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

Abstract

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.

Translational perspectives to treat Epidermolysis bullosa—Where do we stand?

“…[69,70] Clinical trials are currently underway to assess anti-tumor activity of rigosertib (NCT03786237, NCT04177498), a serine/ threonine-protein kinase (Polo-like Kinase 1) inhibitor that leads to apoptosis specifically in RDEB cancer cells, [71] as well as of the programmed cell death protein 1 (PD-1) inhibitors nivolumab and cemiplimab. [72] While the latter have become a standard treatment for advanced non-EB SCC, administration in EB patients is only anecdotally reported. [73][74][75] Thus, their therapeutic and immunomodulatory impact on EB hitherto remains largely unknown, including potentially disadvantageous effects on barrier integrity, local and systemic inflammatory state, microbial burden and susceptibility to skin infections.…”

“…• symptom-relieving therapies, targeting distinct symptoms such as scarring (TGF-β, TSP1 [104] and losartan [31,105 ), itch (dupilumab [31] ) and skin cancer (rigosertib, [7] pembrolizumab [72] and nivolumab (EudraCT 2016-002811-16));…”

“… gene replacement therapies, with either transplantation of sheets or topical application of emulgated/dispersed molecularly corrected cells/tissue (or corrective agents) onto sites of chronic wounding; topical applications, which offer vulnerable EB cohorts increased tolerability and feasibility and are of particular value for treating mucosal lesions and poorly accessible skin areas that are infeasible or challenging for skin grafting, like interdigital/intertriginous areas and face; skin grafting that is mainly restricted to sites of chronic and/or large blistering erosions to improve quality of life by reduction of itch, pain, inflammation, body fluid and protein loss while strengthening microbial defense and preventing cancer development in high‐risk long‐standing wounds; systemic and local immune modulation, for example iv stem cell infusions or ideally oral or liquid maintenance (immunomodulatory) therapies as booster, and topical agents like diacerein, calcipotriol; symptom‐relieving therapies, targeting distinct symptoms such as scarring (TGF‐β, TSP1 [ 104 ] and losartan [ 31,105 ), itch (dupilumab [ 31 ] ) and skin cancer (rigosertib, [ 7 ] pembrolizumab [ 72 ] and nivolumab (EudraCT 2016‐002811‐16)); strategies for microbial surveillance (eg glucose peroxidase‐lactoperoxidase gel; hydrofiber dressings; quorum sensing), [ 15 ] and last but not least, various combinations of these approaches, applied in a complementary or synergistic fashion. …”

Diagnosis and treatment of melanoma bone metastasis: A multidisciplinary approach

“…A study shows that patients who develop cutaneous adverse events had a better overall survival. 25,26 The most serious toxicity is pneumonitis with possible fatal outcome. Adverse events occur in 6% of patients.…”

“…There are also cases of cutaneous adverse events: skin eruptions vitiligo and isolated pruritus. A study shows that patients who develop cutaneous adverse events had a better overall survival 25,26 . The most serious toxicity is pneumonitis with possible fatal outcome.…”