Cutaneous toxicity as a predictive biomarker for clinical outcome in patients receiving anticancer therapy

Rzepecki, Alexandra K.; Cheng, Haiying; McLellan, Beth N.

doi:10.1016/j.jaad.2018.04.046

Cited by 34 publications

(26 citation statements)

References 88 publications

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“…Finally, given the similar immunological basis between immune-related toxicity and the clinical bene t of ICIs, a number of recent retrospective studies have investigated the correlation between irAEs and the ICIse cacy, especially in lung cancer and melanoma that have shown positive results [20,[37][38][39] . A metaanalysis of four prospective studies in different cancers showed that any grade irAEs were associated with a higher overall response rate, but no effect on PFS was detected [11] .…”

Section: Discussionmentioning

confidence: 99%

Analysis of Toxicity Profile and Predictors of Immune Checkpoint Inhibitor-Related Adverse Events

Bai

Chen

et al. 2020

Preprint

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Background and objectiveIn recent years, a wide variety of immune checkpoint inhibitors (ICIs) is emerging and has shown long-lasting and significant efficacy in the treatment of various malignant tumors. However, about 10% of patients experience serious and even life-threatening immune-related adverse events (irAEs). Fully understanding the characteristics of toxic effects and biomarkers to predict irAEs is, therefore, of great interest. We aimed to retrospectively analyze the toxicity profile and predictors of irAEs, as well as the correlation between irAEs and clinical efficacy in patients with advanced pan-cancer who were treated with multi-type ICIs in real-world.MethodsWe retrospectively analyzed data from 105 patients with advanced pan-cancer who were treated with multi-type ICIs in the First Hospital of Jilin University from Jan 1, 2016 to Aug 1, 2020. We used logistic regression analyses to investigate associations between irAEs and clinical baseline characteristics, blood count parameters, and biochemical indicators during the treatment. Receiver-operating characteristic (ROC) curve was used to determine a cutoff value for parameters and area under the curve (AUC). Kaplan–Meier and cox multivariate regression analysis were performed to estimate the relationship of baseline characteristics and irAEs with progression-free survival (PFS) and overall survival (OS).ResultsWe found that lower relative lymphocyte count (RLC) (cutoff=0.285*10^9/L), higher albumin (ALB) (cutoff=39.05g/L) and higher absolute eosinophil count (AEC) (cutoff=0.175*10^9/L) were significantly associated with the occurrence of any irAEs, of which a higher AEC (cutoff=0.205*10^9/L) was strongly associated with skin-related irAEs (HR=0.163, p=0.004); And a higher lactate dehydrogenase (LDH) level (cutoff=237.5U/L) was an independent predictor of serious irAEs (HR=0.199, p=0.022). In the analysis of immune cell subgroup, lower absolute CD8+CD28- T cell count (HR=0.806; 95%CI: 0.643-1.011; p=0.062), a regulatory T lymphocytes, was associated with the occurrence of irAEs, although the difference was not statistically significant; And a higher percentage of CD19+ B cells were associated with the occurrence of serious irAEs and irAEs of grade ≥2 (p＜0.05). In addition, our study showed that patients with any grade irAE had a significantly better PFS (8.37 vs.3.77 months, HR=2.02, p=0.0038) and OS (24.77 vs.13.83 months, HR=1.78, p=0.029).ConclusionsThis retrospective study reported the clinical profile data of irAEs of unselected patients in the real world, and explored some parameters that may all be conventional, potentially predictable markers of the occurrence, type, or grade of irAEs in clinical practice. Evidence of a correlation between safety and efficacy may contribute to fully assess the risk-benefit ratio for patients treated with ICIs.

