Marie Auvray1, Edouard Auclin2, Philippe Barthelemy3, Petri Bono4, Pirkko Kellokumpu-Lehtinen5, Marine Gross-Goupil6, Guillermo De Velasco7, Thomas Powles8, Guillaume Mouillet9, Yann-Alexandre Vano10, Gwenaëlle Gravis11, Loïc Mourey12, Franck Priou13, Frédéric Rolland14, Bernard Escudier1, Laurence Albiges15. 1. Medical Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France. 2. Gastrointestinal Oncology Department, European Georges Pompidou Hospital, Université René Descartes, Paris, France; Methodology and Quality of Life Unit in Oncology, University Hospital of Besançon, Besançon, France; Univ. Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, F-25000, Besançon, France. 3. Medical Oncology, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. 4. Comprehensive Cancer Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland. 5. Department of Oncology, Tampere University Hospital and University of Tampere, Tampere, Finland. 6. Oncology Department, Centre Hospitalier Universitaire, Bordeaux, Aquitaine, France. 7. Department of Medical Oncology, University Hospital 12 de Octubre, I + 12, Madrid, Spain. 8. Barts Cancer Institute, Queen Mary University of London, London, UK. 9. Department of Medical Oncology, University Hospital, Besançon, France. 10. Oncology Department, European Georges Pompidou Hospital, Université René Descartes, Paris, France. 11. Medical Oncology, Institut Paoli-Calmettes, Marseille, France. 12. Department of Oncology, Institut Claudius Regaud, IUCT-Oncopole, Toulouse, France. 13. Department of Oncology, Centre Hospitalier Départemental Les Oudairies, La Roche-sur-Yon, France. 14. Medical Oncology, Institut René Gauducheau, Saint Herblain, France. 15. Medical Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France. Electronic address: laurence.albiges@gustaveroussy.fr.
Abstract
BACKGROUND: Nivolumab-ipilimumab demonstrated a survival benefit over sunitinib in first-line setting for metastatic renal cell carcinomas (mRCCs) and is becoming a new standard of care for naïve patients with intermediate or poor risk prognosis (International mRCC Database Consortium). The efficacy of subsequent vascular endothelial growth factor receptor tyrosine kinase inhibitors (TKIs) after nivolumab-ipilimumab failure remains unclear. METHODS: Medical records of mRCC patients treated with nivolumab-ipilimumab, who received subsequent TKI, as part of Checkmate 214 study were reviewed in 13 institutions. Baseline characteristics, outcome data including progression-free survival (PFS), response, overall survival (OS) and toxicities were retrospectively collected. RESULTS: Overall 33 patients received subsequent TKI after nivolumab-ipilimumab failure. Median follow-up from start of subsequent TKI is 22 months (19-NR). Best response was assessed in 30 patients: 12 partial responses (36%), 13 stable diseases (39%) and five progressive diseases (15%). Median PFS from start of TKI was 8 months [5-13]. Median PFS with first-generation (sunitinib/pazopanib) and second-generation TKI (axitinib/cabozantinib) was 8 months [5-16] and 7 months (5-NA), respectively. PFS in second line was significantly longer in patients with a long first-line duration of response to the double immune checkpoint blockade (≥6 months) with 8 versus 5 months for short responder (<6 months) (p = 0.03). OS rate was 54% at 12 months. Toxicity was as expected: 42% developed at least one toxicity grade ≥3. CONCLUSION: This is the first report of outcomes with TKI, after first-line nivolumab-ipilimumab failure. Median PFS suggests a sustained benefit of TKI and supports trials investigating the optimal sequence.
BACKGROUND:Nivolumab-ipilimumab demonstrated a survival benefit over sunitinib in first-line setting for metastatic renal cell carcinomas (mRCCs) and is becoming a new standard of care for naïve patients with intermediate or poor risk prognosis (International mRCC Database Consortium). The efficacy of subsequent vascular endothelial growth factor receptor tyrosine kinase inhibitors (TKIs) after nivolumab-ipilimumab failure remains unclear. METHODS: Medical records of mRCC patients treated with nivolumab-ipilimumab, who received subsequent TKI, as part of Checkmate 214 study were reviewed in 13 institutions. Baseline characteristics, outcome data including progression-free survival (PFS), response, overall survival (OS) and toxicities were retrospectively collected. RESULTS: Overall 33 patients received subsequent TKI after nivolumab-ipilimumab failure. Median follow-up from start of subsequent TKI is 22 months (19-NR). Best response was assessed in 30 patients: 12 partial responses (36%), 13 stable diseases (39%) and five progressive diseases (15%). Median PFS from start of TKI was 8 months [5-13]. Median PFS with first-generation (sunitinib/pazopanib) and second-generation TKI (axitinib/cabozantinib) was 8 months [5-16] and 7 months (5-NA), respectively. PFS in second line was significantly longer in patients with a long first-line duration of response to the double immune checkpoint blockade (≥6 months) with 8 versus 5 months for short responder (<6 months) (p = 0.03). OS rate was 54% at 12 months. Toxicity was as expected: 42% developed at least one toxicity grade ≥3. CONCLUSION: This is the first report of outcomes with TKI, after first-line nivolumab-ipilimumab failure. Median PFS suggests a sustained benefit of TKI and supports trials investigating the optimal sequence.
Authors: A Y Shah; R R Kotecha; E A Lemke; A Chandramohan; J L Chaim; P Msaouel; L Xiao; J Gao; M T Campbell; A J Zurita; J Wang; P G Corn; E Jonasch; R J Motzer; P Sharma; M H Voss; N M Tannir Journal: Eur J Cancer Date: 2019-05-07 Impact factor: 9.162
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