A six-weekly dosing schedule for pembrolizumab in patients with cancer based on evaluation using modelling and simulation

Lala, Mallika; Li, Tommy Ruosi; Alwis, Dinesh P. de; Sinha, Vikram; Mayawala, Kapil; Yamamoto, Noboru; Siu, Lillian L.; Chartash, Elliot; Aboshady, Hesham; Jain, Lokesh

doi:10.1016/j.ejca.2020.02.016

Cited by 116 publications

(101 citation statements)

References 13 publications

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“…These are similar to the historically reported response rates with pembrolizumab in metastatic melanoma. Additionally, exposure concentrations observed in patients in this study with the 400 mg Q6W regimen were within the 90% prediction intervals of simulated concentrations from the model-based study (65). C min with 400 mg Q6W was 18% lower than 200 mg Q3W, while C max was 38% lower than the maximum clinically tested dose of 10 mg/kg Q2W.…”

Section: Clinical Evidence Behind Extended-interval Dosing Strategiessupporting

confidence: 65%

“…Subsequently, another modeling study simulated pembrolizumab concentration time profiles by utilizing the PPK model based on data from 2,993 participants in five clinical trials of patients with multiple tumor types (65). This study also measured steady-state PK profiles to compare efficacy and safety of pembrolizumab 400 mg Q6W with the standard doses of 200 mg Q3W and 2 mg/kg Q3W.…”

Section: Exposure-matching: Development Of Extended-interval Dosing Smentioning

confidence: 99%

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Extended-Interval Dosing Strategy of Immune Checkpoint Inhibitors in Lung Cancer: Will it Outlast the COVID-19 Pandemic?

2020

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Patients with lung cancer are particularly vulnerable to complications from coronavirus disease-2019 (COVID-19). Recurrent hospital visits and hospital admission are potential risk factors for acquiring infection with its causative pathogen, severe acute respiratory syndrome coronavirus−2 (SARS-CoV-2). As immune checkpoint inhibitors (ICIs) constitute the therapeutic backbone for the vast majority of patients with advanced lung cancer in the absence of actionable driver oncogenes, there have been intense discussions within the oncology community regarding risk-benefit of delaying these treatments or use of alternative extended-interval treatment strategies to minimize the risk of viral transmission secondary to unintended nosocomial exposures. In the midst of the COVID-19 pandemic, the U.S. Food and Drug Administration (FDA) granted accelerated approval for extended-interval strategy of pembrolizumab at a dose of 400 mg every 6 weeks for all already approved oncologic indications. Herein, we summarize the evidence from the in silico pharmacokinetic modeling/simulation studies supporting extended-interval dosing strategies for the ICIs used in lung cancer. We further review the evolving clinical evidence behind these approaches and predict that they will continue to be used in routine practice even long after the pandemic, particularly for patients with durable disease control.

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Section: Clinical Evidence Behind Extended-interval Dosing Strategiessupporting

confidence: 65%

Section: Exposure-matching: Development Of Extended-interval Dosing Smentioning

confidence: 99%

Extended-Interval Dosing Strategy of Immune Checkpoint Inhibitors in Lung Cancer: Will it Outlast the COVID-19 Pandemic?

2020

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“…In contrast, patients who need to return for immunotherapy or chemotherapy could be referred to the local hospitals that had a lesser clinical burden of COVID-19. The safety and efficacy are similar for patients transitioning from nivolumab 3 mg/kg every 2 weeks to 480 mg every 4 weeks 19 or from pembrolizumab 2 mg/ kg every 3 weeks to 400 mg every 6 weeks, 20 and long dosing intervals decrease the frequency of visits to the hospital and have the potential to reduce the risk of exposure to COVID-19. Both immunotherapy and chemotherapy could notably influence the host immune system, which may interact with SARS-CoV-2 and cause extra damage.…”

Section: Discussionmentioning

confidence: 95%

Real-World Scenario of Patients With Lung Cancer Amid the Coronavirus Disease 2019 Pandemic in the People’s Republic of China

Fu¹,

Wu²,

Zhang³

et al. 2020

JTO Clinical and Research Reports

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Introduction: The coronavirus disease 2019 (COVID-19) outbreak throughout the world has affected millions of people in many ways, putting a huge burden on the health care system. The ongoing outbreak of this respiratory disease has posed critical challenges to public health, research, and medical communities around the world. This study aimed at evaluating the impact of COVID-19 pandemic on patients with lung cancer in the People's Republic of China.

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“…For immune checkpoint inhibitors, a less frequent schedule of infusion may be considered if the risks of travel are considered excessively high. For nivolumab and pembrolizumab, alternative less frequent dosing regimen have been reported in other cancer types, which may be extrapolated to be used in HCC patients during the pandemic [47,48].…”

Section: Advanced-stage Hccmentioning

confidence: 99%

Impacts of COVID-19 on Liver Cancers: During and after the Pandemic

Chan

Kudo

2020

Liver Cancer

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Background: The pandemic of coronavirus disease 2019 (COVID-19) has diverted resources from healthcare services for patients with chronic medical illness such as cancer. COVID-19 also causes organ dysfunction, complicating cancer treatment. In most countries with an outbreak of COVID-19, modifications of cancer management have been adopted to accommodate the crisis and minimize the exposure of cancer patients to the infection. In countries where COVID-19 numbers are subsiding, medical teams should also be prepared to resume normal practices gradually. Here, we aim to review the literature on the impact of COVID-19 on patients with hepatocellular carcinoma (HCC) as well as discuss modifications to the management of HCC during and after recovery from the pandemic. Summary: Based on current data, 10-40% of patients with COVID-19 have hepatic injury characterized by an elevation of transaminases and/or hyperbilirubinemia. Multiple mechanisms contribute to the hepatic injury, including direct viral entry to hepatocytes/cholangiocytes, immune-mediated hepatitis, hypoxia, and drug-related hepatotoxicity. In patients with HCC, COVID-19 may exacerbate existing chronic liver disease and complicate the management of cancer. Cancer patients generally have a higher risk of infection and worse outcome, especially those who have recently undergone cancer treatment. Although HCC is under-represented in COVID-19 series, mitigation measures should be implemented to minimize the exposure of patients to the virus. A decision on the treatment of HCC should be balanced with consideration of the availability of medical resources, the level of infection risk of COVID-19, and the risk-benefit ratio of the individual patient. In areas where the COVID-19 outbreak is subsiding, clinicians should be pre

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A six-weekly dosing schedule for pembrolizumab in patients with cancer based on evaluation using modelling and simulation

Cited by 116 publications

References 13 publications

Extended-Interval Dosing Strategy of Immune Checkpoint Inhibitors in Lung Cancer: Will it Outlast the COVID-19 Pandemic?

Extended-Interval Dosing Strategy of Immune Checkpoint Inhibitors in Lung Cancer: Will it Outlast the COVID-19 Pandemic?

Real-World Scenario of Patients With Lung Cancer Amid the Coronavirus Disease 2019 Pandemic in the People’s Republic of China

Impacts of COVID-19 on Liver Cancers: During and after the Pandemic

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