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BARCELONA – For patients with hepatocellular carcinoma (HCC) with elevated alpha-fetoprotein (AFP) levels who have disease progression following first-line sorafenib (Nexavar), the antiangiogenic agent ramucirumab was associated with a modest but significant improvement in overall survival, compared with placebo, a pooled analysis of clinical trial data showed.
Among 316 patients assigned to receive ramucirumab in the phase 3 REACH and REACH-2 trials, median overall survival was 8.1 months, compared with 5.0 months for placebo, an absolute difference of 3.1 months that translated into a hazard ratio favoring ramucirumab of 0.694 (P = .0002), reported Andrew X. Zhu, MD, PhD of the Massachusetts General Hospital Cancer Center in Boston.
Ramucirumab (Cyramza) is a human IgG1 monoclonal antibody directed against ligand activation of the vascular endothelial growth factor receptor 2.
The REACH trial did not meet its primary endpoint of an improvement in overall survival with ramucirumab in an intention-to-treat population. (Lancet Oncol. 2015 Jul;16(7):859-70). REACH-2, however, results of which were presented at the 2018 annual meeting of the American Society of Clinical Oncology (ASCO 2018, Abstract 4003), met its primary endpoint of overall survival with ramucirumab, with a median overall survival of 8.5 months versus 7.3 months for placebo (HR, 0.71; P = .0199) in patients with AFP levels of 400 ng/mL or greater who had experienced disease progression after first-line sorafenib.
The pooled analysis Dr. Zhu presented was designed to provide a better assessment of the efficacy and safety of ramucirumab as a second-line agent in this high-risk population.
In REACH, 250 patients with advanced HCC and AFP 400 ng/mL or greater were enrolled and randomized on a 1:1 basis to ramucirumab or placebo. In REACH 2, patients were randomized on a 2:1 basis to either ramucirumab 8 mg/kg intravenously every 2 weeks (the same dose as in REACH) or placebo. The pooled analysis included 316 patients on ramucirumab and 226 placebo-treated controls.
In each trial, treatment was continued until disease progression or unacceptable toxicity. The primary endpoint was overall survival, and secondary endpoints were progression-free survival, overall response rate, safety, and patient-reported outcomes.
Overall survival in the pooled analysis was as noted before. The benefits of ramucirumab were significantly better for men, for patients younger than 65 years, for patients of white and Asian race, for those with non–hepatitis B or C etiology of liver disease, and in patients with extrahepatic metastases. In addition, those without microvascular invasion, patients with Barcelona Clinic Liver Cancer score C versus B, those with excellent baseline performance status, those who received prior locoregional therapy, and patients who discontinued sorafenib because of disease progression also saw benefit from ramucirumab.
“Ramucirumab’s overall survival treatment benefit was consistent and robust across all subgroups. Sensitivity analyses, include random effect models, were consistent,” Dr. Zhu said.
The median progression-free survival with ramucirumab was 2.8 months, compared with 1.5 months for placebo (P less than .0001). The overall response rate, including all complete and partial responses, was 5.4% for ramucirumab versus 0.9% for placebo (P = .0064). The respective disease control rates, including patients with stable disease, were 56.3% versus 37.2% (P less than .0001).
Adverse events of special interest included grade 3 or greater liver injury or failure in 19.9% of patients on ramucirumab versus 26.5% on placebo, bleeding and/or hemorrhagic events in 4.7% versus 6.7%, and hypertension in 12.7% versus 3.6%.
The REACH trials were supported by Eli Lilly. Dr. Zhu disclosed consulting/advising for Eli Lilly and others, and institutional research from Eli Lilly and others.
SOURCE: Zhu AX et al. ESMO GI 2018, Abstract LBA-001.
BARCELONA – For patients with hepatocellular carcinoma (HCC) with elevated alpha-fetoprotein (AFP) levels who have disease progression following first-line sorafenib (Nexavar), the antiangiogenic agent ramucirumab was associated with a modest but significant improvement in overall survival, compared with placebo, a pooled analysis of clinical trial data showed.
