How to manage patients with corticosteroids in oncology in the era of immunotherapy?

Aldea, Mihaela; Orillard, Émeline; Mansi, Laura; Marabelle, Aurélien; Scotté, Florian; Lambotte, Olivier; Michot, Jean‐Marie

doi:10.1016/j.ejca.2020.09.032

Cited by 65 publications

(97 citation statements)

References 79 publications

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“…This recommendation was based on reports in the literature that this approach is feasible 13 and because of potential dampening of the activity of immunotherapy when administered concomitantly with steroids. 14 Treatment was continued until disease progression according to RECIST version 1.1, unacceptable toxicity or consent withdrawal.…”

Section: Methodsmentioning

confidence: 99%

Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer

Miles¹,

Gligorov²,

André³

et al. 2021

Annals of Oncology

457

289

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Background: In the phase III IMpassion130 trial, combining atezolizumab with first-line nanoparticle albumin-boundpaclitaxel for advanced triple-negative breast cancer (aTNBC) showed a statistically significant progression-free survival (PFS) benefit in the intention-to-treat (ITT) and programmed death-ligand 1 (PD-L1)-positive populations, and a clinically meaningful overall survival (OS) effect in PD-L1-positive aTNBC. The phase III KEYNOTE-355 trial adding pembrolizumab to chemotherapy for aTNBC showed similar PFS effects. IMpassion131 evaluated first-line atezolizumabepaclitaxel in aTNBC. Patients and methods: Eligible patients [no prior systemic therapy or 12 months since (neo)adjuvant chemotherapy] were randomised 2:1 to atezolizumab 840 mg or placebo (days 1, 15), both with paclitaxel 90 mg/m 2 (days 1, 8, 15), every 28 days until disease progression or unacceptable toxicity. Stratification factors were tumour PD-L1 status, prior taxane, liver metastases and geographical region. The primary endpoint was investigator-assessed PFS, tested hierarchically first in the PD-L1-positive [immune cell expression 1%, VENTANA PD-L1 (SP142) assay] population, and then in the ITT population. OS was a secondary endpoint. Results: Of 651 randomised patients, 45% had PD-L1-positive aTNBC. At the primary PFS analysis, adding atezolizumab to paclitaxel did not improve investigator-assessed PFS in the PD-L1-positive population [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.60-1.12; P ¼ 0.20; median PFS 6.0 months with atezolizumabepaclitaxel versus 5.7 months with placeboepaclitaxel]. In the PD-L1-positive population, atezolizumabepaclitaxel was associated with more favourable unconfirmed best overall response rate (63% versus 55% with placeboepaclitaxel) and median duration of response (7.2 versus 5.5 months, respectively). Final OS results showed no difference between arms (HR 1.11, 95% CI 0.76-1.64; median 22.1 months with atezolizumabepaclitaxel versus 28.3 months with placeboe paclitaxel in the PD-L1-positive population). Results in the ITT population were consistent with the PD-L1-positive population. The safety profile was consistent with known effects of each study drug. Conclusion: Combining atezolizumab with paclitaxel did not improve PFS or OS versus paclitaxel alone. ClinicalTrials.gov: NCT03125902.

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Section: Methodsmentioning

confidence: 99%

Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer

Miles¹,

Gligorov²,

André³

et al. 2021

Annals of Oncology

457

289

View full text Add to dashboard Cite

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“…It can also lead to hypokalemia, skeletal dysfunction, mood disorders, and adrenal insufficiency. Prior to starting a rehabilitation program, the dosage and duration for corticosteroids should be reviewed with the goal of using the lowest dose and for the shortest period [ 55 ].…”

Section: Laboratory Abnormalitiesmentioning

confidence: 99%

Safety, Precautions, and Modalities in Cancer Rehabilitation: an Updated Review

Zheng

Mixon

McLarney

2021

Curr Phys Med Rehabil Rep

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Purpose of Review Providing rehabilitation to patients with cancer can be challenging due to the medical complexity associated with the illness and its treatments. This article provides the reader with a summary of frequently encountered medical conditions in the cancer population and associated safety considerations and precautions. An update on treatment modalities commonly used for symptom management is also presented. Recent Findings Cancer and cancer treatments can cause changes in multiple organ systems. Special considerations and precautions are necessary to provide safe and effective rehabilitation. Physical modalities can be used as monotherapy or adjunct to treatment for common cancer-related side effects with recent studies noting benefit with a variety of modalities. Summary Detailed assessment of the cancer patient is necessary before implementing a rehabilitation program. Understanding cancer and side effects of treatments, including newer options, are necessary to provide safe care.

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“…Dexamethasone (Dex) is a glucocorticosteroid (Figure 1) and exhibits pleotropic effects [45] on cells. Corticosteroids such as Dex are commonly used in cancer chemotherapy to relieve dyspnea, bowel obstruction, spinal cord compression, and pain from bone metastases and neurological symptoms [46].…”

Section: Dexamethasonementioning

confidence: 99%

“…Corticosteroids are also often used to control immune-related adverse events (irAEs) such as autoimmune or allergic reactions that can emerge as a consequence of immune checkpoint blockade therapies [45,50], although the mechanism(s) by which these molecules impact cellular immunity is not well understood [25]. Clearly, corticosteroids do have potent regulatory effects on inflammation and T cell activity (Table 1).…”

Section: Dexamethasonementioning

confidence: 99%

The Impact of Induction Regimes on Immune Responses in Patients with Multiple Myeloma

Firer

Shapira

Luboshits

2021

Cancers

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Current standard frontline therapy for newly diagnosed patients with multiple myeloma (NDMM) involves induction therapy, autologous stem cell transplantation (ASCT), and maintenance therapy. Major efforts are underway to understand the biological and the clinical impacts of each stage of the treatment protocols on overall survival statistics. The most routinely used drugs in the pre-ASCT “induction” regime have different mechanisms of action and are employed either as monotherapies or in various combinations. Aside from their direct effects on cancer cell mortality, these drugs are also known to have varying effects on immune cell functionality. The question remains as to how induction therapy impacts post-ASCT immune reconstitution and anti-tumor immune responses. This review provides an update on the known immune effects of melphalan, dexamethasone, lenalidomide, and bortezomib commonly used in the induction phase of MM therapy. By analyzing the actions of each individual drug on the immune system, we suggest it might be possible to leverage their effects to rationally devise more effective induction regimes. Given the genetic heterogeneity between myeloma patients, it may also be possible to identify subgroups of patients for whom particular induction drug combinations would be more appropriate.

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How to manage patients with corticosteroids in oncology in the era of immunotherapy?

Cited by 65 publications

References 79 publications

Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer

Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer

Safety, Precautions, and Modalities in Cancer Rehabilitation: an Updated Review

The Impact of Induction Regimes on Immune Responses in Patients with Multiple Myeloma

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