Robert Ferris, MD, PhD
Treatment options for patients with head and neck cancer who progress after chemotherapy are limited.
“This is a setting of disease where there are really no effective systemic agents,” says Robert Ferris, MD, PhD, co-leader of the Cancer Immunology Program at the University of Pittsburgh Cancer Institute. “Creating a new standard of care has been evasive and difficult for this population of patients with very rapid progression.”
Recent data from the phase III CheckMate-141 study, in which single-agent nivolumab (Opdivo) reduced the risk of death by 30% and doubled 1-year overall survival (OS) rates compared with investigator's choice of therapy, offers significant promise for those with advanced platinum-refractory head and neck cancer, says Ferris, an investigator on the CheckMate-141 study.
“What we have seen with a randomized phase III trial is the establishment of a new standard of care,” he says. “This will come about in new approvals, new trials, and combinations and, hopefully, this will transform the way we think about head and neck cancer.”
The CheckMate-141 study demonstrated a median OS with nivolumab of 7.5 months compared with 5.1 months with investigator's choice of therapy (HR, 0.70; 95% CI, 0.51-0.96; P
= .0101). Only 13.1% of patients experienced grade 3/4 adverse events with nivolumab versus 35.1% with investigator's choice.
In April 2016, nivolumab received a breakthrough therapy designation by the FDA for this patient population. Updated data from CheckMate-141 will be presented in June at the 2016 ASCO Annual Meeting.
In an interview with OncLive
, Ferris further explains the potential of nivolumab, its future, and its limitations in the treatment of patients with head and neck cancer.
OncLive: Can you explain the significance of Checkmate-141?
: This is the first positive randomized phase III trial in head and neck cancer in over a decade. The Checkmate-141 trial presented data using the anti–PD-1 monoclonal antibody nivolumab, which was compared in a 2:1 randomization in favor of nivolumab against standard of care, which was investigator’s choice chemotherapy. In the comparison arm, patients could receive either cetuximab or methotrexate docetaxel.
In the trial, one of the major eligibility requirements is that patients had to progress within 6 months of platinum-based therapy. That could be in the locally advanced or in the recurrent metastatic setting. Some physicians look at Checkmate-141 as a second-line trial; however, it is better perceived as a platinum-refractory population.
Whether patients progressed in the first-, second-, or third-line setting, they had to, at some point, progress within 6 months of platinum therapy. That selects for a very rapidly progressing group of patients for whom we have no effective therapies. To have an OS endpoint met, which was the primary endpoint of this study, is significant. When the study was stopped early, this permitted patients to have access and cross over to the other arm because of the OS benefit. A hazard ratio of .70 indicates a 30% reduction in risk of death.
In addition, a landmark analysis—indicting the percentage of individuals who were alive at 1 year—may be better than even a response rate. In this case, the nivolumab treatment arm had 36% of the patients alive at 1 year, compared with 16.5% in the control arm. There was a 20% increase in patients alive at 1 year, who were spending time with their families and enjoying holidays. This is extremely gratifying for those of us who participated in this trial.
What should community oncologists take away from these findings?
The bottom line is that 20% more patients are alive at 1 year and the grade 3/4 adverse events were only present in 13% of the nivolumab arm. Therefore, we really have a “Goldilocks”—an effective agent with one-third of the grade 3/4 adverse events than with traditional chemotherapy. This was the outcome we were hoping for. Obviously, we would like higher response rates and longer OS, but that combination is the promise of immunotherapy. Hopefully, this is just the beginning.
Are nivolumab combinations being explored in this setting?
There are a number of companies combining anti–PD-1 agents with radiotherapy and different chemotherapies in the neoadjuvant setting, the adjuvant setting, and in the locally advanced setting.