Among 316 patients assigned to receive ramucirumab in the phase 3 REACH and REACH-2 trials, median overall survival was 8.1 months, compared with 5.0 months for placebo, an absolute difference of 3.1 months that translated into a hazard ratio favoring ramucirumab of 0.694 (P = .0002), reported Andrew X. Zhu, MD, PhD of the Massachusetts General Hospital Cancer Center in Boston.
Ramucirumab (Cyramza) is a human IgG1 monoclonal antibody directed against ligand activation of the vascular endothelial growth factor receptor 2.
The REACH trial did not meet its primary endpoint of an improvement in overall survival with ramucirumab in an intention-to-treat population. (Lancet Oncol. 2015 Jul;16(7):859-70). REACH-2, however, results of which were presented at the 2018 annual meeting of the American Society of Clinical Oncology (ASCO 2018, Abstract 4003), met its primary endpoint of overall survival with ramucirumab, with a median overall survival of 8.5 months versus 7.3 months for placebo (HR, 0.71; P = .0199) in patients with AFP levels of 400 ng/mL or greater who had experienced disease progression after first-line sorafenib.
The pooled analysis Dr. Zhu presented was designed to provide a better assessment of the efficacy and safety of ramucirumab as a second-line agent in this high-risk population.
In REACH, 250 patients with advanced HCC and AFP 400 ng/mL or greater were enrolled and randomized on a 1:1 basis to ramucirumab or placebo. In REACH 2, patients were randomized on a 2:1 basis to either ramucirumab 8 mg/kg intravenously every 2 weeks (the same dose as in REACH) or placebo. The pooled analysis included 316 patients on ramucirumab and 226 placebo-treated controls.
In each trial, treatment was continued until disease progression or unacceptable toxicity. The primary endpoint was overall survival, and secondary endpoints were progression-free survival, overall response rate, safety, and patient-reported outcomes.
Overall survival in the pooled analysis was as noted before. The benefits of ramucirumab were significantly better for men, for patients younger than 65 years, for patients of white and Asian race, for those with non–hepatitis B or C etiology of liver disease, and in patients with extrahepatic metastases. In addition, those without microvascular invasion, patients with Barcelona Clinic Liver Cancer score C versus B, those with excellent baseline performance status, those who received prior locoregional therapy, and patients who discontinued sorafenib because of disease progression also saw benefit from ramucirumab.
“Ramucirumab’s overall survival treatment benefit was consistent and robust across all subgroups. Sensitivity analyses, include random effect models, were consistent,” Dr. Zhu said.
The median progression-free survival with ramucirumab was 2.8 months, compared with 1.5 months for placebo (P less than .0001). The overall response rate, including all complete and partial responses, was 5.4% for ramucirumab versus 0.9% for placebo (P = .0064). The respective disease control rates, including patients with stable disease, were 56.3% versus 37.2% (P less than .0001).
Adverse events of special interest included grade 3 or greater liver injury or failure in 19.9% of patients on ramucirumab versus 26.5% on placebo, bleeding and/or hemorrhagic events in 4.7% versus 6.7%, and hypertension in 12.7% versus 3.6%.
The REACH trials were supported by Eli Lilly. Dr. Zhu disclosed consulting/advising for Eli Lilly and others, and institutional research from Eli Lilly and others.
SOURCE: Zhu AX et al. ESMO GI 2018, Abstract LBA-001.
BARCELONA – For patients with hepatocellular carcinoma (HCC) with elevated alpha-fetoprotein (AFP) levels who have disease progression following first-line sorafenib (Nexavar), the antiangiogenic agent ramucirumab was associated with a modest but significant improvement in overall survival, compared with placebo, a pooled analysis of clinical trial data showed.
