A phase II trial of TKI induction followed by a randomized comparison between nivolumab or TKI continuation in renal cell carcinoma (NIVOSWITCH)

Date 30 September 2019
Event ESMO 2019 Congress
Session Poster Display session 3
Topics Renal Cell Cancer
Presenter Viktor Grünwald
Citation Annals of Oncology (2019) 30 (suppl_5): v356-v402. 10.1093/annonc/mdz249
Authors V. Grünwald1, C. Grüllich2, P. Ivanyi3, M. Wirth4, P. Staib5, M. Schostak6, P. Dargatz7, L. Müller8, M. Metz9, L. Bergmann10, M.K. Welslau11, P. Schütt12, M. Rafiyan13, E. Hellmis14, A. Hinke15, J. Meiler16, T. Kretz17, W.C. Loidl18, A. Flörcken19, T. Steiner20
  • 1Clinic For Cancer Research And Clinic For Urology, University Hospital Essen Westdeutsches Tumorzentrum, 45122 - Essen/DE
  • 2Medizinische Onkologie, Nationales Zentrum für Tumorerkrankungen (NCT), 69120 - Heidelberg/DE
  • 3Klinik Für Hämatologie, Hämostaseologie Und Onkologie, Hannover Medical School, 30625 - Hannover/DE
  • 4Klinik Und Poliklinik Für Urologie, Uniklinikum Dresden, 01307 - Dresden/DE
  • 5Klinik Für Hämatologie/onkologie, St. Antonius Hospital, 52249 - Eschweiler/DE
  • 6Urologischen Klinik, University Hospital Magdeburg, 39120 - Magdeburg/DE
  • 7Klinik Für Hämatologie/onkologie, Johannes Wesling Klinikum Minden, Minden/DE
  • 8Onkologie Leer, Studienzentrum Unter Ems, Leer/DE
  • 9Hämatologie/onkologie, OSP Göttingen, Göttingen/DE
  • 10Medical Clinic Ii, Universitätsklinikum Frankfurt, 60590 - Frankfurt am Main/DE
  • 11Onkologie, Klinikum Aschaffenburg, 63739 - Aschaffenburg/DE
  • 12Onkologische Schwerpunktpraxis, Onkologie Gütersloh, Gütersloh/DE
  • 13Klinik Für Onkologie Und Hämatologie, Krankenhaus Nordwest, 60488 - Frankfurt am Main/DE
  • 14Praxis Walsum, Urologicum Duisburg, Duisburg/DE
  • 15Hematology And Oncology, CCRC, 40595 - Düsseldorf/DE
  • 16Mvz Onkologie, Klinik Dr. Hancken, 21680 - Stade/DE
  • 17Onkologischer Schwerpunkt Und Studienzentrum, Urologische Gemeinschaftspraxis Heinsberg, Heinsberg/DE
  • 18Abteilung Für Urologie Und Andrologie, Ordensklinikum Linz, 4010 - Linz/AT
  • 19Hematology, Oncology And Tumor Immunology, Universitätsklinik Charité, Campus Virchow Klinikum, 13353 - Berlin/DE
  • 20Klinik Für Urologie, Helios Klinikum Erfurt, Erfurt/DE

Abstract

Background

Tyrosine kinase inhibitors (TKI) and nivolumab (NIVO) are key components of systemic therapies in metastatic renal cell carcinoma (mRCC). We tested if TKI induction followed by an early switch to NIVO improved outcome in mRCC.

Methods

Key inclusion criteria were measurable advanced or metastatic ccRCC, ECOG PS 0-2, adequate organ function, and PR or SD after sunitinib (50 mg, 4-2 regime) or pazopanib (800 mg OD) for 10-12 weeks. 1:1 randomized to either continue TKI treatment or receive nivolumab 240 or 480 mg IV q2-4wks, until PD or intolerance. Imaging occurred q12wks and health-related quality of life (HR-QoL) was assessed monthly x3 and q12wks thereafter (FKSI-15). Primary and key secondary endpoints were survival rate at 2 years and ORR, respectively. The trial stopped prematurely for low accrual after 49 of 244 patients were randomized.

Results

25 and 24 pts. were randomized to receive NIVO or TKI continuation, respectively. Median age was 65 years (range: 35-79), 40 pts. (82%) were male and 2 pts. (4%) had an ECOG PS of 2. MSKCC risk categories: favorable, intermediate, poor were (n; %): 15 (31), 32 (65) and 2 (4). Pazopanib was used in 22 (45). Response to TKI induction was PR in 29 (59) and SD in 20 (41). In the ITT population, best overall response rate measured from start of induction therapy was not significantly different for NIVO vs. TKI (64 vs. 70%, P = 0.76). However, when measured from time of randomization, ORR for NIVO vs. TKI was 16 vs. 48% (P = 0.029). Adverse events (AE) for NIVO vs. TKI occurred in 96% vs. 100% (all grades) and 44% vs. 67% (grades 3-5), respectively. Serious AE (SAE) for NIVO vs. TKI continuation were reported in 10 (40) and 9 (38), respectively.Table:

959P Best overall response to nivolumab or TKI treatment (ITT population)

From start of TKI inductionFrom randomization
CategoryNIVOTKITotalNIVOTKITotal
n252348252348
CR--1 (4%)1 (2%)--1 (4%)1 (2%)
PR16 (64%)15 (65%)31 (65%)4 (16%)10 (43%)14 (29)
SD9 (36%)7 (30%)16 (33%)6 (24%)7 (30%)13 (27%)
PD------11 (44%)3 (13%)14 (29%)
NE------4 (16%)2 (9%)6 (12%)

Conclusions

TKI induction followed by early switch to NIVO did not improve ORR in patients responsive to TKI. These results do not support the notion that TKI pretreatment sensitizes for nivolumab efficacy. Major limitations of our trial are the premature closure and the limited sample size.

Clinical trial identification

2016-002170-13; NCT02959554.

Editorial acknowledgement

Legal entity responsible for the study

AIO-Studien-gGmbH, Berlin.

Funding

Bristol-Myers Squibb.

Disclosure

V. Grünwald: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Shareholder / Stockholder / Stock options: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Ipsen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Eisai; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Novartis; Research grant / Funding (self): Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Shareholder / Stockholder / Stock options: AstraZeneca; Advisory / Consultancy: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Cerulean; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Shareholder / Stockholder / Stock options: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: Art tempi; Advisory / Consultancy, Speaker Bureau / Expert testimony: Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony: COCS; Advisory / Consultancy, Speaker Bureau / Expert testimony: ClinSol; Advisory / Consultancy, Speaker Bureau / Expert testimony: EUSAPharm; Advisory / Consultancy, Speaker Bureau / Expert testimony: MedUpdate; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Serono; Advisory / Consultancy, Speaker Bureau / Expert testimony: MedKomAkademie; Advisory / Consultancy, Speaker Bureau / Expert testimony: NewConceptOncology; Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Johnson & Johnson; Advisory / Consultancy, Speaker Bureau / Expert testimony: PharmaMar; Advisory / Consultancy, Speaker Bureau / Expert testimony: PeerVoice; Advisory / Consultancy, Speaker Bureau / Expert testimony: StreamedUp!; Advisory / Consultancy, Speaker Bureau / Expert testimony: ThinkWired!. All other authors have declared no conflicts of interest.