Treatment with the PD-1 inhibitor nivolumab was active and tolerable across three doses for patients with metastatic renal cell carcinoma.
Robert J. Motzer, MD
Treatment with the PD-1 inhibitor nivolumab (Opdivo) was active and tolerable across three doses for patients with metastatic renal cell carcinoma (mRCC), according to results from a phase II study published in theJournal of Clinical Oncology.
In the study, 168 patients with clear-cell mRCC received intravenous nivolumab at 0.3 mg/kg (n = 60), 2 mg/kg (n = 54), or 10 mg/kg (54) once every 3 weeks. Those enrolled in the study had received prior therapy with a VEGF-targeted therapy. The primary outcome measure was progression-free survival (PFS), with overall survival (OS) and objective response rates (ORR) as secondary outcome measures.
"Seventy percent of patients had received more than one prior systemic regimen, including 40% who had received two or three prior antiangiogenic drugs and approximately one third who had received prior everolimus," the authors noted.
In the two larger dose arms, the median PFS was 4.0 and 4.3 months and the median OS was 25.5 and 24.7 months, in the 2 mg/kg and 10 mg/kg arms, respectively. Median survival outcomes were lower in the 0.3 mg/kg arm, with a median PFS of 2.7 months and a median OS of 18.2 months. The ORR was similar at 20%, 22%, and 20% in the 0.3-, 2-, and 10-mg/kg arms, respectively.
"ORR was similar by treatment arm, ranging from 20% to 22% and including patients with ongoing, durable objective responses," the authors wrote. "At data cutoff, 40% of the 35 objective responders were still responding ≥24 months from start of nivolumab therapy."
PD-L1 expression status was assessed, with a median PFS of 4.9 months in the PD-L1 ≥5% subgroup (positive) versus 2.9 months in the PD-L1 <5% subgroup (negative). The ORR was 31% in the PD-L1-positive group and 18% in the PD-L1-negative arm.
"Our data show that although response to treatment was higher in patients with greater PD-L1 expression (≥ 5%), those with lower PD-L1 expression (< 5%) also had meaningful responses," Motzer et al, explained. "These PD-L1 outcome data were assessed as an exploratory endpoint but are consistent with earlier published observations."
A majority of the patients enrolled in the study experienced an adverse event of any grade (73%), with 11% experiencing a grade 3/4 event. All-grade adverse events were similar across doses, at 75%, 67%, and 78% in the 0.3-, 2-, and 10-mg/kg groups, respectively. Grade 3/4 pneumonitis was not reported in the study.
Systemic corticosteroids were required for the managed of adverse events in more patients treated with the 10-mg/kg dose (33%) compared with the 0.3 (15%) and 2 mg/kg doses (19%).
"The frequency of treatment-related adverse events were similar across groups, and treatment-related adverse events were primarily low grade in severity," the authors wrote. "Cases of drug-related pneumonitis associated with fatal outcome were observed in the phase I trial in other tumor types, but no high-grade pneumonitis was observed in our trial."
"Findings from our dose-ranging study, coupled with analyses of safety and efficacy across tumor types from a large phase I study, support the selection of nivolumab 3 mg/kg intravenously every 2 weeks as the monotherapy dosing regimen for further study," Motzer et al, wrote.
A phase III trial is currently comparing treatment with nivolumab and everolimus using an OS primary endpoint in patients with mRCC who have been pretreated with antiangiogenic therapy (NCT01668784). Additionally, a phase III study is examining the combination of nivolumab and ipilimumab in comparison with single-agent sunitinib in previously untreated mRCC. The endpoint of this study is OS (NCT02231749).
Motzer RJ, Rini BI, McDermott DF, et al. Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial.J Clin Oncol. 2015;33(13):1430-1437.
George Discusses Potency of VEGF TKIs in Advanced Renal Cell Carcinoma
March 22nd 2024During a Case-Based Roundtable® event, Saby George, MD, discussed the case of a patient with clear cell renal cell carcinoma who progressed after left nephrectomy followed by treatment with axitinib plus pembrolizumab at recurrence.
Read More
Enhancing Precision in Immunotherapy: CD8 PET-Avidity in RCC
March 1st 2024In this episode of Emerging Experts, Peter Zang, MD, highlights research on baseline CD8 lymph node avidity with 89-Zr-crefmirlimab for the treatment of patients with metastatic renal cell carcinoma and response to immunotherapy.
Listen
Evolving Evidence Guides Treatment Selection for Favorable-Risk mRCC
March 6th 2024During a Targeted Oncology™ Case-Based Roundtable™ event, Rana McKay, MD, moderated a discussion on key takeaways from frontline combination trial data in patients with metastatic renal cell carcinoma. This is the second of 2 articles based on this event.
Read More
Beyond the First-Line: Economides on Advancing Therapies in RCC
February 1st 2024In our 4th episode of Emerging Experts, Minas P. Economides, MD, unveils the challenges and opportunities for renal cell carcinoma treatment, focusing on the lack of therapies available in the second-line setting.
Listen
Guideline Recommendation Favors Doublet Over Triplet Therapy in ccRCC
February 28th 2024New guideline favors doublet therapy over triplet for metastatic renal clear cell cancer due to lower toxicity. COSMIC-313 trial shows improved progression-free survival with triplet therapy but significant adverse events.
Read More
Risk Groups Vital to Interpreting Results of RCC Immunotherapy Trials
February 21st 2024During a Targeted Oncology™ Case-Based Roundtable™ event, Robert J. Motzer, MD, examined the impact of the CheckMate 214 and CheckMate 9ER trials of nivolumab/ipilimumab and nivolumab/cabozantinib in patients with advanced renal cell carcinoma. This is the first of 2 articles based on this event.
Read More