Opdivo (nivolumab) was approved by the U.S. Food and Drug Administration (FDA) for patients with metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN) following progression on platinum-based therapy.
The approval is based on the CheckMate-141 study, in which the median overall survival (OS) with Opdivo was 7.5 months compared with 5.1 months with investigator's choice. The objective response rate (ORR) was 13.3 percent with Opdivo and 5.8 percent for investigator's choice.
In the trial, 361 patients with cancer of the oral cavity, pharynx, or larynx were randomized in a 2:1 ratio to receive Opdivo (240 patients) or investigator's choice of cetuximab (12.4 percent), methotrexate (44.6 percent), or docetaxel (43 percent; 121 patients). Opdivo was administered intravenously at 3 mg/kg every two 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.
The median age of patients in the trial was 60 years, and 31.3 percent were 65 years of age or older. The majority of patients were male (83 percent), Caucasian (83 percent), and had an ECOG PS of 1 (78.4 percent). Most patients (54.8 percent) received at least two prior systemic therapies, and over 90 percent had received prior radiation therapy. HPV status was known for 49.3 percent of patients, using p16 status, and PD-L1 expression was available for 72 percent of enrolled patients.
The one-year OS rates were 36 percent with Opdivo compared with 16.6 percent for investigator’s choice. Similar improvements in survival were seen across demographic subgroups. The ORR in the Opdivo arm consisted of six complete responses (2.5 percent) and the stable disease (SD) rate was 22.9 percent. In the investigator's choice arm, one patient had a complete response and the SD rate was 35.5 percent.
The median progression-free survival (PFS) was two months with Opdivo versus 2.3 months with investigator's. The six-year PFS rates were 19.7 percent for Opdivo and 9.9 percent for investigator's choice of therapy.
Further analyses revealed distinct populations of patients who responded better to Opdivo monotherapy versus investigator's choice, specifically those with PD-L1–positive and HPV-positive SCCHN. Those with PD-L1 expression on 1 or more percent of cells experienced a median OS of 8.7 months with Opdivo compared with 4.6 months in the control arm. In the HPV-positive group, the median OS was 9.1 months with Opdivo compared with 4.4 months with investigator’s choice.
Those who tested negative for PD-L1 had a median OS of 5.7 months with Opdivo versus 5.8 months in the control arm. In the HPV-negative arm, the median OS with Opdivo was 7.5 versus 5.8 months.
Adverse events (AEs) were significantly less with Opdivo versus investigator's choice. There were two treatment-related deaths in the Opdivo arm related to pneumonitis and hypercalcemia. In the investigator's choice arm, there was one death related to lung infection.
Overall, grade 3/4 events were experienced by 13.1 percent of patients treated with Opdivo versus 35.1 percent for investigator’s choice. All-grade AEs were experienced by 58.9 percent of patients treated with Opdivo compared with 77.5 percent with investigator's choice. The most common grade 3/4 AEs with Opdivo were fatigue (2.1 percent), anemia (1.3 percent) and asthenia (0.4 percent). For investigator's choice, the most common grade 3/4 AEs were anemia (4.5 percent), alopecia (2.7 percent), fatigue (2.7 percent), diarrhea (1.8 percent), asthenia (1.8 percent) and mucosal inflammation (1.8 percent).
In April 2016, Opdivo was granted a breakthrough therapy designation as a treatment for patients with SCCHN. This designation was also based on findings from the CheckMate-141 study, which was stopped early in January 2016 after showing an improvement in OS.
Since its initial approval for patients with melanoma in 2014, Opdivo has received numerous additional indications. The agent is approved for patients with non–small cell lung cancer, renal cell carcinoma, and classical Hodgkin lymphoma, as well as for patients with melanoma as a single-agent and with the CTLA-4 inhibitor Yervoy (ipilimumab).