Model-based simulation to support the extended dosing regimens of atezolizumab

Chou, Chen Hsi; Hsu, Li-Feng

doi:10.1007/s00228-020-02980-3

Cited by 8 publications

(15 citation statements)

References 16 publications

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“…In the treatment of NSCLC, small cell lung cancer, and hepatocellular carcinoma, only the fixed dose of 1200 mg Q3W was evaluated [ 95 – 103 ]. Doses of 840 mg Q2W, or 1680 mg Q4W for NSCLC were proposed based on modeling studies [ 104 , 105 ]. In the treatment of triple negative breast cancer, the choice of 840 mg Q2W was not argued for but fits more easily into the nab-paclitaxel regimen [ 106 ].…”

Section: Therapeutic Antibodies Targeting Pd-l1mentioning

confidence: 99%

“…Atezolizumab was initially developed at a dose of 15 mg/kg. Two in silico modeling analyses showed comparable efficacy and safety for doses of 15 mg/kg Q3W, 840 mg Q2W, 1200 mg Q3W and 1680 mg/kg Q4W, corresponding to a serum concentration of 6 mg/mL [ 104 , 105 ]. In clinical studies, the average patient weight was 70 to 80 kg, the switch to the fixed dose of 840 mg corresponds to the dose for a 56 kg person.…”

Section: Therapeutic Antibodies Targeting Pd-l1mentioning

confidence: 99%

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Immune checkpoint-targeted antibodies: a room for dose and schedule optimization?

et al. 2022

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Anti-CTLA-4 and anti-PD-1/PD-L1 immune checkpoint inhibitors are therapeutic monoclonal antibodies that do not target cancer cells but are designed to reactivate or promote antitumor immunity. Dosing and scheduling of these biologics were established according to conventional drug development models, even though the determination of a maximum tolerated dose in the clinic could only be defined for anti-CTLA-4. Given the pharmacology of these monoclonal antibodies, their high interpatient pharmacokinetic variability, the actual clinical benefit as monotherapy that is observed only in a specific subset of patients, and the substantial cost of these treatments, a number of questions arise regarding the selected dose and the dosing interval. This review aims to outline the development of these immunotherapies and considers optimization options that could be used in clinical practice.

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Section: Therapeutic Antibodies Targeting Pd-l1mentioning

confidence: 99%

Section: Therapeutic Antibodies Targeting Pd-l1mentioning

confidence: 99%

Immune checkpoint-targeted antibodies: a room for dose and schedule optimization?

et al. 2022

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“…The Canadian Agency of Drugs and Technologies in Health simulated dosing regimens of pembrolizumab 4 mg/kg Q6W in patients weighing 70, 100, and 150 kg, all with trough target engagement above 97% ( 73 ). Comparison of the standard regimen of atezolizumab with several extended interval regimens showed that the predicted efficacy and safety of 1680 mg Q8W/1200 mg Q6W was not inferior to the standard 1200 mg Q3W ( 74 ).…”

Section: Dosing Regimen Optimizationmentioning

confidence: 99%

Dosing Regimens of Immune Checkpoint Inhibitors: Attempts at Lower Dose, Less Frequency, Shorter Course

Jiang

Liu

et al. 2022

Front. Oncol.

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Immune checkpoint inhibitors (ICIs) are a revolutionary breakthrough in the field of cancer by modulating patient’s own immune system to exert anti-tumor effects. The clinical application of ICIs is still in its infancy, and their dosing regimens need to be continuously adjusted. Pharmacokinetic/pharmacodynamic studies showed a significant plateau in the exposure-response curve, with high receptor occupancy and plasma concentrations achieved at low dose levels. Coupled with concerns about drug toxicity and heavy economic costs, there has been an ongoing quest to reevaluate the current ICI dosing regimens while preserving maximum clinical efficacy. Many clinical data showed remarkable anticancer effects with ICIs at the doses far below the approved regimens, indicating the possibility of dose reduction. Our review attempts to summarize the clinical evidence for ICIs regimens with lower-dose, less-frequency, shorter-course, and provide clues for further ICIs regimen optimization.

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“…УУР А (УДД 2). Комментарий: атезолизумаб** назначается в одной из следующих доз [90,[215][216][217] • Пациентам с распространенным плоскоклеточным РЛ с любым (или неизвестным) статусом PD-L1 может быть рекомендована комбинация ИТ с ХТ в следующем режиме: пембролизумаб** 200 мг 1 раз в 3 нед/400 мг 1 раз в 6 нед + # паклитаксел** 200 мг/м 2 в 1-й день + карбоплатин** AUC-6 (расчет точной дозы см. выше) в 1-й день каждые 3 нед, 4 курса; в дальнейшем -поддерживающая терапия пембролизумабом** до прогрессирования или развития непереносимой токсичности [79,271].…”

Section: уур C (удд 4)unclassified

“…• 1200 мг в/в каждые 3 нед; • 840 мг в/в каждые 2 нед; • 1680 мг в/в каждые 4 нед [85,90,217]. УУР С (УДД 4) [90].…”

Section: лекарственная терапия 2-й линииunclassified

Malignant neoplasm of the bronchi and lung: Russian clinical guidelines

Лактионов

Kaytukovа²,

Borisova³

et al. 2022

J. Mod. Onco.

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Model-based simulation to support the extended dosing regimens of atezolizumab

Cited by 8 publications

References 16 publications

Immune checkpoint-targeted antibodies: a room for dose and schedule optimization?

Immune checkpoint-targeted antibodies: a room for dose and schedule optimization?

Dosing Regimens of Immune Checkpoint Inhibitors: Attempts at Lower Dose, Less Frequency, Shorter Course

Malignant neoplasm of the bronchi and lung: Russian clinical guidelines

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