Rapid response of metastatic cutaneous squamous cell carcinoma to pembrolizumab in a patient with xeroderma pigmentosum: Case report and review of the literature

Deinlein, Teresa; Lax, Sigurd; Schwarz, Thomas; Giuffrida, Roberta; Schmid‐Zalaudek, Karin; Zalaudek, Iris

doi:10.1016/j.ejca.2017.06.022

Cited by 44 publications

(39 citation statements)

References 7 publications

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“…Tumors harboring other defects in DNA repair that can give rise to high TMB, such as tumors arising in patients with xeroderma pigmentosa, may also be associated with response to ICB (Deinlein et al 2017). Tumors with underlying defects in homologous recombination-mediated DNA repair, such as those with mutations in BRCA1 and BRCA2, do not have a very high burden of small nonsynonymous mutations, but do have a large number of structural variations and genomic rearrangements that are not well captured by exome sequencing but may be immunogenic (Davies et al 2017, Yang et al 2019.…”

Section: Other Repair Defectsmentioning

confidence: 99%

Biomarkers for Response to Immune Checkpoint Blockade

Ganesan

Mehnert²

2020

Annu. Rev. Cancer Biol.

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Immune checkpoint blockade (ICB) has significant clinical activity in diverse cancer classes and can induce durable remissions in even refractory advanced disease. However, only a minority of cancer patients treated with ICB have long-term benefits, and ICB treatment is associated with significant, potentially life-threatening, autoimmune side effects. There is a great need to develop biomarkers of response to guide patient selection to maximize the chance of benefit and prevent unnecessary toxicity, and current biomarkers do not have optimal positive or negative predictive value. A variety of potential biomarkers are currently being developed, including those based on assessment of checkpoint protein expression, evaluation of tumor-intrinsic features including mutation burden and viral infection, evaluation of features of the tumor immune microenvironment including nature of immune cell infiltration, and features of the host such as composition of the gut microbiome. Better understanding of the underlying fundamental mechanisms of immune response and resistance to ICB, along with the use of complementary assays that interrogate distinct features of the tumor, the tumor microenvironment, and host immune system, will allow more precise use of these therapies to optimize patient outcomes.

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Section: Other Repair Defectsmentioning

confidence: 99%

Biomarkers for Response to Immune Checkpoint Blockade

Ganesan

Mehnert²

2020

Annu. Rev. Cancer Biol.

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“…Recommended doses are 3 mg for kilograms of weight every 3 weeks as intravenous (iv) infusion for a period of 30 minutes. Among the different PD-1 inhibitors, the number of patients treated is the widest, about 28 reported in the literature (Assam et al, 2016;Borradori et al, 2016;Chang et al, 2016;Degache et al, 2018;Deinlein et al, 2017;Ferrarotto, 2017;Lipson et al, 2016;Ravulapati et al, 2017;Stevenson et al, 2017;Tran et al, 2017;Winkler et al, 2017;Zalaudek et al, 2019), excluding the ongoing trials in Phase I and II (Licitra et al, 2017;Kudchadkar et al, 2018;Maubec et al, 2019). Although the larger number of reported cases, responses data are not enough and in addition with short period of follow-up.…”

Section: Pembrolizumabmentioning

confidence: 99%

“…While Stevenson et al () (LE 4 following Oxford CEBM Levels of Evidence) showed the abundant expression of PD‐1 in cSCC, mainly in cases with perineural invasion. Deinlein et al () (LE 4 following Oxford CEBM Levels of Evidence) proposed for the first time pembrolizumab in Stage IV cSCC in patient affected by Xeroderma Pigmentosum (XP), a genomic syndrome due to loss of function of nucleotide excision repair pathway, causing high sensitivity to ultravaiolet (UV) radiation. In this case, a rapid complete response after only three cycles was evidenced.…”

Section: Introductionmentioning

confidence: 99%

Pattern of response of unresectable and metastatic cutaneous squamous cell carcinoma to programmed death‐1 inhibitors: A review of the literature

Corneli

Conforti

Retrosi

et al. 2020

Dermatologic Therapy

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Cutaneous squamous cell carcinoma (cSCC) is the second most frequent nonmelanoma skin cancer (NMSC). The majority of in situ cSCC [cSCC (Tis)] can be cured surgically, while local advanced and metastatic ones require other treatments, but there are no therapies approved by U.S. Food and Drug Administration (FDA). Available treatments for these stages included radiotherapy, chemotherapy as cisplatin, but responses to these treatments are usually of short duration. Programmed death‐1 (PD‐1) inhibitors (pembrolizumab, nivolumab, and cemiplimab) are an innovative immunologic treatment that now has been shown to be useful for the treatment of advanced cSCC. Nowadays, data about the response rate with the use of PD‐1 inhibitors in cSCC are still few and, especially, the duration of the response after the start of treatment is short. Moreover, the number of cases is too small to express the beneficial effects of these treatments, although most data reported in the literature show quite good response rates. This review focused on some of the studies and associated results through an interesting research on search engines of all the cases about these systemic drugs, analyzing effects and side effects, and the research has been conducted considering published cases since March 2016 to October 2019.

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“…In a preclinical mouse model, PD-1-PDL-1 activation contributed to the development of cSCC [6]. Moreover, the efficacy of anti-PD-1 mAb in patients with cSCC has been reported recently in a few case series [7][8][9][10][11][12][13][14][15][16][17] and in a Phase 1-2 trial with cemiplimab [18]. Herein, we report for the first time two complete responses (CR), allowing treatment discontinuation without recurrence to date, in a series of four patients with advanced cSCC treated with pembrolizumab and concurrent hypofractionated radiotherapy.…”

mentioning

confidence: 99%