The efficacy of nivolumab, as investigated in an interim analysis of the NORA study was confirmed as treatment of patients with advanced renal cell carcinoma who received 2 more prior lines of therapy.
The efficacy of nivolumab (Opdivo) plus ipilimumab, as investigated in an interim analysis of the NORA study (NCT02940639), was confirmed as treatment of patients with advanced renal cell carcinoma (RCC) who received 2 more prior lines of therapy after the combination demonstrated comparable overall survival (OS) results to those observed in the phase 3 CheckMate 025 study (NCT01668784).
NORA is a prospective, observational, multicenter, non-interventional study being conducted in Germany. During the 35th European Association of Urology Virtual Annual Congress, Marc-Oliver Grimm, MD, presented the interim analysis results, which came from patients treated with nivolumab or nivolumab plus ipilimumab (Yervoy) in the real-world setting.
Of the 232 patients enrolled in the NORA study monotherapy population, the median age was 72 years (range, 44-86), and of those patients, 78 (34%) were aged 65 years or younger and 154 (66%) were aged 65 years or younger. The majority of patients were male (72%). The Karnofsky performance scores calculated at baseline were below 70 in 7% of patients, 70 in 8%, 80 in 27%, 90 in 23%, and 100 in 19%. The Memorial Sloan Kettering Cancer Center (MSKCC) risk scores were favorable for 16% of patients, intermediate for 58%, and poor for 30% of patients. The International Metastatic RCC Database Consortium (IDMC) risk score was favorable for 15% of subjects, intermediate for 58%, and poor for 17%. Patient characteristics in the NORA study were similar to those in CheckMate 025 with exceptions of age and age range.
Disease characteristics showed clear-cell RCC in 83% of the monotherapy population and non-clear cell RCC in 17%. The age at primary diagnosis for most patients (51.5%) was 65 years or younger. The duration of disease at baseline was a mean of 65 months (range, 2-363). The majority of patients in the single-agent cohort (77%) had 1 prior line of therapy, but 23% had 2 or more prior lines of therapy. The sites of metastasis observed at baseline were lung (71%), bone (32%), liver (27%), adrenal (18%), brain (5%), and other (42%). Eighty-six percent of patients underwent a nephrectomy prior to the study.
The median OS for patients treated with nivolumab alone was 26.9 months (95% CI, 16.7-not evaluable [NE]), which is similar to the median OS of 25.8 months (95% CI, 22.2-29.8) observed in CheckMate 025.
There were 62 patients who received the combination of nivolumab and ipilimumab who had a median age of 64 years (range, 44-85), and the majority of patients were male (68%). The Karnofsky performance score for this cohort was at least 70 in 92% of patients, the IMDC risk score was intermediate in 75% and poor in 23%. The MSKCC risk score was intermediate in 88% of the cohort and poor in 11% of the cohort. No patients who received nivolumab plus ipilimumab at front-line therapy had a favorable IMDC or MSKCC risk score. In terms of histologic subtype, 81% of patients had clear cell RCC and 19% had non-clear cell RCC. Thirty percent of patients in the combination cohort had a nephrectomy prior to study treatment.
Among patients aged 75 years or older who received nivolumab as second-line therapy, the median OS was NE (95% CI, 12.4-NE). Patients with bone metastases who were given nivolumab in the second-line setting had a median OS of 21.3 months (95% CI, 10.5-NE).
Partial response (PR) was the best level of response observed in the trial, which occurred in 63 patients (27%). There were 71 patients (30.5%) who had stable disease following treatment with nivolumab plus ipilimumab and 51 patients (21.9%) who had progressive disease. Response data are not yet available for 48 patients from the interim analysis.
The safety analysis showed that treatment-related adverse events (TRAEs) occurred in 44.8% of patients who received nivolumab as second-line therapy, and of those patients, 14.2% had more than 1 grade 3 to 5 TRAE. One grade 3-5 TRAE led to death caused partially by hepatobiliary failure.
In the group that received the combination of nivolumab and ipilimumab as frontline therapy, 24 out of 62 patients experienced TRAEs. Of those patients, 45.8% experienced more than 1 grade 3/4 TRAEs. However, no grade 5 TRAEs were observed with the combination.
The most common grade 3 TRAEs observed in the study included general disorders and administration site conditions (2.2%), investigations (2.2%), and neoplasms benign, malignant, and unspecified (2.2%).
The safety data were consistent with prior pivotal studies in advanced RCC, including the Checkmate 025 and CheckMate 214 (NCT02231749) trials. Looking ahead, Grimm considers the preliminary results from the combination of nivolumab plus ipilimumab to show promise for the treatment of patients with advanced RCC who are 75 years of age or older and have bone metastases.
Grimm MO, Grunwald V, Heyde VD, et al. Real world data on the use of nivolumab and ipilimumab combination therapy or nivolumab monotherapy in the treatment of renal cell carcinoma: Interim results from the non-interventional study (NIS) NORA. Presented at: 35th Annual European Association of Urology Congress; July 20-26, 2020; Virtual. Poster 722.