Medicine (St Vincent's) - Research Publications
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ItemNo Preview AvailableThe Role of Systemic Therapies in the Management of Soft Tissue Sarcoma(Springer Singapore, 2021)
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ItemUpdate of Immune Therapies in Recurrent/Metastatic Head and Neck Cancer(Springer International Publishing, 2021)Abstract Since the initial reports of activity of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), investigation of the role of immune therapies has been the major focus of clinical trials in R/M HNSCC. Randomised trials initially with nivolumab and later with pembrolizumab established overall survival benefit in patients with R/M HNSCC previously treated with platinum compared to physicians choice of 2nd line therapy, and have led to regulatory approval around the world. More recently the Keynote-048 trial has compared both pembrolizumab monotherapy and pembrolizumab + platinum/5FU to the Extreme regimen of platinum/5FU/cetuximab in the first-line R/M setting. The key findings from this trial are that pembrolizumab monotherapy compared to Extreme improved overall survival in patients with PD-L1 combined positive score (CPS) ≥ 20 and ≥ 1, and that pembro/chemotherapy improved OS in CPS ≥ 20, CPS ≥ 1 and the total population. Relative to Extreme there was less toxicity in the monotherapy arm and comparable toxicity in the pembro/chemo arm. Based on this trial use of pembrolizumab as part of first-line treatment for R/M HNSCC is appropriate for the majority of patients, and represents a new standard of care. The focus has now moved to identifying combinations that may be superior to pembrolizumab monotherapy or to chemotherapy + pembrolizumab. Some of the more promising approaches under investigation in HNSCC are discussed in this chapter. In summary, immune therapies are now the cornerstone of management of R/M HNSCC with the approval of pembrolizumab in the first-line R/M setting.
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ItemBiomarkers for Immune Modulatory Treatment in Head and Neck Squamous Cell Carcinoma (HNSCC)(Springer International Publishing, 2021)Abstract Immune checkpoint inhibitors have changed the standard of care for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, only a minority of patients respond, hence the search for predictive biomarkers. Potential predictive biomarkers for immune checkpoint inhibitors discussed in this chapter include (1) Immune checkpoint ligand expression e.g., PD-L1, (2) biomarkers of a T-cell inflamed tumour microenvironment (TME) such as gene expression profiles of activated T cells, (3) biomarkers of tumour neoepitope burden such as tumour mutation burden (TMB) and (4) multidimensional quantitative techniques. At present only PD-L1 expression has been shown to have clinical utility in head and neck cancer. It enriches for populations more likely to respond, but the false positive predictive value remains high. In the pivotal Keynote−048 trial that established a role for pembrolizumab (anti-PD1) monotherapy and pembrolizumab + chemotherapy as treatment options in first-line R/M HNSCC, primary endpoints included overall survival in defined subgroups based on PD-L1 expression. In this trial the combined positive score (CPS) was used which takes into account PD-L1 expression in tumour and immune cells. Based on this trial regulatory approvals for first-line pembrolizumab in R/M HNSCC require assessment of PD-L1 expression using the CPS. Finally we discuss emerging evidence that locoregionally advanced HPV-associated oropharyngeal cancers that have high expression of CD103 positive CD8 T cells have an excellent prognosis and features that suggest increased probability of responding to anti-PD1/PD-L1, raising the possibility of incorporating these immune therapies as part of a de-escalation trial strategy.
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ItemNo Preview AvailableManagement of skin disease(Oxford University Press, 2020-03)Topical therapy of skin disease employs a vehicle (ointments, creams, lotions, gels) to deliver an active ingredient to the skin, to provide a protective barrier, or to hydrate and moisturize the skin. There are many types of topical treatments, including antipruritics, are used to relieve itching; keratolytics are used to remove hyperkeratotic skin; tars act by reducing the thickness of the epidermis; corticosteroids have anti-inflammatory and immunosuppressive effects that are useful in treating many skin disorders; calcipotriol reduces epidermal proliferation and is used in local treatment of plaque psoriasis; calcineurin inhibitors for eczema and other diseases; retinoids influence immune function and have some anti-inflammatory activity and are used in acne; immunomodulatory drugs such as imiquimod for some human papillomavirus infections, superficial basal cell carcinomas, and other diseases.
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ItemNo Preview AvailableEmerging Oral Treatments: Oral JAK Inhibitors for Alopecia Areata(CRC Press, 2021-03-19)
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ItemNo Preview AvailableEmerging Oral Treatments: Oral Minoxidil for Androgenetic Alopecia(CRC Press, 2021-03-19)