Second-line Ramucirumab Showcases Survival Benefits in HCC, Irrespective of Extrahepatic Spread

Author(s):

Second-line treatment with ramucirumab produced an overall survival benefit vs placebo in Chinese patients with hepatocellular carcinoma, irrespective of the presence of extrahepatic spread, according to findings from an exploratory analysis of the phase 3 REACH and REACH-2 trials.

Second-line treatment with ramucirumab (Cyramza) produced an overall survival (OS) benefit vs placebo in Chinese patients with hepatocellular carcinoma (HCC), irrespective of the presence of extrahepatic spread (EHS), according to findings from an exploratory analysis of the phase 3 REACH (NCT01140347) and REACH-2 (NCT02435433) trials.¹

Data presented at the 2022 International Liver Cancer Association Conference showed that among patients with EHS, those treated with ramucirumab plus best supportive care (BSC; n = 72) experienced a median OS of 6.9 months vs 4.4 months for those treated with placebo plus BSC (n = 46; HR, 0.719; 95% CI, 0.477-1.085). In those without EHS, the median OS in the ramucirumab (n = 26) and placebo (n = 11) arms was 8.0 months and 6.2 months, respectively (HR, 0.696; 95% CI, 0.310-1.562).

“Compared [with] placebo, OS benefits were observed with ramucirumab in Chinese patients [with HCC] with EHS—regardless of the baseline tumor burden, number of metastatic sites, and maximum target lesion size,” lead study author Yuxian Bai, MD, of the Harbin Medical University Cancer Hospital in Harbin, China, and colleagues, wrote in a poster on the data.

In May 2019, the FDA approved ramucirumab for patients with HCC who have an alpha fetoprotein (AFP) of at least 400 ng/mL and have previously received sorafenib (Nexavar), based on prior data from REACH-2.² Patients treated with ramucirumab experienced a median OS of 8.5 months vs 7.3 months with placebo (HR, 0.71; 95% CI, 0.53-0.95, P = .020).

REACH and REACH-2 both evaluated ramucirumab in patients with HCC who progressed on or were intolerant to sorafenib. Patients were required to have Barcelona Clinic Liver Cancer stage B or C disease, a Child-Pugh score of A, an ECOG performance status of 0 or 1, and an AFP of at least 400 ng/mL.

REACH and REACH-2 randomly assigned patients to received 8 mg/kg of intravenous ramucirumab plus BSC or placebo plus BSC every 2 weeks. Treatment continued until disease progression or intolerable toxicity.

Key stratification factors in REACH-1 were etiology (hepatitis B vs hepatitis C vs other) and geographic region. Patients enrolled to REACH-2 were stratified by macrovascular invasion (yes vs no), performance status (0 vs 1), and geographic regions.

The primary end point of the trials was OS, and secondary end points included progression-free survival (PFS), overall response rate (ORR), safety, and patient-reported outcomes.

This exploratory analysis aimed to evaluate the safety and efficacy of ramucirumab in Chinese patients with EHS using pooled data from patients in REACH-2 (n = 292) and patients in REACH who had an AFP of at least 400 ng/mL (n = 250).

Baseline characteristics for patients with EHS were generally comparable between the 2 treatment arms, except for the median level of AFP. In the patients with EHS who received ramucirumab, the baseline AFP was 5643 ng/mL (range, 1408-41385) compared with 14166 ng/mL (range, 1959-41110) in those with EHS who received placebo.

Ramucirumab provided an OS benefit to patients with EHS, irrespective of baseline tumor burden. Patients with a baseline tumor burden of more than 103.1 mm who received ramucirumab (n = 35) experienced a median OS of 5.8 months vs 3.9 months for those who received placebo (n = 24; HR, 0.749; 95% CI, 0.430-1.305). In patients with EHS and a tumor burden of 103.1 mm or less, the median OS in the ramucirumab (n = 37) and placebo (n = 22) arms was 11.3 and 4.9 months, respectively (HR, 0.740; 95% CI, 0.393-1.391).

In patients with EHS and at least 2 metastatic sites, the median OS in the ramucirumab arm (n = 29) was 5.8 months vs 4.2 months in the placebo arm (n = 21; HR, 0.722; 95% CI, 0.385-1.354). In those with 1 metastatic site, the median OS in the ramucirumab (n = 42) and placebo (n =24) arms was 9.2 months and 4.7 months, respectively (HR, 0.646; 95% CI, 0.358-1.164).

Moreover, patients with EHS and a maximum lesion size of more than 50 mm, the median OS in the ramucirumab arm (n = 30) was 6.9 months compared with 3.9 months in the placebo arm (n = 17; HR, 0.567; 95% CI, 0.244-1.319). In patients with a maximum lesion size of 50 mm or less, the median OS in the ramucirumab (n = 42) and placebo (n = 29) arms was 7.1 months and 4.9 months, respectively (HR, 0.806; 95% CI, 0.492-1.32).

Ramucirumab also provided a PFS benefit vs placebo in patients with EHS (HR, 0.731; 95% CI, 0.478-1.117) and those without EHS (HR, 0.503; 95% CI, 0.233-1.088).

Regarding safety, treatment-emergent adverse effects (TEAEs) of grade 3 or higher occurred in 45.8% of patients with EHS who received ramucirumab compared with 46.7% of those with EHS who were given placebo. Rates of any-grade TEAEs occurred in 97.2% and 91.1% of patients in the investigative and control arms, respectively.

Among those with EHS who received ramucirumab, the most common TEAEs included proteinuria (any grade, 31.9%; grade 3/4/5, 2.8%), increased aspartate aminotransferase (any grade, 23.6%; grade 3/4/5, 6.9%), peripheral edema (any grade, 23.6%), hypoalbuminemia (any grade, 22.2%), fatigue (any grade, 18.1%), decreased platelet count (any grade, 18.1%; grade 3/4/5, 2.8%), anemia (any grade, 16.7%; grade 3/4/5, 5.6%), cough (any grade, 16.7%), abdominal pain (any grade, 13.9%; grade 3/4/5, 1.4%), decreased appetite (any grade, 13.9%), hypertension (any grade, 13.9%; grade 3/4/5, 4.2%), increased blood bilirubin (any grade, 12.5%; grade 3/4/5, 4.2%), insomnia (any grade, 12.5%), abdominal distension (any grade, 11.1%), upper abdominal pain (any grade, 11.1%), dizziness (any grade, 11.1%), and vomiting (any grade, 11.1%; grade 3/4/5, 1.4%).

“The overall positive benefit-risk profile supports the use of ramucirumab in Chinese [patients with] HCC and EHS,” the study authors concluded. “This study is limited by its small sample size, which limits the interpretation of the results in [this population].”

References

Bai Y, Shao G, Chen X, et al. REACH-2 and REACH: An exploratory analysis of efficacy and safety in Chinese hepatocellular carcinoma patients with extrahepatic spread. Presented at: 2022 International Liver Cancer Association Conference; September 1-4, 2022; Madrid, Spain. Abstract P-106
FDA approves ramucirumab for hepatocellular carcinoma. News release. FDA. May 10, 2019. Accessed September 6, 2022. https://bit.ly/2HeWrD7