Robert L. Ferris, MD, PhD
Updated 2-year findings from the phase III CheckMate-141 trial showed a 32% reduction in the risk of death in patients with metastatic or recurrent squamous cell carcinoma of the head and neck treated with nivolumab (Opdivo) compared with investigator’s choice of chemotherapy.
During the 2018 AACR Annual Meeting, lead investigator Robert L. Ferris, MD, PhD, reported that the 2-year overall survival (OS) rate was 16.9% with nivolumab versus 6% in the control arm (cetuximab, methotrexate, or docetaxel). The median overall survival (OS) with nivolumab was 7.7 months compared with 5.1 months, respectively (HR, 0.68; 95% CI, 0.54-0.86).
This update confirms the benefit of anti–PD-1 therapy in head and neck cancer, and it showed that patients can benefit regardless of PD-L1 status, said Ferris. Although the OS was higher in those who express PD-L1 ≥1%, there was a 27% reduction in the risk of death for those who had PD-L1 expression on <1% of cells (HR, 0.73; 95% CI, 0.49-1.09). This is in comparison to a 45% reduction in the risk of death with nivolumab over investigator's choice of therapy in the PD-L1–positive group (HR, 0.55; 95% CI, 0.39-0.78).
In an interview with OncLive
during the meeting, Ferris, who is the director of University of Pittsburgh Medical Center Hillman Cancer Center, discussed the implications of these updated findings, adding that this trial confirms the hypothesis that head and neck cancer is an immune-responsive disease.
OncLive: What were the significant findings of this 2-year update?
The CheckMate-141 trial was a randomized phase III registrational study, which compared nivolumab with investigator's choice of chemotherapy. For a group of patients who have very poor prognosis, it was the first study to demonstrate that immunotherapy was clinically effective and better than the standard of care at the primary analysis. It was stopped early because of a positive signal at the interim data [analysis]. We are now showing, with long-term data, that the benefit persists and the OS is approximately triple of the investigator's choice of chemotherapy.
Interestingly, at the primary interim analysis, those expressing less than 1% of PD-L1 in the tumor had a relatively modest clinical benefit with a hazard ratio of 0.89, whereas for the entire trial, it was 0.70. Now with 2-year minimum follow-up, the hazard ratio has continued to improve for this group of patients who were PD-L1 negative. The hazard ratio at 1 year went from 0.89 to 0.83, and now at 2 years, it is 0.73—a [27%] reduction in risk of death, even for the population who was PD-L1 negative. In fact, the OS is basically the same for patients treated with nivolumab who were PD-L1 positive or negative. That is pretty impressive, and it justifies not using PD-L1 as a selection biomarker for nivolumab therapy in patients with head and neck cancer.
How do these updates impact the treatment of patients with head and neck cancer moving forward?
This [whole] trial has brought up some questions. First, who will benefit from nivolumab therapy? When patients progress within 6 months of platinum-based therapy, the only option we have is immunotherapy. However, we wanted to ask whether you could select patients by HPV status, because HPV causes approximately half of head and neck cancers. At 2 years, the benefit appears to be the same for HPV-positive patients and HPV-negative patents, which both had about a 40% reduction in risk of death.