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Subcutaneous vs Intravenous Nivolumab for Renal Cell Carcinoma
TAKE-HOME MESSAGE
- This phase III noninferiority trial compared the use of subcutaneous nivolumab with that of intravenous nivolumab in patients with renal cell carcinoma. The results showed that subcutaneous nivolumab was noninferior to intravenous nivolumab based on pharmacokinetics and the objective response rate. The safety profile was consistent between the arms, and no new safety concerns were reported with subcutaneous nivolumab.
- The study supports subcutaneous nivolumab as an option for patients with renal cell carcinoma to reduce the treatment burden and improve healthcare efficiency, even across solid tumors.
abstract
This abstract is available on the publisher's site.
Access this abstract now Full Text Available for ClinicalKey SubscribersBACKGROUND
The evolving oncology treatment paradigm has created an unmet need for administration options that improve patient experiences and healthcare efficiencies.
PATIENTS AND METHODS
CheckMate 67T (NCT04810078) was a phase 3, open-label, multicenter, noninferiority trial in which patients with advanced/metastatic clear cell renal cell carcinoma were randomized to subcutaneous nivolumab (1200 mg every 4 weeks; coformulated with recombinant human hyaluronidase PH20 20,000 units) or intravenous nivolumab (3 mg/kg every 2 weeks). Primary objective was to assess the noninferiority of subcutaneous versus intravenous nivolumab by coprimary endpoints determined from a population pharmacokinetics analysis (time-averaged serum concentration over the first 28 days [Cavgd28], and minimum steady-state serum concentration [Cminss]; noninferiority threshold: lower boundary of 90% confidence interval (CI) of the geometric mean ratios [GMR] ≥0.8). Objective response rate (ORR) was a key secondary endpoint powered for noninferiority (noninferiority threshold: lower boundary of 95% CI of relative risk of ORR [subcutaneous versus intravenous nivolumab] ≥0.60).
RESULTS
Overall, 495 patients were randomized. Relative exposure in the subcutaneous versus intravenous arm reported by the GMR of Cavgd28 and Cminss was 2.098 (90% CI, 2.001-2.200) and 1.774 (90% CI, 1.633-1.927), respectively. After 8 months minimum follow-up, ORR was 24.2% with subcutaneous nivolumab (95% CI, 19.0-30.0) versus 18.2% with intravenous nivolumab (95% CI, 13.6-23.6; relative risk: 1.33 [95% CI, 0.94-1.87]). Coprimary endpoints and ORR met noninferiority thresholds. Additional efficacy and safety measures were similar.
CONCLUSION
Subcutaneous nivolumab was noninferior to intravenous nivolumab based on pharmacokinetics and ORR. No new safety signals were observed.
Additional Info
Disclosure statements are available on the authors' profiles:
Subcutaneous versus intravenous nivolumab for renal cell carcinoma
Ann. Oncol 2024 Sep 15;[EPub Ahead of Print], L Albiges, MT Bourlon, M Chacón, HJ Cutuli, YAL Chuken, B Żurawski, JM Mota, I Magri, M Burotto, M Luz, J de Menezes, EPY Ruiz, S Fu, M Richardet, BP Valderrama, M Maruzzo, S Bracarda, M Breckenridge, HE Vezina, D Rathod, Z Yu, Y Zhao, M Dixon, D Perumal, S GeorgeFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Renal Cell Carcinoma Center of Excellence
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Albiges et al present us with the results of the CheckMate 67T study. This was a phase III, open-label, multicenter, noninferiority trial in which patients with advanced/metastatic clear cell renal cell carcinoma were randomized to subcutaneous nivolumab (1200 mg every 4 weeks, coformulated with recombinant human hyaluronidase PH20 20,000 units) or intravenous nivolumab (3 mg/kg every 2 weeks).
Why is this important and relevant to any oncology clinic? Well, there is still a large dogma on a preference for intravenous administration of immune checkpoint therapy in most parts of the world. However, subcutaneous application can clearly reduce the burden of immunotherapy on the resources available to healthcare systems, as well as potentially allow for more patient-oriented administration.
The co-primary endpoints of the CheckMate 67T study were the time-averaged serum concentration over the first 28 days and the minimum steady-state serum concentration, as determined using a population pharmacokinetics analysis. It can be debated whether this is the appropriate endpoint for noninferiority rather than "hard" clinical endpoints, such as the overall response rate (ORR), progression-free survival, and overall survival. ORR was a key secondary (powered) endpoint.
The authors found that the subcutaneous concentrations were higher than the intravenous concentrations. Furthermore, the ORR was also higher at 24.2% versus 18.2%. Thus, it was concluded that subcutaneous administration was noninferior to intravenous administration.
One issue that is never mentioned is that there is often a financial incentive to continue with the intravenous administration of drugs, as this has a higher remuneration in most (private) health systems. However, this should not be a valid reason to continue this practice.
This study clearly shows that we should rethink any oncology practice and consider saying goodbye to our old dogmas.