Combination of HER2-targeted agents with immune checkpoint inhibitors in the treatment of HER2-positive breast cancer.

INTRODUCTION: Human epidermal growth factor receptor 2 (HER2)-positive breast cancers account for approximately 15 to 20% of breast cancer diagnoses. Historically, HER2-positive breast cancers had been associated with poorer prognosis. The addition of HER2-targeted agents to treatment regimens has significantly improved outcomes for patients with HER2-positive breast cancer. Despite this, relapses continue to occur in about 20% of patients. Newer therapeutic strategies are needed. The role of immunotherapy in the treatment of HER2-positive breast cancer is currently under clinical investigation. AREAS COVERED: This article will focus on the clinical trial data evaluating immune checkpoint inhibitors, including pembrolizumab, atezolizumab, avelumab, durvalumab, and nivolumab in the treatment of HER2-positive breast cancer. EXPERT OPINION: The incorporation of immunotherapy in the treatment of HER2-positive breast cancer is a reasonable strategy. Clinical trials of checkpoint inhibitors with HER2-targeted agents show clinical activity in HER2-positive breast cancer tumors that are programmed cell death-ligand 1 (PD-L1) positive and also when used as an earlier line of therapy in the metastatic setting. Treatment of HER2-positive breast cancer with immunotherapy and HER2-targeted agents warrants continued clinical investigation.

Thromboembolism Incidence and Risk Factors in Multiple Myeloma After First Exposure to Immunomodulatory Drug-Based Regimens.

BACKGROUND: We evaluated time to thromboembolism (TE) and risk factors in multiple myeloma (MM) patients after first exposure to immunomodulatory therapy, stratified by thromboprophylaxis. PATIENTS AND METHODS: We retrospectively analyzed adult MM patients who received immunomodulatory therapy with or without dexamethasone between February 2012 and October 2017. Thromboprophylaxis included aspirin, anticoagulants (low-molecular-weight heparin, direct oral anticoagulants, or warfarin), or none. Primary endpoint was time to on-treatment TE by thromboprophylaxis type. Time to TE using death as a competing risk censored at 12 months was used in univariate and multivariable analyses to identify risk factors. RESULTS: Of 485 evaluable patients, 57% were white and 36% African American; median age was 66. Most received lenalidomide (97.5%) and dexamethasone (90%). Half presented with ≥ 1 comorbidities. Sixty-nine had no documented receipt of prophylaxis, 357 aspirin, and 59 anticoagulation. More patients receiving anticoagulants had ≥ 1 comorbidities compared to aspirin or no-prophylaxis groups (P < .001). There was no difference in 12-month estimated cumulative incidence of TE (7.3%; 95% confidence interval, 5.2-9.9) between thromboprophylaxis groups (none 4.4%, aspirin 8.5%, anticoagulant 3.4%) (P = .24). In multivariable analyses, male sex (hazard ratio, 2.50; 95% confidence interval, 1.21-5.17; P = .014) and presence of any comorbidity (hazard ratio, 2.35; 95% confidence interval, 1.17-4.73; P = .016) were associated with TE incidence; thromboprophylaxis type was not (P = .12). CONCLUSION: Male sex and presence of any comorbidity were associated with time to TE. There were no differences in TE incidence between thromboprophylaxis groups despite a higher proportion of those in the anticoagulant group having ≥ 1 comorbidities.