After a median follow-up of 9.9 months, 38% of the trial participants experienced some degree of tumor shrinkage after receiving Opdivo in combination with Yervoy.
Combining Opdivo (nivolumab) and Yervoy (ipilimumab) resulted in some responses to therapy in a subset of patients with rare genitourinary malignancies, according to data from a multicenter trial published in Cancer.
“Collectively, … rare genitourinary malignancies are often excluded from clinical trials, and this leaves these patients with a dearth of options beyond experimental therapies,” the authors wrote. “Because of the challenges treating rare genitourinary cancers (including those with predominant variant histology), we pursued a multicenter, single arm, phase 2 study of (Opdivo) and (Yervoy) in those patients with bladder and upper tract carcinoma of variant histology (BUTCVH), adrenal tumors, prostate cancer of variant histology (PCVH; including squamous or neuroendocrine differentiation) penile carcinoma, or platinum refractory germ cell tumors.”
Patients with histologically confirmed advanced genitourinary malignancies were enrolled on the trial and separated into three cohorts:
From April 2018 to July 2019, 55 eligible patients (median age, 59 years) received four doses Opdivo at 3 mg/kg and Yervoy at 1 mg/kg every three weeks; after this they received 480 mg of Opdivo every four weeks until intolerable toxicity or withdrawal of consent. Cohort 1 comprised 19 patients and cohorts 2 and 3 comprised 18 patients, each.
Measuring objective response rate (the proportion of patients who achieved a complete or partial response to treatment) was the main goal of the study. After a median follow-up of 9.9 months, the objective response rate (ORR) was 37% in the BUTCVH cohort and 6% in the other two cohorts. Overall, 38% of the trial participants experienced some degree of tumor shrinkage, including 47% of patients in the BUTCVH cohort.
A median duration of response to therapy was not reached in those within the BUTCVH cohort who achieved a response. Of those in the BUTCVH cohort, 67% maintained a response to therapy for more than nine months.
All trial participants received at least one dose of the combination and slightly more than half (51%) received all four doses.
The researchers evaluated adverse events among all patients who received at least one dose of therapy. The most common treatment-related adverse events of any severity were elevated liver enzymes (38%), fatigue (36%), rashes (35%), diarrhea (24%), thyroid disorders (22%), itch (18%), elevated lipase (16%), pulmonary symptoms (15%), low sodium levels in the blood (11%), and joint pain (11%).
Three deaths, two of which were attributed to disease progression, occurred during the study.
“Our findings suggest that the combination of nivolumab and ipilimumab has efficacy in a subset of rare genitourinary malignancies. We observed differential responses between the cohorts of rare genitourinary malignancies, with the most robust objective responses seen in the BUTCVH cohort; this provides rationale for exploring the combination further in this subpopulation,” the authors concluded.
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