Pityriasis rubra pilaris-like erythroderma secondary to phosphoinositide 3-kinase inhibition

Dewan, Anna K.; Sowerby, Laura; Jadeja, Saagar; Lian, Christine G.; Wen, Patrick Y.; Brown, Jennifer R.; Fisher, David C.; LeBoeuf, Nicole R.

doi:10.1111/ced.13608

Cited by 13 publications

(19 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cutaneous toxicities can usually be managed without stopping the drug, taking weeks to months to resolve. This delay from drug introduction to the development of cutaneous symptoms and the slow resolution is consistent with other dermatologic immune‐related adverse events because of unregulated T‐cell activation 11 . In contrast, in our two cases, the cutaneous lesions disappeared in two weeks after withdrawing the drugs.…”

Section: Discussionsupporting

confidence: 89%

“…Class I PI3K is the most frequently targeted class in cancer treatment 11 . It is a heterodimer composed of a regulatory and a catalytic subunit.…”

Section: Discussionmentioning

confidence: 99%

“…It is a heterodimer composed of a regulatory and a catalytic subunit. The latter has four distinct isoforms with diverse tissue distribution, activity and toxic effect profile 8,11 . The α and β isoforms are expressed ubiquitously and regulate a wide range of physiological processes 8 .…”

Section: Discussionmentioning

confidence: 99%

“…The γ and δ isoforms are mainly expressed on leukocytes 8 . PI3Kδ blockade is associated with immunomodulation, leading to decreased of regulatory T‐cell function and increased effector T‐cell activity 11 …”

Section: Discussionmentioning

confidence: 99%

“…The main adverse effects reported in trials of PI3K inhibitors are lung, liver, hematologic, and cutaneous toxic effects 8 . Skin reactions are noted in 23% to 58% of patients 11 . The most frequent ones are maculopapular eruption, pruritus, and dry skin, 8 but most trials lack further descriptive specificity.…”

Section: Discussionmentioning

confidence: 99%

See 4 more Smart Citations

Cutaneous eruption with reactive endothelial atypia due to emerging targeted cancer therapies: Report of two cases with clinico‐pathologic correlation

et al. 2021

View full text Add to dashboard Cite

Targeted anticancer therapy is being used with greater frequency and dermatologic toxicities are among the most frequent adverse events of these drugs. However, histopathological features of these adverse events are not yet well characterized. We present two cases of clinically different cutaneous toxicities on two patients with hematologic neoplasia. They were treated with different drugs and in both cases medications shared inhibition of PI3K as mechanism of action. The skin biopsy specimen showed endothelial cell atypia with large nuclei and mitotic figures. To the best of our knowledge, no other cases with these striking histopathologic findings have been reported with PI3K inhibitors or other anticancer targeted therapy.

show abstract

Section: Discussionsupporting

confidence: 89%

“…Class I PI3K is the most frequently targeted class in cancer treatment 11 . It is a heterodimer composed of a regulatory and a catalytic subunit.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Cutaneous eruption with reactive endothelial atypia due to emerging targeted cancer therapies: Report of two cases with clinico‐pathologic correlation

et al. 2021

View full text Add to dashboard Cite

show abstract

Incidence of Cutaneous Adverse Events With Phosphoinositide 3-Kinase Inhibitors as Adjuvant Therapy in Patients With Cancer

