The EMA’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval of nivolumab (Opdivo) for the treatment of patients with squamous cell cancer of the head and neck (SCCHN) following progression on platinum-based therapy, according to Bristol-Myers Squibb (BMS), the manufacturer of the PD-1 inhibitor.
The approval is based on the CheckMate-141 study, in which the median overall survival (OS) with nivolumab was 7.5 months compared with 5.1 months with investigator's choice (HR, 0.70; 95% CI, 0.52-0.92; P
= .0101). The objective response rates (ORR) were 13.3% versus 5.8%, respectively.
The positive opinion will now be reviewed by the European Commission (EC) and a final approval decision for use in the European Union (EU) is expected in about 2 months. In the United States, nivolumab was previously approved by the FDA for SCCHN in November 2016.
“Nearly half of all patients with squamous cell cancer of the head and neck relapse within 2 years of treatment and limited advancements have been made in the last 10 years, underscoring the critical need for new treatment options for patients affected by this devastating illness,” Emmanuel Blin, senior vice president and chief strategy officer, BMS, said in a statement.
“We are very pleased that the CHMP has recommended the approval of Opdivo for adults with squamous cell cancer of the head and neck who have progressed on or after platinum-based therapy and look forward to working with the EC as they review this treatment as a potential option for patients in the EU,” added Blin.
In the 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 cetuximab (12.4%), methotrexate (44.6%), or docetaxel (43%; N = 121). 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
The median age of patients in the trial was 60 years, and 31.3% were ≥65 years of age. The majority of patients were male (83%), Caucasian (83%), and had an ECOG PS of 1 (78.4%). Most 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.
The 1-year OS rates were 36% with nivolumab (95% CI, 28.5-43.4) compared with 16.6% for investigator’s choice (95% CI, 8.6-26.8). Similar improvements in survival were seen across demographic subgroups. The ORR in the nivolumab arm consisted of 6 complete responses (2.5%) and the stable disease (SD) rate was 22.9%. In the investigator's choice arm, 1 patient had a complete response and the SD rate was 35.5%.
The median progression-free survival (PFS) was 2 months with nivolumab versus 2.3 months with investigator's choice (HR, 0.89; 95% CI, 0.70-1.10; P
= .3236). The 6-year PFS rates were 19.7% for nivolumab and 9.9% for investigator's choice of therapy.
Further analyses revealed distinct populations of patients who responded better to nivolumab monotherapy versus investigator's choice, specifically those with PD-L1–positive and HPV-positive SCCHN. Those with PD-L1 expression on ≥1% of cells experienced a median OS of 8.7 months with nivolumab compared with 4.6 months in the control arm (HR, 0.55; 95% CI, 0.36-0.83). In the HPV-positive group, the median OS was 9.1 months with nivolumab compared with 4.4 months with investigator’s choice (HR, 0.56; 95% CI, 0.32-0.99).
Those who tested negative for PD-L1 had a median OS of 5.7 months with nivolumab versus 5.8 months in the control arm (HR, 0.89; 95% CI, 0.54-1.45). In the HPV-negative arm, the median OS with nivolumab was 7.5 versus 5.8 months (HR, 0.73; 95% CI, 0.42-1.25).
Adverse events (AEs) were significantly less with nivolumab versus investigator's choice. There were 2 treatment-related deaths in the nivolumab arm related to pneumonitis and hypercalcemia. In the investigator's choice arm, there was 1 death related to lung infection.
Overall, grade 3/4 events were experienced by 13.1% of patients treated with nivolumab versus 35.1% for investigator’s choice. All-grade AEs were experienced by 58.9% of patients treated with nivolumab compared with 77.5% with investigator's choice. The most common grade 3/4 AEs with nivolumab were fatigue (2.1%), anemia (1.3%), and asthenia (0.4%). For investigator's choice, the most common grade 3/4 AEs were anemia (4.5%), alopecia (2.7%), fatigue (2.7%), diarrhea (1.8%), asthenia (1.8%), and mucosal inflammation (1.8%).
Ferris RL, Blumenschein GR, Fayette J, et al. Further evaluations of nivolumab (nivo) versus investigator’s choice (IC) chemotherapy for recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): CheckMate 141. J Clin Oncol. 2016;34 (suppl; abstr 6009).