A subgroup analysis of the CheckMate 141 phase III trial found that nivolumab achieved better overall survival (OS) and objective response rate (ORR) than investigator’s choice (IC) in a first-line setting among patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck who had received a platinum as primary therapy but whose disease had progressed within 6 months.
“This is a particularly interesting patient population because, historically, they are less likely to respond to chemotherapy, they have rapid progression, and a very poor outcome,” Maura L. Gillison, MD, PhD, of The Ohio State University, said. Dr. Gillison presented the findings in a Poster Session (Abstract 6019) on June 5.
The subgroup analysis was based on 78 patients (21.6% of the total study population), 52 of whom received nivolumab every 2 weeks and 26 of whom received weekly IC, which was either methotrexate, docetaxel, or cetuximab. The OS among patients in this subgroup who received nivolumab was 7.7 months (95% CI [3.1, 13.8]) compared with 3.3 months (95% CI [2.1, 6.4]) for those who received IC. The 12-month OS rates for nivolumab and IC were 39.2% and 15.4%, respectively, and the ORR was 19.2% for nivolumab and was 11.5% for IC. The grade 3 and 4 adverse event rates in this subgroup for nivolumab and IC were 27.5% and 32%, respectively.
“Patients treated [with nivolumab] in the first-line who have regressed within 6 months of their initial therapy that included platinum appear to derive the same benefit in terms of survival and response as the entire study population, and if anything, seem to have a slightly better benefit. Some physicians then might decide for a select group of patients that perhaps nivolumab should be their first-line [therapy] instead of alternative standard chemotherapies now, but that particular question is currently the subject of numerous ongoing clinical trials,” Dr. Gillison said.
Dr. Gillison also presented a minimum 11.4-month follow-up analysis of CheckMate 141 for the overall patient population in the study to update the previous 2.2-month follow-up findings. A total of 361 patients were randomly assigned 2:1 to receive nivolumab or IC, as in the subgroup of 21.6% of patients; the remainder of the patients, outside the subgroup, had platinum-refractory disease in the adjuvant setting.
In the entire patient population, nivolumab continued to demonstrate better OS and survival compared with IC at the later follow-up timepoint. The OS in the nivolumab group was 7.7 months (95% CI [5.7, 8.8]) compared with 5.1 months (95% CI [4.0, 6.2]) for the IC group. The 18-month OS rates for nivolumab and IC were 21.5% and 8.3%, respectively, and the ORR was 13.3% for nivolumab and was 5.8% for IC. The overall rates of grade 3 and 4 adverse events for nivolumab and IC were 15.3% and 36.0%, respectively.
“This confirms with longer follow-up the survival benefit of nivolumab [over chemotherapy] in a phase III trial among patients who are platinum refractory,” discussant Ranee Mehra, MD, of Johns Hopkins University, said. “We continue to await data from a first-line platinum-naive population.”
The progression-free survival (PFS), Dr. Mehra noted, was similar between the two arms in the CheckMate 141 trial: the median PFS was 2 months (95% CI [1.9, 2.1]) in the nivolumab group and was 2.3 months (95% CI [2.0, 3.1]) in the IC group. “This is confirming what we’ve seen in multiple studies, that PFS is not a surrogate of activity for PD-1 inhibitors in this disease,” Dr. Mehra said.
–Carina Storrs, PhD