Lead Investigator Discusses Nivolumab Long-Term Survival Benefit in SCCHN

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).

OncLive: What were the significant findings of this 2-year update?

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.Ferris: 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.

How do these updates impact the treatment of patients with head and neck cancer moving forward?

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. 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.

What is the main message that you hope oncologists took away from these findings?

Are there any other trials with immunotherapy that look promising?

Because PD-L1 testing is used to select patients, we have demonstrated that patients, regardless of PD-L1 status, still benefit and the tolerability is better with about half the rate of grade 3/4 adverse events (AEs). We [also] built in quality-of-life assessments. Quality of life stabilized, or in some cases improved, with nivolumab therapy. It is an effective therapy that improves quality of life and it can be delivered with a low AE profile.It confirms that head and neck cancer is an immune-responsive disease. [Immunotherapy] is truly the fourth modality. We now have patients who have progressed on surgery, radiation, chemotherapy, and this suggests that immunotherapy is a new platform and paradigm for patients with head and neck cancer. It is very exciting, and we can use this to build on with combinations and hopefully get some biomarkers to figure out who would benefit more, and who needs a combination upfront. One of the tremendous benefits of the positive CheckMate-141 data, and other immunotherapy agents in head and neck cancer, is that there is a proliferation of clinical trials. There are combinations in recurrent disease, but also in locally advanced disease in patients who are getting chemotherapy and radiation. We are now adding immunotherapy agents such as nivolumab and other anti—PD-1 therapies to try and improve survival in the previously untreated population. Therefore, moving it into earlier stages of disease and in the recurrent metastatic setting, [plus the concept of] combinations is all very exciting for patients—and for clinicians who get to offer something unique for their patients.

Ferris RL, Blumenschein GR, Fayette J, et al. Nivolumab (Nivo) vs investigator’s choice (IC) in recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): 2-yr outcomes in the overall population and PD-L1 subgroups of CheckMate 141. In: Proceedings from the 2018 AACR Annual Meeting; April 14-18, 2018; Chicago, Illinois. Abstract CT116.