Dosing of PD-1 and PD-L1 inhibitors: Cost saving initiatives for significantly decreasing associated expenditure

Gilbar, Peter J; Davis, Mark

doi:10.1177/1078155220974077

Cited by 7 publications

(7 citation statements)

References 25 publications

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“…24 This not only increases that likelihood that ICI therapy will be used closer to death but also the massive financial cost associated with these drugs in a setting that may not be appropriate. 25 Contact with palliative care services declined from our original audit (57.4% to 44.5%). During the reaudit period significant interruptions in palliative care services occurred at the RCC making interpretation of these results unreliable.…”

Section: Discussionmentioning

confidence: 92%

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Retrospective analysis of mortality within 30 days of systemic anticancer therapy and comparison with a previous audit at an Australian Regional Cancer Centre

Zimbwa

Gilbar

Davis

et al. 2021

J Oncol Pharm Pract

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Purpose To retrospectively determine the rate of death occurring within 14 and 30 days of systemic anticancer therapy (SACT), compare this against a previous audit and benchmark results against other cancer centres. Secondly, to determine if the introduction of immune checkpoint inhibitors (ICI), not available at the time of the initial audit, impacted mortality rates. Method All adult solid tumour and haematology patients receiving SACT at an Australian Regional Cancer Centre (RCC) between January 2016 and July 2020 were included. Results Over a 55-month period, 1709 patients received SACT. Patients dying within 14 and 30 days of SACT were 3.3% and 7.0% respectively and is slightly higher than our previous study which was 1.89% and 5.6%. Mean time to death was 15.5 days. Males accounted for 63.9% of patients and the mean age was 66.8 years. 46.2% of the 119 patients dying in the 30 days post SACT started a new line of treatment during that time. Of 98 patients receiving ICI, 22.5% died within 30 days of commencement. Disease progression was the most common cause of death (79%). The most common place of death was the RCC (38.7%). Conclusion The rate of death observed in our re-audit compares favourably with our previous audit and is still at the lower end of that seen in published studies in Australia and internationally. Cases of patients dying within 30 days of SACT should be regularly reviewed to maintain awareness of this benchmark of quality assurance and provide a feedback process for clinicians.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Retrospective analysis of mortality within 30 days of systemic anticancer therapy and comparison with a previous audit at an Australian Regional Cancer Centre

Zimbwa

Gilbar

Davis

et al. 2021

J Oncol Pharm Pract

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“…The duration of the therapies for 16 patients with TNBC varied from a few months up to 96 weeks. Following the suggested schedule, we thus simulate the dose regimen of 10 mg/kg administered q2w for a duration of 400 days, which is similar to other PD‐L1 immune‐checkpoint inhibitor therapies 17 . We proceed by simulating three cases for the same 10,000 VPs: untreated progression, unmasked antibody monotherapy, and PbTx monotherapy.…”

Section: Resultsmentioning

confidence: 99%

“…Following the suggested schedule, we thus simulate the dose regimen of 10 mg/kg administered q2w for a duration of 400 days, which is similar to other PD‐L1 immune‐checkpoint inhibitor therapies. 17 We proceed by simulating three cases for the same 10,000 VPs: untreated progression, unmasked antibody monotherapy, and PbTx monotherapy. The “untreated” case refers to allowing the dynamics of clinical progression to evolve without the addition of any external therapy.…”

Section: Resultsmentioning

confidence: 99%

Eliciting the antitumor immune response with a conditionally activated PD‐L1 targeting antibody analyzed with a quantitative systems pharmacology model

Ippolito,

Wang,

Zhang

et al. 2023

CPT Pharmacom & Syst Pharma

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Conditionally activated molecules, such as Probody therapeutics (PbTx), have recently been investigated to improve antitumoral response while reducing systemic toxicity. PbTx are engineered to be proteolytically activated by proteases that are preferentially active locally in the tumor microenvironment (TME). Here, we perform an exploratory study using our recently published quantitative systems pharmacology model, previously validated for other drugs, to evaluate the effectiveness and targeting specificity of an anti‐PD‐L1 PbTx compared to the non‐modified antibody. We have informed the model using the PbTx dynamics and pharmacokinetics published in the literature for anti‐PD‐L1 in patients with triple‐negative breast cancer (TNBC). Our results suggest masking of the antibody slightly decreases its efficacy, while increasing the localization of active therapeutic component in the TME. We also perform a parameter optimization for the PbTx design and drug dosing regimens to maximize the response rate. Although our results are specific to the case of TNBC, our findings are generalizable to any conditionally activated PbTx molecule in solid tumors and suggest that design of a highly effective and selective PbTx is feasible.

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“…The flat dose is equivalent to a BW-based dose for a patient weighing 100 kg, considerably above the weight of most patients. 12 Whether that has increased the likelihood of developing TTP is unknown but is an area of research that could be investigated further in regard to adverse effects attributed to ICIs.…”

mentioning

confidence: 99%

Case reports of acquired thrombotic thrombocytopenic purpura attributed to pembrolizumab

Gilbar

Dickey

2022

J Oncol Pharm Pract

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Dosing of PD-1 and PD-L1 inhibitors: Cost saving initiatives for significantly decreasing associated expenditure

Cited by 7 publications

References 25 publications

Retrospective analysis of mortality within 30 days of systemic anticancer therapy and comparison with a previous audit at an Australian Regional Cancer Centre

Retrospective analysis of mortality within 30 days of systemic anticancer therapy and comparison with a previous audit at an Australian Regional Cancer Centre

Eliciting the antitumor immune response with a conditionally activated PD‐L1 targeting antibody analyzed with a quantitative systems pharmacology model

Case reports of acquired thrombotic thrombocytopenic purpura attributed to pembrolizumab

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