Ramucirumab Safe and Effective for Patients With Hepatocellular Carcinoma With No Prior Sorafenib Treatment

Ramucirumab demonstrated tolerable safety and meaningful clinical activity in patients with hepatocellular carcinoma and elevated serum α-fetoprotein (AFP) levels who had previously received non-sorafenib systemic therapy.

“Currently, all approved second-line systemic treatments have been studied only after prior sorafenib…The generation of data on the use of second-line systemic therapies following non-sorafenib regimens is of medical and scientific value,” wrote Richard Finn, MD, Geffen School of Medicine at UCLA, Los Angeles, California, and colleagues.

This study reports on the open-label, non-comparative expansion cohort of the global, double-blind phase 3, REACH-2 trial. The study included 47 patients with hepatocellular carcinoma who had received 1 to 2 prior systemic therapies but had not received sorafenib or chemotherapy enrolled between April 27, 2018 and March 29, 2021 at 21 sites across Asia, Europe, and the United States. Patients were treated with 8 mg/kg of ramucirumab once every 14 days. The primary end point was safety, with secondary end points of overall survival (OS), objective response rate (ORR), pharmacokinetics, immunogenicity, and patient-reported outcomes.

At the data cutoff date of May 11, 2021, the median duration of therapy was 8 weeks. There were 3 patients who had dose reductions, due to hypersensitivity, change in mental status, and reduced neutrophil count. The most common all-cause treatment-emergent adverse events were proteinuria (26%) and hypertension (23%) and were predominantly grade 1 to 2 in severity. Grade ≥3 adverse events occurred in 57% of patients, most commonly hypertension (11%%), proteinuria (6%), hyponatremia (6%), and increased aspartate aminotransferase (6%). There were 18 patients who experienced serious adverse events, with 2 patients each experiencing pneumonia and pyrexia as the most common.

The median OS was 8.7 months (95% confidence interval [CI], 4.6 to 12.2) and the ORR was 10.6% (95% CI, 1.8 to 19.5). For patients with an AFP response, survival was longer compared to those patients without an AFP response (11.7 vs 5.6 months; hazard ratio [HR] 0.40; 95% CI, 0.17 to 0.96; P < .03).

"The safety profile of ramucirumab following a non-sorafenib therapy in patients with second- to third-line advanced [hepatocellular carcinoma] was well-tolerated and consistent with the known safety profile of monotherapy ramucirumab. The clinical activity of ramucirumab was also consistent with data from patients with AFP ≥400 ng/mL in REACH and REACH-2,” Dr Finn and colleagues concluded.

Source:

Finn RS, Yau T, Hsu CH, et al. Ramucirumab for patients with advanced hepatocellular carcinoma and elevated alpha fetoprotein following non-sorafenib systemic therapy: An expansion cohort of REACH-2. The Oncologist. Published online October 3, 2022. doi:10.1093/oncolo/oyac183