LAUSR

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. 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.