Safety and Efficacy of Extended Interval Dosing for Immune Checkpoint Inhibitors in Non–Small Cell Lung Cancer During the COVID-19 Pandemic

Hijmering-Kappelle, Lucie; Hiltermann, T. Jeroen N.; Bensch, Frederike

doi:10.1016/j.cllc.2021.12.005

Cited by 14 publications

(21 citation statements)

References 5 publications

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“…There have been retrospective studies assessing the real-world effects of extended dosing intervals of pembrolizumab in patients with NSCLC and PD-L1 ≥5 0%. The focus of these studies was to examine the safety and toxicity of a higher dose of pembrolizumab over a longer interval, and they have generally noted similar adverse event profiles [ 15 , 16 , 17 , 18 ]. Patient outcomes with respect to OS were evaluated in the Netherlands cohort; in the 54 patients who received single-agent immunotherapy, there was no statistically significant difference between single-agent pembrolizumab 200 mg given Q3W vs.400 mg Q6W, congruent with our results.…”

Section: Discussionmentioning

confidence: 99%

Alternate Pembrolizumab Dosing Interval in Advanced NSCLC with PD-L1 TPS ≥ 50%: 3 Weekly Compared to 6 Weekly Dosing

Jones¹,

Rittberg²,

Leung³

et al. 2022

Current Oncology

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Background: A fixed dose of 200 mg of pembrolizumab every 3 weeks (Q3W) is the standard of care for patients with stage IV non-small cell lung cancer (NSCLC) and PDL1 ≥50%. In April 2020, based on pharmacokinetic modeling without formal comparative studies, the FDA approved 400 mg every 6 weeks (Q6W). Pharmacokinetic studies also suggested comparable target engagement with weight-based and flat dosing for the respective schedules. The objective of this study was to determine if overall survival (OS) differs based on the Q3W vs. Q6W dosing schedule of pembrolizumab. Methods: BC Cancer patients with stage IV NSCLC and PDL1 ≥50% treated with pembrolizumab were retrospectively reviewed. Patients were treated with weight-based dosing, per institution standard, of pembrolizumab 2 mg/kg Q3W or 4 mg/kg Q6W. Patient demographics, treatment and outcome were recorded. Patients were assigned to Q3W or Q6W according to the schedule that was used for the majority of treatment (greater than 50%). Results: 718 patients with NSCLC and PDL1 ≥50% received first-line pembrolizumab between 2017 and2021, Q3W/Q6W dosing 677/41 patients. Baseline characteristics with respect to age, sex, smoking status, histology and performance status (PS) were similar between groups. In the multivariate model, including age, sex, PS and dosing schedule, the hazard ratio for death (HR) for OS Q3W vs. Q6W was 0.759 (p = 0.230). A 2:1 case-matched analysis for OS was performed, controlling for sex, age ± 5 years, PS and duration on pembrolizumab ± 2 months for Q3W vs. Q6W (n = 113) with a HR 0.834 (p = 0.500). Conclusions: There was no OS difference demonstrated with pembrolizumab dosing Q3W compared to Q6W in a multivariate analysis that included age, sex and PS. A case-matched analysis that controlled for these variables and for duration of treatment confirmed these findings. This study supports the use of Q6W pembrolizumab dosing, allowing for less frequent interactions with the medical system.

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Section: Discussionmentioning

confidence: 99%

Alternate Pembrolizumab Dosing Interval in Advanced NSCLC with PD-L1 TPS ≥ 50%: 3 Weekly Compared to 6 Weekly Dosing

Jones¹,

Rittberg²,

Leung³

et al. 2022

Current Oncology

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“…Interim analysis of the phase III/IV CheckMate 384 trial similarly suggests that 4 weekly 480 mg nivolumab maintains efficacy and safety compared to 2 weekly 240 mg dosing. 47 Additionally, a retrospective single-centre Dutch study evaluated the safety and efficacy of decreased anti-PD1 frequency, 56 comparing 3 weekly 200 mg versus 6 weekly 400 mg pembrolizumab and 2 weekly 240 mg versus 4 weekly 480 mg nivolumab. The efficacy of the extended frequency regimens was comparable.…”

Section: Optimal Frequency Of Therapymentioning

confidence: 99%

What is the optimal duration, dose and frequency for anti-PD1 therapy of non-small cell lung cancer?

Kuah,

Monfries,

Quartagno

et al. 2023

Ther Adv Med Oncol

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Over the past decade, immune checkpoint inhibitors (ICIs) have transformed the management of multiple malignancies including lung cancer. However, the optimal use of these agents in terms of duration, dose and administration frequency remains unknown. Focusing on anti-PD1 agents nivolumab and pembrolizumab in the context of non-small cell lung cancer, we argue that several lines of evidence suggest current administration regimens of these drugs may result in overtreatment with potentially important implications for cost, quality of life and toxicity. This review summarizes evidence for the scope to optimize anti-PD1 regimens, the limitations of existing data and potential approaches to solve these problems including with a novel multi-arm clinical trial design implemented in the recently opened REFINE-Lung study.

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“…The duration of the COVID-19 pandemic remains unpredictable and should not prevent the use of ICIs in patients with highly responsive tumors (157)(158)(159). The current consensus is that both physicians and patients preferred high-dose, extended-interval regimen to reduce the risk of exposure (73,(160)(161)(162)(163). There was no difference in safety and efficacy between extended-interval dosing and standard dosing pembrolizumab or durvalumab in NSCLC patients during the COVID-19 pandemic, while PFS, OS were longer in patients treated with extended-interval nivolumab (163).…”

Section: Medication Strategies For Icis Under the Covid-19 Pandemicmentioning

confidence: 99%

“…The current consensus is that both physicians and patients preferred high-dose, extended-interval regimen to reduce the risk of exposure (73,(160)(161)(162)(163). There was no difference in safety and efficacy between extended-interval dosing and standard dosing pembrolizumab or durvalumab in NSCLC patients during the COVID-19 pandemic, while PFS, OS were longer in patients treated with extended-interval nivolumab (163). The safety and/or efficacy of the COVID-19 vaccine, as well as the interaction between the vaccine and the ICI, are inconclusive for patients treated with ICI whose immune systems are activated.…”

Section: Medication Strategies For Icis Under the Covid-19 Pandemicmentioning

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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Safety and Efficacy of Extended Interval Dosing for Immune Checkpoint Inhibitors in Non–Small Cell Lung Cancer During the COVID-19 Pandemic

Cited by 14 publications

References 5 publications

Alternate Pembrolizumab Dosing Interval in Advanced NSCLC with PD-L1 TPS ≥ 50%: 3 Weekly Compared to 6 Weekly Dosing

Alternate Pembrolizumab Dosing Interval in Advanced NSCLC with PD-L1 TPS ≥ 50%: 3 Weekly Compared to 6 Weekly Dosing

What is the optimal duration, dose and frequency for anti-PD1 therapy of non-small cell lung cancer?

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

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