Nivolumab, a programmed death 1 inhibitor, has been approved as second-line treatment for advanced renal cell carcinoma (RCC) in Europe since 2016. We investigated the toxicity and efficacy of nivolumab as well as potential predictive biomarkers in the Dutch population.
This was a retrospective, multicenter study of the Dutch national registry of nivolumab for the treatment of advanced RCC. The main outcome parameters included toxicity, objective response rate (ORR), overall survival (OS), progression-free survival (PFS), time to progression (TTP), and time to treatment failure (TTF). In addition, potential predictive and prognostic biomarkers for outcomes were evaluated.
Data on 264 patients were available, of whom 42% were International Metastatic RCC Database Consortium (IMDC) poor risk at start of nivolumab, 16% had ≥ 3 lines of previous therapy, 7% had non-clear-cell RCC, 11% had brain metastases, and 20% were previously treated with everolimus. Grade 3/4 immune-related adverse events occurred in 15% of patients. The median OS was 18.7 months (95% confidence interval, 13.7-23.7 months). Progression occurred in 170 (64.4%) of 264 patients, with a 6-and 12-months TTP of 49.8% and 31.1%, respectively. The ORR was 18.6% (49 of 264; 95% confidence interval, 14%-23%). Elevated baseline lymphocytes were associated with improved PFS (P = .038) and elevated baseline lactate dehydrogenase with poor OS, PFS, and TTF (P = .000). On-treatment increase in eosinophils by week 8 predicted improved OS (P = .003), PFS (P = .000), and TTF (P = .014), whereas a decrease of neutrophils was associated with significantly better TTF (P = .023).
The toxicity and efficacy of nivolumab for metastatic RCC after previous lines of therapy are comparable with the results in the pivotal phase III trial and other real-world data. On-treatment increase in eosinophil count is a potential biomarker for efficacy and warrants further investigation.
Clinical genitourinary cancer. 2020 Oct 14 [Epub ahead of print]
Saskia Lisa Verhaart, Yasmin Abu-Ghanem, Sasja F Mulder, Sjoukje Oosting, Astrid Van Der Veldt, Susanne Osanto, Maureen J B Aarts, Danny Houtsma, Frank P J Peters, Gerard Groenewegen, Carla M L Van Herpen, Loes M Pronk, Metin Tascilar, Paul Hamberg, Maartje Los, Gerard Vreugdenhil, Marco Polee, Albert J Ten Tije, John B A G Haanen, Axel Bex, Alfonsus J van den Eertwegh
Specialist Centre for Kidney Cancer, Royal Free London NHS Foundation Trust, London, United Kingdom., Department of Medical Oncology, Amsterdam UMC, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands., Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands., Department of Medical Oncology, University Medical Center Groningen, Groningen, The Netherlands., Department of Medical Oncology, Erasmus Medical Center-Cancer Institute, Rotterdam, The Netherlands., Department of Medical Oncology, Leids University Medical Center, Leiden, The Netherlands., Department of Medical Oncology, Maastricht University Medical Center, Maastricht, The Netherlands., Department of Medical Oncology, HAGA Hospital, The Hague, The Netherlands., Department of Medical Oncology, Zuyderland Hospital, Sittard - Geleen, The Netherlands., Department of Medical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands., Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Department of Medical Oncology, Isala Clinics, Zwolle, The Netherlands., Department of Medical Oncology, Franciscus Gasthuis and Vllietland, Rotterdam, The Netherlands., Department of Medical Oncology, St. Antonius Hospital, Nieuwegein, The Netherlands., Department of Medical Oncology, Máxima Medical Center, Eindhoven, The Netherlands., Department of Medical Oncology, Medical Center Leeuwarden, Leeuwarden, The Netherlands., Department of Medical Oncology, Amphia Hospital, Breda, The Netherlands., Department of Medical Oncology, Amsterdam UMC, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands; Division of Surgery and Interventional Science, University College London, London, United Kingdom; Department of Urology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. Electronic address: .