INTRODUCTION: Combining an immune checkpoint inhibitor with a targeted antiangiogenic agent may leverage complementary mechanisms of action for the treatment of advanced/metastatic hepatocellular carcinoma (aHCC). Avelumab is a human anti-PD-L1 IgG1 antibody with clinical activity in various tumor types; axitinib is a selective tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1, 2, and 3. We report the final analysis from VEGF Liver 100 (NCT03289533), a phase 1b study evaluating safety and efficacy of avelumab plus axitinib in treatment-naive patients with aHCC. METHODS: Eligible patients had confirmed aHCC, no prior systemic therapy, ≥1 measurable lesion, Eastern Cooperative Oncology Group performance status ≤1, and Child-Pugh class A disease. Patients received avelumab 10 mg/kg intravenously every 2 weeks plus axitinib 5 mg orally twice daily until progression, unacceptable toxicity, or withdrawal. Endpoints included safety and investigator-assessed objective response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and modified RECIST (mRECIST) for HCC. RESULTS: Twenty-two Japanese patients were enrolled and treated with avelumab plus axitinib. The minimum follow-up was 18 months as of October 25, 2019 (data cutoff). Grade 3 treatment-related adverse events (TRAEs) occurred in 16 patients (72.7%); the most common (≥3 patients) were hypertension (n = 11 [50.0%]), palmar-plantar erythrodysesthesia syndrome (n = 5 [22.7%]), and decreased appetite (n = 3 [13.6%]). No grade 4 TRAEs or treatment-related deaths occurred. Ten patients (45.5%) had an immune-related AE (irAE) of any grade; 3 patients (13.6%) had an infusion-related reaction (IRR) of any grade, and no grade ≥3 irAE and IRR were observed. The objective response rate was 13.6% (95% CI: 2.9-34.9%) per RECIST 1.1 and 31.8% (95% CI: 13.9-54.9%) per mRECIST for HCC. CONCLUSION: Treatment with avelumab plus axitinib was associated with a manageable toxicity profile and showed antitumor activity in patients with aHCC.
INTRODUCTION: Combining an immune checkpoint inhibitor with a targeted antiangiogenic agent may leverage complementary mechanisms of action for the treatment of advanced/metastatic hepatocellular carcinoma (aHCC). Avelumab is a human anti-PD-L1 IgG1 antibody with clinical activity in various tumor types; axitinib is a selective tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1, 2, and 3. We report the final analysis from VEGF Liver 100 (NCT03289533), a phase 1b study evaluating safety and efficacy of avelumab plus axitinib in treatment-naive patients with aHCC. METHODS: Eligible patients had confirmed aHCC, no prior systemic therapy, ≥1 measurable lesion, Eastern Cooperative Oncology Group performance status ≤1, and Child-Pugh class A disease. Patients received avelumab 10 mg/kg intravenously every 2 weeks plus axitinib 5 mg orally twice daily until progression, unacceptable toxicity, or withdrawal. Endpoints included safety and investigator-assessed objective response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and modified RECIST (mRECIST) for HCC. RESULTS: Twenty-two Japanese patients were enrolled and treated with avelumab plus axitinib. The minimum follow-up was 18 months as of October 25, 2019 (data cutoff). Grade 3 treatment-related adverse events (TRAEs) occurred in 16 patients (72.7%); the most common (≥3 patients) were hypertension (n = 11 [50.0%]), palmar-plantar erythrodysesthesia syndrome (n = 5 [22.7%]), and decreased appetite (n = 3 [13.6%]). No grade 4 TRAEs or treatment-related deaths occurred. Ten patients (45.5%) had an immune-related AE (irAE) of any grade; 3 patients (13.6%) had an infusion-related reaction (IRR) of any grade, and no grade ≥3 irAE and IRR were observed. The objective response rate was 13.6% (95% CI: 2.9-34.9%) per RECIST 1.1 and 31.8% (95% CI: 13.9-54.9%) per mRECIST for HCC. CONCLUSION: Treatment with avelumab plus axitinib was associated with a manageable toxicity profile and showed antitumor activity in patients with aHCC.
Authors: Richard S Finn; Shukui Qin; Masafumi Ikeda; Peter R Galle; Michel Ducreux; Tae-You Kim; Masatoshi Kudo; Valeriy Breder; Philippe Merle; Ahmed O Kaseb; Daneng Li; Wendy Verret; Derek-Zhen Xu; Sairy Hernandez; Juan Liu; Chen Huang; Sohail Mulla; Yulei Wang; Ho Yeong Lim; Andrew X Zhu; Ann-Lii Cheng Journal: N Engl J Med Date: 2020-05-14 Impact factor: 91.245
Authors: Toni K Choueiri; James Larkin; Mototsugu Oya; Fiona Thistlethwaite; Marcella Martignoni; Paul Nathan; Thomas Powles; David McDermott; Paul B Robbins; David D Chism; Daniel Cho; Michael B Atkins; Michael S Gordon; Sumati Gupta; Hirotsugu Uemura; Yoshihiko Tomita; Anna Compagnoni; Camilla Fowst; Alessandra di Pietro; Brian I Rini Journal: Lancet Oncol Date: 2018-03-09 Impact factor: 41.316
Authors: Christopher R Heery; Geraldine O'Sullivan-Coyne; Ravi A Madan; Lisa Cordes; Arun Rajan; Myrna Rauckhorst; Elizabeth Lamping; Israel Oyelakin; Jennifer L Marté; Lauren M Lepone; Renee N Donahue; Italia Grenga; Jean-Marie Cuillerot; Berend Neuteboom; Anja von Heydebreck; Kevin Chin; Jeffrey Schlom; James L Gulley Journal: Lancet Oncol Date: 2017-03-31 Impact factor: 41.316
Authors: Benjamin Boyerinas; Caroline Jochems; Massimo Fantini; Christopher R Heery; James L Gulley; Kwong Yok Tsang; Jeffrey Schlom Journal: Cancer Immunol Res Date: 2015-05-26 Impact factor: 11.151
Authors: Yuhui Huang; Jianping Yuan; Elda Righi; Walid S Kamoun; Marek Ancukiewicz; Jean Nezivar; Michael Santosuosso; John D Martin; Margaret R Martin; Fabrizio Vianello; Pierre Leblanc; Lance L Munn; Peigen Huang; Dan G Duda; Dai Fukumura; Rakesh K Jain; Mark C Poznansky Journal: Proc Natl Acad Sci U S A Date: 2012-10-08 Impact factor: 11.205
Authors: Manish R Patel; John Ellerton; Jeffrey R Infante; Manish Agrawal; Michael Gordon; Raid Aljumaily; Carolyn D Britten; Luc Dirix; Keun-Wook Lee; Mathew Taylor; Patrick Schöffski; Ding Wang; Alain Ravaud; Arnold B Gelb; Junyuan Xiong; Galit Rosen; James L Gulley; Andrea B Apolo Journal: Lancet Oncol Date: 2017-12-05 Impact factor: 41.316
Authors: Mohammad Javed Ansari; Dmitry Bokov; Alexander Markov; Abduladheem Turki Jalil; Mohammed Nader Shalaby; Wanich Suksatan; Supat Chupradit; Hasan S Al-Ghamdi; Navid Shomali; Amir Zamani; Ali Mohammadi; Mehdi Dadashpour Journal: Cell Commun Signal Date: 2022-04-07 Impact factor: 5.712