Hepatic arterial infusion of chemotherapy improves OS in hepatocellular carcinoma subset
Patients with hepatocellular carcinoma and portal vein invasion achieved longer OS with the addition of hepatic arterial cell infusion of FOLFOX to sorafenib, according to results of a randomized phase 3 study published in JAMA Oncology.
Oral sorafenib (Nexavar, Bayer) — the standard first-line treatment for this patient population —has demonstrated limited survival benefit, with median OS of 5.5 months to 7.2 months, according to study background.
“Cisplatin-based hepatic arterial infusion chemotherapy has been widely employed as an alternative therapy to sorafenib for [patients with HCC] with portal vein invasion in Japan,” MinKe He, MD, of the department of hepatobiliary oncology at Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, and colleagues wrote. “This procedure provides direct delivery of chemotherapeutic agents into the tumor-feeding arteries and minimizes systemic toxic effects through first-pass effect in the liver, producing a significantly higher response rate than systemic chemotherapy or sorafenib.”
He and colleagues evaluated the safety and efficacy of hepatic arterial infusion of FOLFOX (oxaliplatin, fluorouracil and leucovorin) plus sorafenib vs. sorafenib monotherapy among 247 patients (median age, 49 years, range, 18-75; men, n = 223) with HCC and portal vein invasion at five hospitals in China.
Eligibility criteria included Child-Pugh A class liver function, ECOG performance status of 0 to 2, no prior treatment for HCC, a minimum of one lesion based on RECIST 1.1 criteria, and sufficient organ function.
The researchers randomly assigned patients to receive 400 mg sorafenib twice daily (n =122) alone or with hepatic arterial cell infusion of FOLFOX (SoraHAIC), consisting of oxaliplatin 85 mg/m2, leucovorin 400 mg/m2 and fluorouracil bolus 400 mg/m2 on day 1 and fluorouracil infusion 2,400 mg/m2 for 46 hours every 3 weeks (n = 125).
OS by intention-to-treat analysis served as the primary endpoint. The researchers evaluated safety among patients who underwent at least one dose of study treatment.
Results showed median OS of 13.37 months (95% CI, 10.27-16.46) in the SoraHAIC group vs. 7.13 months (95% CI, 6.28-7.98) in the sorafenib group (HR = 0.35; 95% CI, 0.26-0.48).
OS rates in the SoraHAIC group vs. the sorafenib group were 96% vs. 87.7% at 3 months, 82.4% vs. 59% at 6 months, and 65.6% vs. 24.6% at 9 months.
The SoraHAIC group demonstrated a higher response rate than the sorafenib group (40.8% vs. 2.46%; P < .001), and longer median PFS (7.03 months; 95% CI, 6.05-8.02 vs. 2.6 months; 95% CI, 2.15-3.05; P < .001).
Multivariable analysis revealed the following independent risk factors for survival: treatment allocation (HR = 3.32; 95% CI, 2.43-4.52); neutrophil-lymphocyte ratio (HR = 1.56; 95% CI, 1.15-2.1); alpha-fetoprotein level (HR = 1.52; 95% CI, 1.12-2.07); presence or absence of extrahepatic sites (HR = 1.66; 95% CI, 1.23-2.34); and portal vein invasion grade Vp4 vs. grade Vp1 to grade Vp2 (HR = 1.63; 95% CI, 1.08-2.46).
Grade 3 to grade 4 adverse events that occurred more frequently in the SoraHAIC group vs. the sorafenib group included neutropenia (9.68% vs. 2.48%), thrombocytopenia (12.9% vs. 4.96%) and vomiting (6.45% vs. 0.83%).
The researchers cited the study’s open-label design as its main limitation, adding that future treatments for patients who had ceased study treatment might be impacted by investigator and patient decisions.
The positive results from this phase 3 trial may support the use of SoraHAIC for patients in China with newly diagnosed, advanced HCC with portal vein thrombosis, according to a related editorial by Lipika Goyal, MD, Motaz Qadan, MD, PhD, and Andrew X. Zhu, MD, PhD, all of Harvard Medical School.
“The generalizability of these results to patients with non-[hepatitis B virus]-related HCC, Western and other Asian populations, and women remains to be determined,” the authors wrote. “Additionally, logistical and technical considerations may limit the application of SoraHAIC to centers with the infrastructure and expertise for serial administration of HAIC.
“While we eagerly await the results from ongoing clinical studies, this trial marks a key step forward in the management of HCC with [portal vein tumor thrombosis] and highlights the importance of multidisciplinary collaboration,” they wrote. – by Jennifer Byrne
Disclosures: The study researchers report no relevant financial disclosures. Goyal reports no relevant financial disclosures. Qadan reports personal fees from Olympus outside the submitted work. Zhu reports personal fees and/or grants from AstraZeneca, Bayer, Bristol-Myers Squibb, Eli Lilly, Eisai, Exelixis, Merck, Novartis and Roche/Genentech.