Among 316 patients assigned to receive ramucirumab in the phase 3 REACH and REACH-2 trials, median overall survival was 8.1 months, compared with 5.0 months for placebo, an absolute difference of 3.1 months that translated into a hazard ratio favoring ramucirumab of 0.694 (P = .0002), reported Andrew X. Zhu, MD, PhD of the Massachusetts General Hospital Cancer Center in Boston.
Ramucirumab (Cyramza) is a human IgG1 monoclonal antibody directed against ligand activation of the vascular endothelial growth factor receptor 2.
The REACH trial did not meet its primary endpoint of an improvement in overall survival with ramucirumab in an intention-to-treat population. (Lancet Oncol. 2015 Jul;16(7):859-70). REACH-2, however, results of which were presented at the 2018 annual meeting of the American Society of Clinical Oncology (ASCO 2018, Abstract 4003), met its primary endpoint of overall survival with ramucirumab, with a median overall survival of 8.5 months versus 7.3 months for placebo (HR, 0.71; P = .0199) in patients with AFP levels of 400 ng/mL or greater who had experienced disease progression after first-line sorafenib.
The pooled analysis Dr. Zhu presented was designed to provide a better assessment of the efficacy and safety of ramucirumab as a second-line agent in this high-risk population.
In REACH, 250 patients with advanced HCC and AFP 400 ng/mL or greater were enrolled and randomized on a 1:1 basis to ramucirumab or placebo. In REACH 2, patients were randomized on a 2:1 basis to either ramucirumab 8 mg/kg intravenously every 2 weeks (the same dose as in REACH) or placebo. The pooled analysis included 316 patients on ramucirumab and 226 placebo-treated controls.
In each trial, treatment was continued until disease progression or unacceptable toxicity. The primary endpoint was overall survival, and secondary endpoints were progression-free survival, overall response rate, safety, and patient-reported outcomes.
Overall survival in the pooled analysis was as noted before. The benefits of ramucirumab were significantly better for men, for patients younger than 65 years, for patients of white and Asian race, for those with non–hepatitis B or C etiology of liver disease, and in patients with extrahepatic metastases. In addition, those without microvascular invasion, patients with Barcelona Clinic Liver Cancer score C versus B, those with excellent baseline performance status, those who received prior locoregional therapy, and patients who discontinued sorafenib because of disease progression also saw benefit from ramucirumab.
“Ramucirumab’s overall survival treatment benefit was consistent and robust across all subgroups. Sensitivity analyses, include random effect models, were consistent,” Dr. Zhu said.
The median progression-free survival with ramucirumab was 2.8 months, compared with 1.5 months for placebo (P less than .0001). The overall response rate, including all complete and partial responses, was 5.4% for ramucirumab versus 0.9% for placebo (P = .0064). The respective disease control rates, including patients with stable disease, were 56.3% versus 37.2% (P less than .0001).
Adverse events of special interest included grade 3 or greater liver injury or failure in 19.9% of patients on ramucirumab versus 26.5% on placebo, bleeding and/or hemorrhagic events in 4.7% versus 6.7%, and hypertension in 12.7% versus 3.6%.
The REACH trials were supported by Eli Lilly. Dr. Zhu disclosed consulting/advising for Eli Lilly and others, and institutional research from Eli Lilly and others.
SOURCE: Zhu AX et al. ESMO GI 2018, Abstract LBA-001.
REPORTING FROM ESMO GI 2018
Key clinical point: Second-line therapy with a vascular endothelial growth factor receptor 2 inhibitor modestly improved survival of patients with advanced hepatocellular carcinoma that progressed after first-line sorafenib.
Major finding: Median overall survival was 8.1 months with ramucirumab versus 5 months for placebo.
Study details: An analysis of pooled data from two phase 3 clinical trials with a total of 316 patients treated with ramucirumab and 226 treated with placebo.
Disclosures: The REACH trials were supported by Eli Lilly. Dr. Zhu disclosed consulting/advising for Eli Lilly and others, and institutional research from Eli Lilly and others.
Source: Zhu AX et al. ESMO GI 2018, Abstract LBA-001.