et al. 2022

View full text Add to dashboard Cite

ImportanceThe phosphoinositide 3-kinase (PI3K) pathway is among the most frequently activated pathways in human cancers. As the use of PI3K inhibitors for cancer treatment grows, there is increasing need for understanding the cutaneous effects associated with these therapies.ObjectiveTo systematically review the published literature reporting incidence of cutaneous adverse events with PI3K inhibitors and to provide pooled incidence estimates using meta-analysis.Data SourcesThis systematic review and meta-analysis was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. The literature search concerned entries through September 2021 in the following sources: PubMed, Cochrane registry, ClinicalTrials.gov, and evidence from the NHS UK and Trip medical database. To analyze PI3K inhibitors’ cutaneous adverse events incidence, only randomized clinical trials (RCTs) were considered. The search strategy used the following keywords: (prevalence OR incidence OR epidemiology) and (phosphoinositide 3 kinase inhibitors OR PI3K inhibitors). No language restriction was applied. Analysis was conducted on July 1, 2022.Study SelectionStudies included phase 2 and phase 3 RCTs that reported incidence of cutaneous adverse events associated with use of PI3K inhibitors.Data Extraction and MeasuresData extracted included sex, medication name and class, sample size, rash incidence, and grade. The bias risk was assessed by the Cochrane tool for risk of bias assessment in RCTs.Main Outcomes and MeasuresThe primary outcome was incidence of PI3K inhibitor cutaneous adverse events (with 95% CIs) among the overall population and among subgroups. Between-study heterogeneity was assessed using the I2 statistic.ResultsThe analysis found the incidence of PI3K inhibitor cutaneous events of any grade to be 29.30% in the intervention group, translating to a pooled odds ratio (OR) for incidence of cutaneous adverse events of any grades of 2.55 (95% CI, 1.74-3.75). Incidence of severe grade (grade ≥3) of rash in the intervention group was estimated to be 6.95%, yielding a pooled Peto OR of 4.64 (95% CI, 2.70-7.97). Subgroup analyses revealed that the incidence of severe cutaneous adverse events (grade ≥3) was higher with the use of Pan-class-1 PI3K inhibitors (OR, 6.67; 95% CI, 4.28-10.38) than isoform-selective PI3K inhibitors (OR, 6.37; 95% CI, 3.25-12.48).Conclusions and RelevanceThis systematic review and meta-analysis identified an overall incidence of PI3K inhibitor cutaneous adverse events of any grade to be 29.30% with a pooled OR of 2.55; (95% CI, 1.74-3.75). These findings clarify the risk of cutaneous adverse events associated with this important class of anticancer therapies.

show abstract

Development and safety of PI3K inhibitors in cancer

Chen

et al. 2023

Arch Toxicol

View full text Add to dashboard Cite

The phosphatidylinositol 3-kinase (PI3K) signalling pathway regulates cell survival, proliferation, migration, metabolism and other vital cellular life processes. In addition, activation of the PI3K signalling pathway is important for cancer development. As a result, a variety of PI3K inhibitors have been clinically developed to treat malignancies. Although several PI3K inhibitors have received approval from the Food and Drug Administration (FDA) for significant antitumour activity, frequent and severe adverse effects have greatly limited their clinical application. These toxicities are mostly on-target and immune-mediated; nevertheless, the underlying mechanisms are still unclear. Current management usually involves intervention through symptomatic treatment, with discontinuation if toxicity persists. Therefore, it is necessary to comprehensively understand these adverse events and ensure the clinical safety application of PI3K inhibitors by establishing the most effective management guidelines, appropriate intermittent dosing regimens and new combination administration. Here, the focus is on the development of PI3K inhibitors in cancer therapy, with particular emphasis on isoform-specific PI3K inhibitors. The most common adverse effects of PI3K inhibitors are also covered, as well as potential mechanisms and management approaches.

show abstract

Pityriasis rubra pilaris-like erythroderma secondary to phosphoinositide 3-kinase inhibition

Abstract: PRP-like cutaneous eruptions may develop secondary to PI3K inhibition. Early dermatological evaluation of cutaneous toxicities to PI3K inhibitors as well as rapid initiation of disease-specific treatments may help keep patients on life-prolonging anti-cancer therapies.

Cited by 13 publications

References 19 publications

Cutaneous eruption with reactive endothelial atypia due to emerging targeted cancer therapies: Report of two cases with clinico‐pathologic correlation

Cutaneous eruption with reactive endothelial atypia due to emerging targeted cancer therapies: Report of two cases with clinico‐pathologic correlation

Incidence of Cutaneous Adverse Events With Phosphoinositide 3-Kinase Inhibitors as Adjuvant Therapy in Patients With Cancer

Development and safety of PI3K inhibitors in cancer

Contact Info

Product

Resources

About