Bristol-Myers Squibb's Yervoy improves recurrence-free survival in Phase III melanoma trial

A Phase III trial showed that Bristol-Myers Squibb's Yervoy (ipilimumab) significantly improved recurrence-free survival (RFS) compared to placebo in patients with stage 3 melanoma who are at high risk of recurrence following complete surgical resection, the company reported Monday. "These findings are significant not only because [Yervoy] is the first immune-checkpoint inhibitor to demonstrate an improvement in recurrence-free survival in this earlier treatment setting, but also because this benefit was observed across all patient sub-groups, including those who were at highest risk of recurrence," said study author Alexander Eggermont. The data were presented at the annual ASCO meeting.

In the study, 951 patients with melanoma that had spread to regional lymph nodes were randomised to receive Yervoy or placebo following complete surgical resection. The drugmaker noted that a 25-percent reduction in the risk of recurrence or death was observed, while at three years, an estimated 46.5 percent of patients treated with Yervoy were free of disease recurrence compared to an estimated 34.8 percent of patients on placebo. The median RFS was 26.1 months in the Yervoy arm, versus 17.1 months of the placebo arm.

"These findings demonstrate, for the first time, that Yervoy has the potential to reduce the risk of cancer recurrence at an earlier stage of melanoma and support our belief that immuno-oncology may have broad applicability across lines of therapy and stages of the disease," remarked Bristol-Myers Squibb head of development, Oncology and Immunosciences Michael Giordano.

Bristol-Myers Squibb noted that 48.8 percent of patients in the Yervoy arm discontinued treatment due to adverse effects, with most managed using standard protocols, although five patients in the Yervoy arm died due to the treatment. Conversely, 1.7 percent of patients in the placebo arm experienced treatment-related adverse effects, and no patients died as a result of treatment. Ron Peck, the company's global development leader for Yervoy, said a 10 mg dose of Yervoy was used in the trial and may have contributed to the side effect rate, while a 3 mg dose is being used in later studies.

However oncologist Jeffery Weber of H. Lee Moffitt Cancer Center suggested that the result "raises as many questions as it answers," particularly with regards to cost. Weber estimated that because the trial used a higher dose than that currently approved for Yervoy and treated patients for a longer period, the full regimen would cost as much as $1.5 million per patient. In response, Bristol-Myers Squibb spokeswoman Sarah Koenig said the company is "sensitive to concerns about the rising costs of healthcare, including pharmaceuticals" and is "actively evaluating ways to address other Yervoy dosing regimens being studied" to enable access for patients in need. She added that the drugmaker is "in [the] process of evaluating options based on these results and it is premature to speculate on our regulatory plans."

Yervoy received FDA approval for the treatment of advanced melanoma in March 2011, while the immuno-therapy was later granted clearance in Europe and Australia. The drug is predicted to generate annual revenue of approximately $2 billion by 2020, according to analysts at Cowen & Co.

Separately, Bristol-Myers Squibb on Monday revealed that Yervoy in combination with the experimental PD-1 inhibitor nivolumab was linked to improvements in overall survival in patients with advanced melanoma in an early-stage study.

For related analysis, read FirstWord Lists: A revolution in cancer – a launch calendar for key immuno-oncology indications and Physician Views Poll Results: First-to-market status for Merck & Co.'s MK-3475 in melanoma could open substantial opportunity for off-label front-line usage.

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