Survival, treatment patterns, and costs of HER2+ metastatic breast cancer patients in Ontario between 2005 to 2020.

BACKGROUND: To enable the integration of novel therapies, it is critical to understand current long-term outcomes in HER2-positive metastatic breast cancer (mBC), including survival, treatment patterns, and costs. We sought to define these outcomes among patients with mBC in Ontario. METHODS: We conducted a retrospective population-level study in Ontario women diagnosed with breast cancer of any stage between January 1, 2005 and December 31, 2019, with follow-up until December 31, 2020. HER2-positivity was based on receipt of a HER2-targeted therapy (HER2-TT) in the first line (1L) metastatic setting. Administrative databases at ICES were used to assess outcomes. RESULTS: In Ontario, 2557 patients were diagnosed with mBC and received a HER2-TT, and of these 1606 were diagnosed with early-stage (stage I-III) that became metastatic (recurrent), while 951 were diagnosed with late stage/de novo mBC (stage IV). The average age of all patients was 54.8 years ± 12.7 years. Treatment regimens that included pertuzumab and trastuzumab (cohort name: pert_tras) were the most frequently used HER2-TT for 1L mBC (51.4%), while T-DM1 was the most frequent therapy (87.5%) in second line (2L). The median overall survival (mOS) from initiation of 1L pert_tras was not reached, whereas mOS from initiation of T-DM1 in 2L was 18.7 months. The overall mean cost per patient on pert_tras during 1L was $267,282. The main cost drivers were the cost of systemic therapy, followed by cancer clinic visits, with a mean cost per patient at $158,961 and $73,882, respectively. CONCLUSION: The baseline characteristics and treatment patterns for patients who received HER2-TT in our study align with previously reported results. However, the mOS observed for 2L T-DM1 was shorter than that found in pivotal, clinical trial literature. As expected, anti-cancer systemic therapy costs were the main contributor to the over quarter-million dollar mean cost per patient on pert_tras in 1L.

Immunotherapy with peptides.

Specific allergen immunotherapy is clinically effective and disease modifying. It has a duration of effect that exceeds the treatment period and prevents both the progression of allergic rhinitis to asthma and the acquisition of new allergic sensitizations. However, immunotherapy is associated with a high frequency of adverse events related to the allergenicity of vaccines. Allergenicity is conferred by the presence of intact B-cell epitopes that crosslink allergen-specific IgE on effector cells. The use of linear peptide sequences representing fragments of the native allergen is one approach to reduce allergenicity. Preclinical models of peptide immunotherapy have demonstrated efficacy in both autoimmunity and allergy. Translation of this technology into the clinic has gained momentum in recent years based on encouraging results from early clinical trials. To date, efforts have focused on two major allergens, but vaccines to a broader range of molecules are currently in clinical development. Mechanistically, peptide immunotherapy appears to work through the induction of adaptive, allergen-specific regulatory T cells that secrete the immunoregulatory cytokine IL-10. There is also evidence that peptide immunotherapy targeting allergen-specific T cells can indirectly modulate allergen-specific B-cell responses. Peptide immunotherapy may provide a safe and efficacious alternative to conventional subcutaneous and/or sublingual approaches using native allergen preparations.

Amelioration of ovalbumin-induced allergic airway disease following Der p 1 peptide immunotherapy is not associated with induction of IL-35.

In the present study, we show therapeutic amelioration of established ovalbumin (OVA)-induced allergic airway disease following house dust mite (HDM) peptide therapy. Mice were sensitized and challenged with OVA and HDM protein extract (Dermatophagoides species) to induce dual allergen sensitization and allergic airway disease. Treatment of allergic mice with peptides derived from the major allergen Der p 1 suppressed OVA-induced airway hyperresponsiveness, tissue eosinophilia, and goblet cell hyperplasia upon rechallenge with allergen. Peptide treatment also suppressed OVA-specific T-cell proliferation. Resolution of airway pathophysiology was associated with a reduction in recruitment, proliferation, and effector function of T(H)2 cells and decreased interleukin (IL)-17⁺ T cells. Furthermore, peptide immunotherapy induced the regulatory cytokine IL-10 and increased the proportion of Fox p3⁺ cells among those expressing IL-10. Tolerance to OVA was not associated with increased IL-35. In conclusion, our results provide in vivo evidence for the creation of a tolerogenic environment following HDM peptide immunotherapy, leading to the therapeutic amelioration of established OVA-induced allergic airway disease.