CHICAGO — Nivolumab was associated with favorable 2- and 3-year OS and a high durable response rate in ipilimumab-naive patients with metastatic melanoma, according to long-term study results presented at the ASCO Annual Meeting.
“PD-L1 expression is seen on a wide variety of solid tumors and can be upregulated by cytokines, particularly gamma interferon,” researcher F. Stephen Hodi, MD, director of the melanoma center at Dana-Farber Cancer Institute and associate professor of medicine at Harvard Medical School, said during a presentation. “By immunohistochemistry, PD-L1 is expressed in nearly 40% of metastatic melanoma deposits, and can also suppress immunity by binding to CD8.”
F. Stephen Hodi
Hodi and colleagues evaluated data from 107 patients, 25% of whom had received three or more prior therapies other than ipilimumab (Yervoy, Bristol-Myers Squibb). The median age of patients was 61 years, and 97% of patients had an ECOG performance status of 0 to 1.
Patients received one of five doses nivolumab (BMS-936558, Bristol-Myers Squibb) every other week for no more than 96 weeks. Doses were 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg or 10 mg/kg.
The objective response rate from all doses was 32%, and the median duration of response was 22.9 months. Among patients assigned the 3-mg/kg dose — the dose selected for phase 3 trials — 41% demonstrated a response, and the median duration of response was 75 weeks.
Responses were ongoing in 19 of 34 responders (56%) at the time of the analysis. More than half of 21 responders (52%; n=11) who discontinued therapy for a reason other than progressive disease did so after responding for at least 24 weeks, and seven of these patients remained in response for 24 to 56 weeks.
Of the responders, 44% (n=15) demonstrated a response at the time of the first tumor assessment at 8 weeks.
Overall, 48% of patients across all doses achieved 2-year OS and 41% achieved 3-year OS. After that, data appear to start to plateau, Hodi said.
Among all patients, the median PFS was 3.7 months and median OS was 17.3 months. Patients assigned 3-mg/kg doses demonstrated longer median PFS (9.7 months) and OS (20.3 months).
Researchers found no significant difference between prognostic subgroups and clinical response outcomes.
Hodi and colleagues observed immune-related responses in 11 patients.
“With this analysis, it is suggested patients who experience immune-related type responses can have similar OS outcomes as those who experience RECIST responses,” Hodi said.
Researchers then conducted a retrospective analysis on PD-L1 expression in 41 evaluable patients. Overall, patients with PD-L1 expression staining at 5% demonstrated a trend toward improved median OS (not reached vs. 12.5 months) and PFS (9.1 months vs. 1.9 months) compared with those who had PD-L1 expression of 1%.
“We now have to ask ourselves … how we put the data from nivolumab into context in light of what we’re really aiming for, which is long-term benefit for patients with metastatic melanoma,” Hodi said. “What’s the next goal for our community to raise the so-called tail of the curve? Importantly, raising this we can improve the OS for a majority of patients. Can we do this with combinations moving forward, particularly immunotherapy combinations?”
For more information:
Hodi FS. Abstract #9002. Presented at: ASCO Annual Meeting; May 30-June 3, 2014; Chicago.
Disclosure: Researchers report consultant/advisory roles or employment/leadership positions with, stock ownership in, and honoraria, research funding or other remuneration from Amgen, Amplimmune, Anaeropharma, Biologics Human Application Lab, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Jounce Therapeutics, MedImmune, Merck, Nektar, Novartis, Sanofi and Symphogen.