Ramucirumab well tolerated in sorafenib-intolerant HCC patients

CHICAGO — Ramucirumab was well tolerated and associated with low rates of discontinuation among patients with advanced hepatocellular carcinoma who were intolerant to first-line treatment with sorafenib, according to data presented at the ASCO Annual Meeting.

The findings are from an exploratory analysis of the phase 3 REACH and REACH-2 trials. Previously, these trials showed that ramucirumab (Cyramza, Eli Lilly) improved OS among patients with advanced HCC and a baseline alpha fetoprotein (AFP) of at least 400 ng/mL who had been treated with sorafenib (Nexavar, Bayer). Results of the REACH-2 trial led to the approval of ramucirumab — a fully human monoclonal antibody and VEGFR2 antagonist — in this patient population.

“Ramucirumab provides significant clinical benefits to patients with advanced HCC and AFP [greater than] 400 ng/mL in the second line,” Josep M. Llovet, MD, founder and director of the Liver Cancer Program and professor of medicine at the Mount Sinai School of Medicine, told HemOnc Today. “This benefit also impacted patients with advanced HCC in the first line who were intolerant to sorafenib.”

Llovet and colleagues conducted the exploratory analysis to further investigate the outcomes of patients who received ramucirumab after discontinuing sorafenib due to intolerance or progressive disease. The researchers first assessed the tolerability and benefit of ramucirumab in a pooled, independent analysis of data from the phase 3 trials, during which patients were randomly assigned to 8 mg/kg of ramucirumab (n = 316) or placebo (n = 226) after first-line treatment with sorafenib. Then, they stratified findings from the pooled analysis by reason for sorafenib discontinuation: intolerance (ramucirumab, n = 42; placebo, n = 28) or progression (ramucirumab, n = 274; placebo, n = 198).

Baseline characteristics were “generally balanced” between patients in the pooled population and treatment arms in each subgroup, according to the researchers. The median duration of prior sorafenib treatment was 2.5 months among patients who were intolerant to sorafenib and 4 months among those who progressed on sorafenib.

The rates of treatment discontinuation with ramucirumab were low, according to the researchers. Overall, 11.9% of patients in the sorafenib-intolerant group and 9.1% in the sorafenib-progression group discontinued ramucirumab due to treatment-related adverse events.

The most common adverse events reported among patients with advanced HCC who received ramucirumab included fatigue, headache, peripheral edema, hypertension, abdominal pain, decreased appetite, proteinuria, nausea and ascites.

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Compared with placebo, the median OS was 10.2 months vs. 6.7 months among patients in the sorafenib-intolerant group (HR = 0.59; 95% CI, 0.34-1.02) and 8 months vs. 4.7 months for those in the sorafenib-progression group (HR = 0.71; 95% CI, 0.58-0.88). Ramucirumab also demonstrated a benefit in median PFS, which was 4.4 months vs. 1.4 months in the sorafenib-intolerant group (HR = 0.32; 95% CI, 0.19-0.55) and 2.7 months vs. 1.6 months in the progression group (HR = 0.64; 0.52-0.79).

“Acknowledging limitations of sample size, the ramucirumab treatment benefit in sorafenib-intolerant patients was consistent with that in the pooled population,” the researchers wrote. “Ramucirumab was well tolerated in sorafenib-intolerant patients with low rates of discontinuation due to related adverse events and no deleterious effects on patient-reported disease symptoms.”

Llovet said additional research is needed to identify the ideal combination strategy for ramucirumab.

“Should this be tyrosine kinase inhibitor plus raubirumab?” he said. “[Or] should this be TKI plus checkpoint inhibitors plus ramucirumab?” – by Stephanie Viguers

Reference:

Llovet JM, et al. Abstract 4073. Presented at: ASCO Annual Meeting; May 31- June 4, 2019; Chicago.

Disclosure: Llovet reports receiving consulting or advisory role fees from Bayer, Bristol-Myers Squibb, Celsion, Eisai, Eli Lilly, Exelixis, Glycotest and Incyte; research funding on behalf of his institution from Bayer Schering Pharma, Blueprint Medicines, Bristol-Myers Squibb and Eisai; as well as travel accommodations and expenses paid by Bayer.