo were seen for cabozantinib and regorafenib in unselected patients and for ramucirumab in those with baseline α-fetoprotein≥400 ng/mL. Based on improved OS and PROs, atezolizumab plus bevacizumab appears to be a preferred first-line treatment option for intermediate or advanced non-LRT eligible HCC. Phase III data informing sequencing of later lines of treatment is lacking. Therefore, sequencing principles are proposed that can be used to guide treatment selection. CONCLUSIONS: Ongoing trials will continue to inform optimal therapy. Multiple targeted therapies have improved OS in intermediate or advanced non-LRT eligible HCC, although optimal sequencing is an area of ongoing investigation.
BACKGROUND: Systemic therapy for hepatocellular carcinoma (HCC) consisting of the tyrosine kinase inhibitor sorafenib has remained unchanged for over a decade, although results from phase III targeted therapy trials have recently emerged. This review considers available phase III evidence on the use and sequencing of targeted therapy for intermediate and advanced non-locoregional therapy (LRT) eligible HCC and discusses implications for clinical practice. METHODS: Published and presented literature on phase III data reporting on targeted therapy for advanced HCC that was not eligible for loco-regional therapies was identified using the key search terms "hepatocellular cancer" AND "advanced" AND "targeted therapy" AND "phase III" OR respective aliases (PRISMA). RESULTS: Ten phase III trials assessed targeted therapy first-line and eight following sorafenib. In the first-line, atezolizumab plus bevacizumab statistically significantly improved overall survival (OS) and patient-reported outcomes (PROs) compared with sorafenib, while lenvatinib demonstrated non-inferior OS. Following progression on sorafenib, statistically significant OS improvements over placebo were seen for cabozantinib and regorafenib in unselected patients and for ramucirumab in those with baseline α-fetoprotein≥400 ng/mL. Based on improved OS and PROs, atezolizumab plus bevacizumab appears to be a preferred first-line treatment option for intermediate or advanced non-LRT eligible HCC. Phase III data informing sequencing of later lines of treatment is lacking. Therefore, sequencing principles are proposed that can be used to guide treatment selection. CONCLUSIONS: Ongoing trials will continue to inform optimal therapy. Multiple targeted therapies have improved OS in intermediate or advanced non-LRT eligible HCC, although optimal sequencing is an area of ongoing investigation.
Authors: Brandon M Meyers; Arndt Vogel; Paul Marotta; Petr Kavan; Laveena Kamboj; Janice Pan; Marc Geadah; David Trueman; Suthakar Sabapathy Journal: Can J Gastroenterol Hepatol Date: 2021-02-23
Authors: Sofia Isolde Bär; Alexandra Dittmer; Bianca Nitzsche; Gohar Ter-Avetisyan; Michael Fähling; Adrian Klefenz; Leonard Kaps; Bernhard Biersack; Rainer Schobert; Michael Höpfner Journal: Int J Oncol Date: 2022-04-29 Impact factor: 5.884