Table 2.

Alternative dosing regimens of anticancer drugs and recommendations for their implementation

Drug	Approved dosing regimen	Alternative dosing regimen	Available evidence	Translated into drug label	Author’s recommendation	Reference
Alternative dosing leading to equivalent exposure
Abiraterone	1000 mg fasted	250 mg fed	Exposure below bioequivalence margins + equivalent PSA change	No	Establish no-effect boundaries in exposure–response analysis + equivalent exposure	14
Atezolizumab	1200 mg Q3W	1680 mg Q4W 840 mg Q2W	Equivalent exposure and safety based on modeling	Yes	Implement in label agreement	15
Ceritinib	750 mg fasted	450 mg fed	Equivalent exposure and improved safety16 Consistent efficacy17	Yes	Implement in label agreement	16,17
Cetuximab	250 mg/m2 Q1W	500 mg/m2 Q2W	Non-inferior efficacy	No	Implement in clinical practice	9
Erlotinib	150 mg QD	75 mg + ritonavir 200 mg QD	Comparable exposure in a single-dose PK study	No	Equivalent exposure needs to be demonstrated before implementation	18
Ibrutinib	140 mg QD	15 mg + itraconazole 200 mg QD	Comparable exposure in a single-dose PK study	No	Equivalent exposure needs to be demonstrated before implementation	19
Nivolumab	3 mg/kg Q2W	240 mg Q2W	Equivalent exposure based on modeling	Yes	Implement in label agreement	20
Nivolumab	240 mg Q2W	480 mg Q4W	Equivalent exposure based on modeling	Yes	Implement in label agreement	21
Pazopanib	800 mg fasted	600 mg fed	Equivalent exposure	No	Implement in clinical practice	5
Pembrolizumab	2 mg/kg Q3W	200 mg Q3W	Equivalent exposure based on modeling	Yes	Implement in label agreement	22
Pembrolizumab	200 mg Q3W	400 mg Q6W	Equivalent exposure based on modeling	Yes	Implement in label agreement	23
Sunitinib	50 mg 4 weeks on, 2 weeks off	50 mg 2 weeks on, 1 week off	Equivalent efficacy and improved safety	No	Implement in clinical practice	24
Alternative dosing regimens leading to lower or shorter exposure
Cabazitaxel	25 mg/m2	20 mg/m2	Non-inferior efficacy + improved safety	Yes	Implement in label agreement	25
Dasatinib	70 mg BID	100 mg QD	Non-inferior efficacy	Yes	Implement in label agreement	26
Dasatinib	100 mg QD	50 mg QD	Similar efficacy + improved safety	No	Non-inferiority on clinical endpoints needs to be demonstrated before implementation	27
Imatinib	Until progression	Until undetectable BCR-ABL transcript levels	Meta-analysis of 12 cohort studies	No	Implement in clinical practice	7
Trastuzumab	12 months	6 months	Non-inferior efficacy	No	Implement in clinical practice	8
Alternative dosing regimens leading to higher exposure
Imatinib	400 mg QD	400 mg BID for patients with GIST with KIT exon 9 mutation	Superior efficacy	No	Implement in clinical practice	28
Sunitinib	50 mg 4 weeks on, 2 weeks off	700 mg Q2W	Clinical trial ongoing	No	Superiority to standard-of-care needs to be demonstrated before implementation	NCT03909724

BID, twice daily; GIST, gastrointestinal stromal tumor; PK, pharmacokinetic; PSA, prostate specific antigen; QD, once daily; Q1W, every week; Q2W, every 2 weeks; Q3W, every 3 weeks; Q4W, every 4 weeks; Q6W, every 6 weeks.