Nivolumab OS Benefit Sustained in Long-Term Follow-Up for SCCHN

Robert Ferris, MD, PhD

Treatment with nivolumab (Opdivo) reduced the risk of death by 32% compared with investigator’s choice of therapy for patients with metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN), according to updated findings with a minimum of 2 years of follow-up from the phase III CheckMate-141 study.

The median overall survival (OS) was 7.7 months (95% CI, 5.7-8.8) with nivolumab compared with 5.1 months (95% CI, 4.0-6.2) for investigator's choice of therapy (HR, 0.68; 95% CI, 0.54-0.86). The 2-year OS rate was 16.9% with nivolumab (95% CI, 12.4-22.0) versus 6% in the control arm (95% CI, 2.7-11.3). Safety data for the two arms remained consistent with longer follow-up.

"This was the first study to demonstrate that immunotherapy was clinically effective and better than the standard of care," lead investigator Robert L. Ferris, MD, PhD, director, UPMC Hillman Cancer Center, told OncLive. "We're now showing, with longer term data, that the benefit persists. The overall survival is approximately triple—3 times as much—as the investigator's choice of therapy."

In the phase III trial, 361 patients with cancer of the oral cavity, pharynx, or larynx were randomized in a 2:1 ratio to receive nivolumab (n = 240) or investigator's choice of therapy (n = 121), which consisted of cetuximab (12.4%), methotrexate (44.6%), or docetaxel (43%). Nivolumab was administered intravenously at 3 mg/kg every 2 weeks. Cetuximab was administered at 400 mg/m² for the first dose followed by 250 mg/m² weekly. Methotrexate was administered at 40 mg/m² weekly. Docetaxel was administered at 30 mg/m² weekly.

At baseline, the median age of patients in the trial was 60 years, and 31.3% were ≥65 years of age. Most patients were male (83%), Caucasian (83%), and had an ECOG PS of 1 (78.4%). More than half of patients (54.8%) received ≥2 prior systemic therapies, and over 90% had received prior radiation therapy. HPV status was known for 49.3% of patients, using p16 status, and PD-L1 expression was available for 72% of enrolled patients.

In data from CheckMate-141 that led to FDA approval for nivolumab in November 2016, the median OS was 7.5 months with the PD-1 inhibitor compared with 5.1 months with investigator's choice of therapy (HR, 0.70; 95% CI, 0.52-0.92; P = .0101). The objective response rate was 13.3% with nivolumab and 5.8% for investigator's choice. Progression-free survival was not improved at both the primary analysis (HR, 0.89; 95% CI, 0.70-1.10) and the long-term follow-up (HR, 0.87; 95% CI,0.68-1.11).

"Interestingly, whereas at the primary interim analysis the PD-L1—negatives had a relatively modest clinical benefit, now, with 2 years’ minimal follow-up, the hazard ratio has continued to improve for this group of patients who were PD-L1–negative," said Ferris. "This is a 27% reduction in death, even for the population who was PD-L1–negative."

"In fact, the overall survival is basically the same in patients treated with nivolumab who were PD-L1—positive or –negative," he continued. "It justifies not using PD-L1 as a selection biomarker for nivolumab therapy in head and neck cancer patients." Adding to this, Ferris noted that outcomes were also similar regardless of HPV status, highlighting the need for a better biomarker for patient selection.

Benefits in OS were accompanied by fewer adverse events (AEs) for patients treated with the PD-1 inhibitor. Overall, grade 3/4 treatment-related AEs were experienced by 15.3% of patients treated with nivolumab compared with 36.9% of those in the control arm.

“The tolerability is better. There is about half the rate of grade 3/4 adverse events," Ferris said. "We built in quality of life assessments. And, quality of life stabilized, or in some cases improved with nivolumab."

The next steps for research into the PD-1 inhibitors in SCCHN include investigations into localized disease and combination strategies, Ferris said.

A phase III study in the first-line setting is examining the combination of nivolumab and the IDO1 inhibitor BMS-986205 (NCT03386838). Additionally, another first-line phase III study is looking at nivolumab plus the CTLA-4 inhibitor ipilimumab (Yervoy) for recurrent/metastatic SCCHN (NCT02741570). In the localized setting, a phase III study is looking at nivolumab with or witout cisplatin with radiotherapy (NCT03349710).

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. Presented at: AACR Annual Meeting 2018; April 14-18, 2018; Chicago, Illinois. Abstract CT116.

<<< 2018 AACR Annual Meeting

In the long-term assessment, OS remained consistent for those with PD-L1—positive disease, with a slight improvement in outcomes in the PD-L1 –negative cohort, Ferris noted. In patients with SCCHN with PD-L1 expression ≥1% there was a 45% reduction in the risk of death with nivolumab over investigator's choice (HR, 0.55; 95% CI, 0.39-0.78). For those with PD-L1 expression on <1% of cells, the OS benefit was less pronounced, with a 27% reduction in the risk of death (HR, 0.73; 95% CI, 0.49-1.09).