Impact of corticosteroids on nivolumab activity in metastatic clear cell renal cell carcinoma.

Date 30 September 2019
Event ESMO 2019 Congress
Session Poster Display session 3
Topics Renal Cell Cancer
Presenter Felix Lefort
Citation Annals of Oncology (2019) 30 (suppl_5): v356-v402. 10.1093/annonc/mdz249
Authors F. Lefort1, C. Dalban2, M. Gross-Goupil3, B. Laguerre4, P. Barthelemy5, V. Sarradin6, B. Chanez7, S. Negrier8, L. Geoffrois9, P. Gillon10, M. De Vries11, S. Ladoire12, C. Bolognini13, M. Laramas14, F. Priou15, S. Oudard16, S. Chabot17, F. Tantot18, B. Escudier19, L. Albiges20
  • 1Medical Oncology, CHU Bordeaux - Hopital St. André, 33000 - Bordeaux/FR
  • 2Clinical Research, Centre Léon Bérard, 69008 - Lyon/FR
  • 3Medical Oncology, CHU Bordeaux Hopital St. André, 33000 - Bordeaux/FR
  • 4Medical Oncology, Centre Eugene - Marquis, 35042 - Rennes/FR
  • 5Medical Oncology, C.H.U. Strasbourg-Nouvel Hopital Civil, 67000 - Strasbourg/FR
  • 6Medical Oncology, Institut Universitaire du Cancer -Toulouse- Oncopole, 31059 - Toulouse/FR
  • 7Medical Oncology, Institute Paoli Calmettes, 13274 - Marseille/FR
  • 8Medical Oncology, Centre Léon Bérard, 69008 - Lyon/FR
  • 9Medical Oncology, Institut de Cancérologie de Lorraine - Alexis Vautrin, 54519 - Vandoeuvre les Nancy/FR
  • 10Radiotherapy, Centre Antoine Lacassagne, 06189 - Nice/FR
  • 11Medical Oncology, Institut de cancérologie de l'Ouest - Paul Papin, 49055 - Angers/FR
  • 12Medical Oncology, Centre Georges-François Leclerc (Dijon), 21000 - Dijon/FR
  • 13Medical Oncology, CHRU Besancon - Hopital Jean Minjoz, 25030 - Besançon/FR
  • 14Medical Oncology, Grenoble Alpes University Hospital, 38700 - La Tronche/FR
  • 15Medical Oncology, CHD Vendee - Hopital Les Oudairies, 85925 - La Roche sur Yon/FR
  • 16Medical Oncology, Hopital European George Pompidou, 75015 - Paris/FR
  • 17Clinical Research, Centre Léon Bérard, 69008 - LYON/FR
  • 18Research And Development, Unicancer, 75654 - PARIS/FR
  • 19Medical Oncology, Gustave Roussy - Cancer Campus, 94805 - Villejuif/FR
  • 20Medical Oncology, Gustave Roussy, 94805 - Villejuif/FR

Abstract

Background

Nivolumab is a standard of care in patients (pts) with metastatic clear cell renal cell carcinoma (mccRCC) after failure of prior anti-angiogenic tyrosine-kinase inhibitors (TKIs). We evaluated the impact of corticosteroids (CS) during nivolumab in pts with mccRCC as part of a prospective clinical trial.

Methods

We conducted an ancillary study of the GETUG-AFU 26 NIVOREN study (NCT03013335), a multicenter prospective phase II safety study of nivolumab in mccRCC after progression on anti-angiogenic TKIs. Patients receiving CS at nivolumab initiation were excluded. Overall survival (OS) and progression free survival (PFS) of pts exposed to CS (≥ 10 mg of prednisone equivalents) or not during nivolumab were assessed. To overcome immortal time bias, we used two different landmark analysis methods. We first excluded pts who progressed or died before specified landmark timepoints (12 and 16 weeks). In a second method, patients treated with CS before landmark timepoints (12 and 16 and 24 weeks) were used to evaluate the effect of an early exposition to CS.

Results

Among the 665 evaluable pts, with a median follow up of 23.9 months, 113 (17 %) were exposed to CS during nivolumab, mainly to treat immune-related adverse events of any grade (74%). Other indications included infections (15%), complications of radiotherapy and chronic obstructive pulmonary disease. Median time to the first CS treatment was 21.6 weeks. Using a landmark at 12 weeks, OS rate at 12 months were 85.6% and 73.5% in pts exposed or not to CS [hazard ratio (HR), 0.57; p = 0.0017]. PFS rate at 12 months were 61.1% and 41.6% in pts exposed or not to CS (HR, 0.63; p = 0.0065). Landmark analyses at 16 weeks showed similar results. With the second landmark method, no differences in PFS or OS were observed between groups at 12 and 16 weeks. With a landmark set at 24 weeks, OS was similar in pts exposed or not to CS (HR, 1.14; p = 0.55).

Conclusions

The use of CS during nivolumab in mccRCC is not associated with a detrimental effect on survival outcomes. The positive association of corticosteroid use for irAEs with outcomes was not confirmed by second landmark modalities. Immortal time bias should be carefully considered when studying time-dependent variable.

Clinical trial identification

NCT03013335.

Editorial acknowledgement

Legal entity responsible for the study

UNICANCER.

Funding

Bristol-Myers Squibb.

Disclosure

M. Gross-Goupil: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis. B. Laguerre: Honoraria (self), Travel / Accommodation / Expenses: BMS; Honoraria (self), Travel / Accommodation / Expenses: Pfizer; Honoraria (self): Novartis; Honoraria (self): Ipsen. P. Barthelemy: Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Janssen-Cilag; Honoraria (self), Advisory / Consultancy: Sanofi. S. Negrier: Honoraria (self): Pfizer; Honoraria (self): Bms; Honoraria (self): Novartis; Honoraria (self): IPSEN; Honoraria (self): Euspharma. L. Geoffrois: Honoraria (self), Travel / Accommodation / Expenses: MSD; Honoraria (self), Travel / Accommodation / Expenses: BMS; Honoraria (self): Ipsen; Honoraria (self): Novartis; Travel / Accommodation / Expenses: Merck. S. Ladoire: Advisory / Consultancy, Travel / Accommodation / Expenses: BMS. M. Laramas: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: SANOFI; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: Amgen; Speaker Bureau / Expert testimony: IPSEN; Speaker Bureau / Expert testimony: Janssen; Travel / Accommodation / Expenses: Eisai. S. Oudard: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Ipsen. B. Escudier: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Roche; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Eusa; Advisory / Consultancy, Research grant / Funding (institution): Avevo; Advisory / Consultancy, Research grant / Funding (institution): Pfizer. L. Albiges: Advisory / Consultancy, Compensated to institution: Pfizer; Advisory / Consultancy, Compensated to institution: Novartis; Advisory / Consultancy, Compensated to institution: BMS; Advisory / Consultancy, Compensated to institution: Ipsen; Advisory / Consultancy, Compensated to institution: Roche; Advisory / Consultancy, Compensated to institution: MSD; Advisory / Consultancy, Compensated to institution: AstraZeneca. All other authors have declared no conflicts of interest.