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

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...

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Main Authors: Lauren Jones, Rebekah Rittberg, Bonnie Leung, Aria Shokoohi, Alexandra Pender, Selina Wong, Zamzam Al-Hashami, Ying Wang, Cheryl Ho
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Current Oncology
Subjects:
Online Access:https://www.mdpi.com/1718-7729/29/11/685
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author Lauren Jones
Rebekah Rittberg
Bonnie Leung
Aria Shokoohi
Alexandra Pender
Selina Wong
Zamzam Al-Hashami
Ying Wang
Cheryl Ho
author_facet Lauren Jones
Rebekah Rittberg
Bonnie Leung
Aria Shokoohi
Alexandra Pender
Selina Wong
Zamzam Al-Hashami
Ying Wang
Cheryl Ho
author_sort Lauren Jones
collection DOAJ
description 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 (<i>p</i> = 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 (<i>n</i> = 113) with a HR 0.834 (<i>p</i> = 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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spelling doaj.art-e00a766de58841df86bd311c86c0dc6b2023-11-24T08:03:12ZengMDPI AGCurrent Oncology1198-00521718-77292022-11-0129118686869210.3390/curroncol29110685Alternate Pembrolizumab Dosing Interval in Advanced NSCLC with PD-L1 TPS ≥ 50%: 3 Weekly Compared to 6 Weekly DosingLauren Jones0Rebekah Rittberg1Bonnie Leung2Aria Shokoohi3Alexandra Pender4Selina Wong5Zamzam Al-Hashami6Ying Wang7Cheryl Ho8Department of Medical Oncology, BC Cancer, Vancouver, BC V5Z 4E6, CanadaDepartment of Medical Oncology, BC Cancer, Vancouver, BC V5Z 4E6, CanadaDepartment of Medical Oncology, BC Cancer, Vancouver, BC V5Z 4E6, CanadaFaculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R7, CanadaDepartment of Medical Oncology, The Royal Free NHS Foundation Trust, London NW3 2QG, UKDepartment of Medical Oncology, BC Cancer, Victoria, BC V8R 6V5, CanadaDepartment of Medical Oncology, Sultan Qaboos Comprehensive Cancer Care and Research Center, Muscat 111, OmanDepartment of Medical Oncology, BC Cancer, Vancouver, BC V5Z 4E6, CanadaDepartment of Medical Oncology, BC Cancer, Vancouver, BC V5Z 4E6, CanadaBackground: 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 (<i>p</i> = 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 (<i>n</i> = 113) with a HR 0.834 (<i>p</i> = 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.https://www.mdpi.com/1718-7729/29/11/685PDL1pembrolizumabdosing scheduleNSCLC
spellingShingle Lauren Jones
Rebekah Rittberg
Bonnie Leung
Aria Shokoohi
Alexandra Pender
Selina Wong
Zamzam Al-Hashami
Ying Wang
Cheryl Ho
Alternate Pembrolizumab Dosing Interval in Advanced NSCLC with PD-L1 TPS ≥ 50%: 3 Weekly Compared to 6 Weekly Dosing
Current Oncology
PDL1
pembrolizumab
dosing schedule
NSCLC
title Alternate Pembrolizumab Dosing Interval in Advanced NSCLC with PD-L1 TPS ≥ 50%: 3 Weekly Compared to 6 Weekly Dosing
title_full Alternate Pembrolizumab Dosing Interval in Advanced NSCLC with PD-L1 TPS ≥ 50%: 3 Weekly Compared to 6 Weekly Dosing
title_fullStr Alternate Pembrolizumab Dosing Interval in Advanced NSCLC with PD-L1 TPS ≥ 50%: 3 Weekly Compared to 6 Weekly Dosing
title_full_unstemmed Alternate Pembrolizumab Dosing Interval in Advanced NSCLC with PD-L1 TPS ≥ 50%: 3 Weekly Compared to 6 Weekly Dosing
title_short Alternate Pembrolizumab Dosing Interval in Advanced NSCLC with PD-L1 TPS ≥ 50%: 3 Weekly Compared to 6 Weekly Dosing
title_sort alternate pembrolizumab dosing interval in advanced nsclc with pd l1 tps ≥ 50 3 weekly compared to 6 weekly dosing
topic PDL1
pembrolizumab
dosing schedule
NSCLC
url https://www.mdpi.com/1718-7729/29/11/685
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