Retrospective analyses of data collected in a real-world study provide assurance about using nivolumab (Opdivo) to treat elderly patients with metastatic renal cell carcinoma who have failed previous therapy.
Retrospective analyses of data collected in a real-world study provide assurance about using nivolumab (Opdivo) to treat elderly patients with metastatic renal cell carcinoma (mRCC) who have failed previous therapy.
The recently published research (PLoS One 2018;13:e0199642) was conducted recognizing that while approximately one-half of patients newly diagnosed with RCC are >65 years of age, there is a paucity of information about the activity of nivolumab in older patients. To provide insight about the efficacy and safety of nivolumab in older patients, the study analyzed data from the Italian cohort of the nivolumab Expanded Access Program (EAP) that provided the immune checkpoint inhibitor to patients with mRCC whose disease had progressed despite treatment with other therapies considered standard of care. The research was conducted by Maria Giuseppa Vitale, MD, of Azienda Ospedaliera Universitaria di Modena, Modena, Italy, and co-authors.
Of 389 patients enrolled in the EAP across 95 centers in Italy, 125 (32%) were elderly (age ≥70 years) and 70 patients (18%) were considered “very elderly” (age ≥75 years). The results of the analyses showed that the efficacy of nivolumab in the elderly subgroup of the Italian EAP cohort was similar to that observed in the overall EAP population and in the pivotal, phase III CheckMate-025 trial, which compared nivolumab to everolimus (Afinitor) as treatment for mRCC following prior antiangiogenic-based therapy. Adverse events in elderly patients treated with nivolumab in the EAP cohort were also comparable to those seen in the overall EAP population and to those previously reported.
Alexander Kutikov, MD, of Fox Chase Cancer Center, Philadelphia, noted, “Nivolumab in combination with ipilimumab (Yervoy) is currently one of the first-line treatments for Stage IV kidney cancer. Yet, over the years, many patients received and are now progressing through VEGF targeted therapy. For these patients, second-line nivolumab monotherapy is an option.”
“The study published in PLoS One reports safety and efficacy data on nivolumab as monotherapy without ipilimumab in patients who received and progressed through previous targeted therapy. Although a large portion were older than age 70, the vast majority had excellent performance status. This report again underscores that in appropriately-selected groups, age by itself fails to be a predictor of adverse events or treatment failure. This is important since >50% of patients who are diagnosed with RCC are over 65 years of age at presentation,” said Dr. Kutikov, who was not involved with the study.
Patients were eligible for enrollment in the EAP if they were ≥18 years of age, had histologically confirmed advanced or metastatic RCC with a clear-cell component, and had received at least one prior therapy for their advanced/metastatic disease. They received nivolumab, 3 mg/kg by intravenous infusion every 2 weeks for up to 24 months or until unacceptable toxicity, clear disease progression, or withdrawal of informed consent, although the protocol included defined circumstances allowing for continued treatment despite progression.
Within the subgroup of elderly patients, the median age was 75 years, 75% were male, 92% had an ECOG performance status of 0 or 1, and lung was the most common site of metastasis (73%).
Continue to the next page for more.During a median follow-up of 11.9 months, the objective response rate was 23% for the overall EAP cohort and 27% and 28% in the elderly and very elderly subgroups, respectively. The rates of stable disease in the overall, elderly, and very elderly groups were 32%, 35%, and 34%, respectively.
Overall survival rates were also numerically higher in the older cohorts compared with the overall population; for the entire cohort and the ≥70 years and ≥75 years subgroups, 12-month overall survival rates were 64.1%, 77.8%, and 77.7%, respectively.
The incidence of any treatment-related adverse event was slightly higher in the elderly and very elderly patients than in the overall Italian EAP population (37% and 40% vs. 33%). In particular, fatigue was more common in the elderly and very elderly subgroups than in the overall population (17% and 19% vs. 13%). The rates of Grade 3 or 4 treatment-related adverse events in the two older age groups, however, were lower than in the overall cohort (5% and 4% vs. 7%); rates of Grade 3/4 fatigue in the elderly, very elderly, and overall groups were 3%, 1%, and 2%, respectively. Rates of discontinuation due to a treatment-related adverse event were 8% in both the overall cohort and elderly subgroup and 12% in the very elderly patients.
The study’s authors received honoraria for an advisory role and/or grants/reimbursements for participation in scientific events from Bristol-Myers Squibb. Dr. Kutikov has been a speaker for Pfizer.