Nivolumab (RCC / Urothelial)

DURATION: treatment should be continued as long as clinical benefit is observed or until no longer tolerated; for adjuvant therapy the maximum treatment duration is 12 months. SCHEDULE SWITCHING: if RCC or MIUC (adjuvant) patients switch from 240 mg every 2 weeks to 480 mg every 4 weeks, the first 480 mg dose should be given two weeks after the last 240 mg dose; conversely for melanoma or RCC switching from 480 mg every 4 weeks to 240 mg every 2 weeks, the first 240 mg dose should be given four weeks after the last 480 mg dose. RCC IN COMBINATION WITH IPILIMUMAB: combination phase for 4 dosing cycles — nivolumab 3 mg/kg every 3 weeks over 30 minutes with ipilimumab 1 mg/kg every 3 weeks over 30 minutes; then monotherapy phase 240 mg every 2 weeks over 30 minutes (first dose 3 weeks after the last combination dose) or 480 mg every 4 weeks over 60 minutes (first dose 6 weeks after the last combination dose). RCC IN COMBINATION WITH CABOZANTINIB: nivolumab 240 mg every 2 weeks over 30 minutes or 480 mg every 4 weeks over 60 minutes with cabozantinib 40 mg once daily orally; nivolumab continued until disease progression, unacceptable toxicity, or up to 24 months, cabozantinib until progression or unacceptable toxicity. UROTHELIAL CARCINOMA IN COMBINATION WITH CISPLATIN AND GEMCITABINE: combination phase up to 6 cycles — nivolumab 360 mg every 3 weeks over 30 minutes with cisplatin and gemcitabine every 3 weeks; then monotherapy 240 mg every 2 weeks or 480 mg every 4 weeks over 30 minutes, until progression, unacceptable toxicity or up to 24 months. DOSE MODIFICATION: dose escalation or reduction is not recommended; dosing delay or discontinuation may be required based on individual safety and tolerability (see the SPC Table 15 for immune-related adverse reaction management). When nivolumab is given with ipilimumab, if either agent is withheld the other should also be withheld. LIVER ENZYMES WITH CABOZANTINIB IN RCC: if ALT or AST is greater than 3 x ULN but 10 x ULN or less without concurrent total bilirubin 2 x ULN or more, withhold both agents until recovery to Grade 0-1; if ALT or AST is greater than 10 x ULN, or greater than 3 x ULN with concurrent total bilirubin 2 x ULN or more, permanently discontinue both. ELDERLY: no dose adjustment required for patients 65 years and over. HEPATIC IMPAIRMENT: no dose adjustment in mild or moderate impairment; data in severe impairment are too limited to draw conclusions. SOURCE NOTE: eMC §4.2, §4.4 and §4.8 are truncated at the source-fetch limit and no eMC §4.5 interactions section was retrieved.

CALCULATOR DISABLED — the 3 mg/kg figure applies ONLY to adolescents 12 years and older weighing under 50 kg; at or above 50 kg the flat adult dose applies. Applies only to adolescents 12 years of age and older weighing less than 50 kg, for the monotherapy indications listed in SPC Table 1 (melanoma, renal cell carcinoma, adjuvant muscle-invasive urothelial carcinoma). Adolescents 12 years and older weighing at least 50 kg receive the adult flat doses (240 mg every 2 weeks or 480 mg every 4 weeks). In combination with ipilimumab for melanoma, adolescents 12 years and older receive nivolumab 1 mg/kg every 3 weeks over 30 minutes regardless of weight during the combination phase. No paediatric posology is given in the SPC for children under 12 years.