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Section: Discussionmentioning

confidence: 99%

Analysis of Toxicity Profile and Predictors of Immune Checkpoint Inhibitor-Related Adverse Events

Bai

Chen

et al. 2020

Preprint

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“…This apparent increased toxicity could potentially be related to the possible cutaneous effects of C, which could be reinforced by its daily radiosensitizing activity, and this could potentially be predictive for clinical outcome. 46 …”

Section: Discussionmentioning

confidence: 99%

Cisplatin plus capecitabine concomitant with intensity-modulated radiation therapy in non-metastatic anal squamous cell carcinoma: the experience of a single research cancer center

et al. 2020

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Background and Aims: The standard treatment of non-metastatic anal squamous cell carcinoma (ASCC) consists of chemotherapy with mitomycin (MMC) plus 5-fluorouracil (5FU) for 1–2 cycles concomitant with pelvic radiotherapy. Subsequent studies introduced cisplatin (CDDP) combined with 5FU, with unclear results. We evaluated the doublet capecitabine (C) and CDDP as a possible alternative to MMC-5FU regimen concomitant with intensity-modulated radiation therapy (IMRT). Patients and Methods: We carried out a retrospective study on 67 patients affected by stage I–III ASCC, treated with CDDP (60–70 mg/m2 every 21 days for two courses) plus C (825 mg/m2 twice daily for 5 days/week) chemotherapy concomitant with IMRT for curative intent. Results: At a median follow up of 41 months, the clinical complete response calculated at the 6-month time-point (6-moCR), the 6-month objective response rate and the 6-month disease control rate were 93%, 94%, and 99%, respectively. Disease-free survival rates at 1, 2, and 3 years were 89%, 87%, and 85%, while the overall survival rates at 1 and 2 years were 100% and 95%. The colostomy-free survival rates were 90% at 1 year and 88% at 2 years. Grade 3–4 acute adverse events were reported in 61% of patients; predominantly skin toxicity (46%) and limited hematological toxicity (12%). Conclusion: In this retrospective study, chemotherapy with C plus CDDP concomitant with IMRT proved safe and effective, and may represent a possible alternative option to standard MMC-containing regimen for curative intent.

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“…In LC, early development of immune toxicity and low-grade toxicity were correlated with a better response to immunotherapy and a survival benefit as well as endocrine toxicity [ 49 , 50 , 51 , 52 ] Regarding skin toxicity, the data are controversial. Since skin irAEs include various types of skin disorders, the association of each skin irAE with outcome may vary [ 53 ].…”

Section: Tmb From Great Expectationmentioning

confidence: 99%

From Tumor Mutational Burden to Blood T Cell Receptor: Looking for the Best Predictive Biomarker in Lung Cancer Treated with Immunotherapy

Sesma

Pardo

Cruellas

et al. 2020

Cancers

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Despite therapeutic advances, lung cancer (LC) is one of the leading causes of cancer morbidity and mortality worldwide. Recently, the treatment of advanced LC has experienced important changes in survival benefit due to immune checkpoint inhibitors (ICIs). However, overall response rates (ORR) remain low in unselected patients and a large proportion of patients undergo disease progression in the first weeks of treatment. Therefore, there is a need of biomarkers to identify patients who will benefit from ICIs. The programmed cell death ligand 1 (PD-L1) expression has been the first biomarker developed. However, its use as a robust predictive biomarker has been limited due to the variability of techniques used, with different antibodies and thresholds. In this context, tumor mutational burden (TMB) has emerged as an additional powerful biomarker based on the observation of successful response to ICIs in solid tumors with high TMB. TMB can be defined as the total number of nonsynonymous mutations per DNA megabases being a mechanism generating neoantigens conditioning the tumor immunogenicity and response to ICIs. However, the latest data provide conflicting results regarding its role as a biomarker. Moreover, considering the results of the recent data, the use of peripheral blood T cell receptor (TCR) repertoire could be a new predictive biomarker. This review summarises recent findings describing the clinical utility of TMB and TCRβ (TCRB) and concludes that immune, neontigen, and checkpoint targeted variables are required in combination for accurately identifying patients who most likely will benefit of ICIs.

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Cutaneous toxicity as a predictive biomarker for clinical outcome in patients receiving anticancer therapy

Cited by 34 publications

References 88 publications

Analysis of Toxicity Profile and Predictors of Immune Checkpoint Inhibitor-Related Adverse Events

Analysis of Toxicity Profile and Predictors of Immune Checkpoint Inhibitor-Related Adverse Events

Cisplatin plus capecitabine concomitant with intensity-modulated radiation therapy in non-metastatic anal squamous cell carcinoma: the experience of a single research cancer center

From Tumor Mutational Burden to Blood T Cell Receptor: Looking for the Best Predictive Biomarker in Lung Cancer Treated with Immunotherapy

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