Clinical Benefit Seen With First-Line Nivolumab Plus Ipilimumab for R/M HNSCC With PD-L1 CPS ≥1 or ≥20

Patients with recurrent/metastatic head and neck squamous cell carcinoma and a PD-L1 combined positive score of 1 or more and 20 or more experienced a clinical benefit with first-line nivolumab plus ipilimumab compared with the EXTREME regimen.

Although the first-line combination of nivolumab (Opdivo) plus ipilimumab (Yervoy) did not significantly improve overall survival (OS) compared with the EXTREME regimen of cetuximab (Erbitux), cisplatin/carboplatin, fluorouracil for patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), clinical benefit was observed with the combination for patients with PD-L1 combined positive score (CPS) of 1 or more or 20 or more, according to results from the phase 3 CheckMate-651 trial (NCT02741570).

Findings from the trial, which were presented at the 2021 European Society for Medical Oncology Congress, indicated that the median OS for all randomized patients in the nivolumab plus ipilimumab group was 13.9 months (95% CI, 12.1-15.8) compared with 13.5 months (95% CI, 12.6-15.2) in the EXTREME group (HR, 0.95; 95% CI, 0.80-1.13; P = .4951). Median OS for patients with PD-L1 CPS of 20 or more was 17.6 months (95% CI, 13.8-22.0) and 14.6 months (95% CI, 12.3-16.0) in the nivolumab plus ipilimumab and EXTREME groups, respectively (HR, 0.78; 95% CI, 0.59-1.03; P = .0469). Additionally, the median OS among those with a PD-L1 CPS of 1 or more was 15.7 months (95% CI, 13.7-18.8) vs 13.2 months (95% CI, 11.1-14.6) in the EXTREME arm.

“Patients with recurrent/metastatic [HNSCC] have poor prognosis and notable morbidity, with deterioration of quality of life,” the investigators wrote. “Nivolumab and ipilimumab have distinct but complementary mechanisms of action, and have shown survival benefit and durable responses in several solid tumors.”

Eligible patients needed to have recurrent/metastatic HNSCC of the oral cavity, oropharynx, hypopharynx, or larynx. Other eligibility criteria included no prior treatment for recurrent/metastatic disease and an ECOG performance status of 0 or 1. Patients were allowed to undergo treatment with prior chemotherapy for locally advanced disease if they were progression-free at least 6 months after treatment.

A total of 947 patients were randomized 1:1 to receive either the nivolumab plus ipilimumab (n = 472) or the EXTREME regimen (n = 475). The nivolumab plus ipilimumab group received nivolumab at 3 mg/kg once every 2 weeks plus ipilimumab at 1 mg/kg once every 6 weeks. The EXTREME regimen featured an initial cetuximab dose of 400 mg/m2 once followed by cetuximab at 250 mg/m2 once weekly plus cisplatin at 100 mg/m2 or carboplatin area under the curve 5 on day 1. Additionally, fluorouracil was administered at a dose of 1000 mg/m2 per day for 4 days over 6 cycles. Cetuximab maintenance therapy was then administered at 250 mg/m2 once weekly.

The primary end points of this research were OS in all randomized patients and OS in patients with a PD-L1 CPS of 20 or more. Focal secondary end points were OS in patients with PD-L1 CPS of 1 or more, progression-free survival by blinded independent central review, overall response rate (ORR), and duration of response (DOR). Key exploratory end points included PFS and ORR/DOR in patients with PD-L1 CPS of 1 or more, patient-reported outcomes, and safety.

The median age for patients in the nivolumab plus ipilimumab group was 61 years (range, 24-86) and 62 years (range, 29-86) for patients in the EXTREME group. Males accounted for 80% and 84% of the patient populations in the nivolumab plus ipilimumab and EXTREME groups, respectively, with metastatic disease observed in 39% and 40% of the 2 respective cohorts.

For the analysis of all randomized patients, the median PFS was 3.3 months (95% CI, 2.8-4.2) for patients in the nivolumab plus ipilimumab group and 6.7 months (95% CI, 5.8-7.0) for patients in the EXTREME group (HR, 1.41; 95% CI, 1.21-1.65). The ORR was 24% and 37%, with complete responses seen in 7% and 5% of patients in the nivolumab plus ipilimumab and EXTREME groups, respectively. Additionally, the median DOR was 16.6 months (95% CI, 9.7-29.4) and 5.9 months (95% CI, 5.5-7.0) in both groups, respectively.

In the efficacy analyses for patients with PD-L1 CPS of 20 or more, the median PFS was 5.4 months (95% CI, 3.1-6.9) in the nivolumab plus ipilimumab group and 7.0 months (95% CI, 5.6-8.7) in the EXTREME group (HR, 1.02; 95% CI, 0.78-1.33). Moreover, patients in the nivolumab plus ipilimumab group had an ORR of 34% vs 36% in the EXTREME group, with complete responses seen in 12% and 7% of patients, respectively. The median DOR was 32.6 months (95% CI, 12.1–not reached) and 7.0 months (95% CI, 5.7-10.1), respectively.

Investigators also reported that patients with a PD-L1 CPS of 1 or more experienced a median PFS of 4.2 months (95% CI, 2.9-5.4) after being treated with nivolumab plus ipilimumab vs 6.1 months (95% CI, 5.6-7.0) in the EXTREME cohort (HR, 1.23; 95% CI, 1.03-1.47). Additionally, those in the experimental cohort had an ORR of 28% vs 36% in the control group. Patients who received nivolumab/ipilimumab had a median DOR of 18.3 months (95% CI, 10.9-32.6) compared with 6.0 months (95% CI, 5.6-7.6) in the EXTREME cohort.

A total of 72% of patients in the nivolumab plus ipilimumab group and 98% of patients in the EXTREME group experienced treatment-related adverse effects (TRAEs) of any grade, with 28% and 71% experiencing grade 3/4 TRAEs, respectively. Serious TRAEs of any grade were reported in 16% and 28% of patients, with grade 3/4 TRAES observed in 12% and 24% of patients, respectively.

Reference

Argiris A, Harrington K, Tahara M, et al. Nivolumab + ipilimumab vs EXTREME regimen as first-line treatment for recurrent/metastatic squamous cell carcinoma of the head and neck: final results of CheckMate 651. Presented at: 2021 ESMO Congress; September 16-21, 2021; Virtual. Accessed October 14, 2021. Abstract LBA36