Can Ipilimumab restore immune response in advanced NSCLC after progression on anti‐PD‐1/PD‐L1 agents?

Anti‐PD‐1/PD‐L1 agents play a crucial part in the treatment of non‐small cell cancer (NSCLC) demonstrating improved overall response rate (ORR) and overall survival (OS). Recent studies evaluating combination treatment with anti‐PD‐1 and anti‐CTLA‐4 suggests improved outcome but also increased toxic...

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Main Authors: Michal Sternschuss, Nir Peled, Aaron M. Allen, Elizabeth Dudnik, Ofer Rotem, Noga Kurman, Omer Gal, Hiba Reches, Alona Zer
Format: Article
Language:English
Published: Wiley 2020-08-01
Series:Thoracic Cancer
Subjects:
Online Access:https://doi.org/10.1111/1759-7714.13502
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author Michal Sternschuss
Nir Peled
Aaron M. Allen
Elizabeth Dudnik
Ofer Rotem
Noga Kurman
Omer Gal
Hiba Reches
Alona Zer
author_facet Michal Sternschuss
Nir Peled
Aaron M. Allen
Elizabeth Dudnik
Ofer Rotem
Noga Kurman
Omer Gal
Hiba Reches
Alona Zer
author_sort Michal Sternschuss
collection DOAJ
description Anti‐PD‐1/PD‐L1 agents play a crucial part in the treatment of non‐small cell cancer (NSCLC) demonstrating improved overall response rate (ORR) and overall survival (OS). Recent studies evaluating combination treatment with anti‐PD‐1 and anti‐CTLA‐4 suggests improved outcome but also increased toxicity. Evidence is scarce regarding subsequent treatment with immune checkpoint inhibitors (ICPI) after progression on anti‐PD‐1/PD‐L1. A total of 15 patients were treated with a combination of anti‐PD1 agent and ipilimumab after confirmed progression of disease on anti‐PD1/PDL1 alone during 2017. Clinical data were retrieved retrospectively. Disease control rate (DCR) was defined as partial response (PR) or stable disease (SD). The overall DCR was 33.3% (n = 5); two patients with PR and three patients with SD, three of whom had prior documented disease control on anti‐PD1. The immune‐related adverse event (irAE) rate was 40% (n = 6); two patients had grade 3 AE and one patient died of pneumonitis. While the median time to progression was two months (range 0.5–16), four of the five patients with PR/SD experienced durable benefit for 8–16 months. This small retrospective cohort of heavily pretreated unselected patients suggests ipilimumab might reboost the immune response in patients with advanced NSCLC following progression of disease on anti‐PD1 therapy, while delaying exposure to the higher toxicity rates associated with upfront combination therapy. This strategy should be explored prospectively.
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spelling doaj.art-b2bfa9d7745e42549862340cfd51a3d12022-12-21T23:52:07ZengWileyThoracic Cancer1759-77061759-77142020-08-011182331233410.1111/1759-7714.13502Can Ipilimumab restore immune response in advanced NSCLC after progression on anti‐PD‐1/PD‐L1 agents?Michal Sternschuss0Nir Peled1Aaron M. Allen2Elizabeth Dudnik3Ofer Rotem4Noga Kurman5Omer Gal6Hiba Reches7Alona Zer8Davidoff Cancer Center Rabin Medical Center Petah Tikva IsraelThe Legacy Heritage Oncology Center Soroka Medical Center Beer‐Sheva IsraelDavidoff Cancer Center Rabin Medical Center Petah Tikva IsraelDavidoff Cancer Center Rabin Medical Center Petah Tikva IsraelDavidoff Cancer Center Rabin Medical Center Petah Tikva IsraelDavidoff Cancer Center Rabin Medical Center Petah Tikva IsraelDavidoff Cancer Center Rabin Medical Center Petah Tikva IsraelDavidoff Cancer Center Rabin Medical Center Petah Tikva IsraelDavidoff Cancer Center Rabin Medical Center Petah Tikva IsraelAnti‐PD‐1/PD‐L1 agents play a crucial part in the treatment of non‐small cell cancer (NSCLC) demonstrating improved overall response rate (ORR) and overall survival (OS). Recent studies evaluating combination treatment with anti‐PD‐1 and anti‐CTLA‐4 suggests improved outcome but also increased toxicity. Evidence is scarce regarding subsequent treatment with immune checkpoint inhibitors (ICPI) after progression on anti‐PD‐1/PD‐L1. A total of 15 patients were treated with a combination of anti‐PD1 agent and ipilimumab after confirmed progression of disease on anti‐PD1/PDL1 alone during 2017. Clinical data were retrieved retrospectively. Disease control rate (DCR) was defined as partial response (PR) or stable disease (SD). The overall DCR was 33.3% (n = 5); two patients with PR and three patients with SD, three of whom had prior documented disease control on anti‐PD1. The immune‐related adverse event (irAE) rate was 40% (n = 6); two patients had grade 3 AE and one patient died of pneumonitis. While the median time to progression was two months (range 0.5–16), four of the five patients with PR/SD experienced durable benefit for 8–16 months. This small retrospective cohort of heavily pretreated unselected patients suggests ipilimumab might reboost the immune response in patients with advanced NSCLC following progression of disease on anti‐PD1 therapy, while delaying exposure to the higher toxicity rates associated with upfront combination therapy. This strategy should be explored prospectively.https://doi.org/10.1111/1759-7714.13502Immune‐related adverse eventsipilimumabnivolumabNSCLC
spellingShingle Michal Sternschuss
Nir Peled
Aaron M. Allen
Elizabeth Dudnik
Ofer Rotem
Noga Kurman
Omer Gal
Hiba Reches
Alona Zer
Can Ipilimumab restore immune response in advanced NSCLC after progression on anti‐PD‐1/PD‐L1 agents?
Thoracic Cancer
Immune‐related adverse events
ipilimumab
nivolumab
NSCLC
title Can Ipilimumab restore immune response in advanced NSCLC after progression on anti‐PD‐1/PD‐L1 agents?
title_full Can Ipilimumab restore immune response in advanced NSCLC after progression on anti‐PD‐1/PD‐L1 agents?
title_fullStr Can Ipilimumab restore immune response in advanced NSCLC after progression on anti‐PD‐1/PD‐L1 agents?
title_full_unstemmed Can Ipilimumab restore immune response in advanced NSCLC after progression on anti‐PD‐1/PD‐L1 agents?
title_short Can Ipilimumab restore immune response in advanced NSCLC after progression on anti‐PD‐1/PD‐L1 agents?
title_sort can ipilimumab restore immune response in advanced nsclc after progression on anti pd 1 pd l1 agents
topic Immune‐related adverse events
ipilimumab
nivolumab
NSCLC
url https://doi.org/10.1111/1759-7714.13502
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