A nationwide observational study in heavily pretreated metastatic HER2-positive breast cancer patients.

BACKGROUND: Current guidelines in HER2-positive metastatic breast cancer (mBC) recommend the combination of trastuzumab and a chemotherapeutic agent for 3rd line or later treatments. This study aims to describe the treatment of HER2-positive mBC in 3rd line or later after previous treatment with T-DM1 for mBC in a real-world setting. MATERIAL AND METHODS: This observational population-based study included all women diagnosed with HER2-positive mBC in Denmark, previously treated with T-DM1 in the metastatic setting. Patients were included on the date of progression leading to initiation of 3rd line treatment if the patient had received T-DM1 in 1st or 2nd line. If the patient received T-DM1 in 3rd line or later the inclusion was based on the date of progression on T-DM1. The primary end points were overall survival (OS) and progression-free survival (PFS). RESULTS: The study included 272 women with a mean age of 59 (27-86) and a median of 3 (2-11) treatment lines prior to inclusion. At index, all patients had received T-DM1 and 167 (62%) patients had received pertuzumab in the metastatic setting. During follow-up 183 patients received chemotherapy. Of these patients, 120 received chemotherapy combined with trastuzumab, 50 received chemotherapy combined with other HER2-targeted therapy, and 13 received chemotherapy as monotherapy. The remaining 89 patients received either HER2-targeted monotherapy (41), endocrine therapy (31), experimental treatment (10), or no treatment (7). Median PFS was 5.5 months (95% CI, 4.8-6.5) and median OS was 18.5 months (95% CI, 16.2-21.3). CONCLUSION: In this real-world study, we found that patients were treated with a wide variety of anti-cancer agents with modest efficacy. However, patients in this study did not have access to newer therapies like tucatinib and T-DXd.

Disease activity and pretreatment, rather than hypogammaglobulinaemia, are major risk factors for infectious complications in patients with chronic lymphocytic leukaemia.

To identify patients at high risk of life-threatening infections, we retrospectively analysed the prevalence of infectious complications in 187 chronic lymphocytic leukaemia patients treated in our institution since 1999 and correlated them with clinical features. A questionnaire with detailed questions regarding infectious complications was mailed to patients and their general practitioners. Major infections (requiring intravenous antibiotics or inpatient treatment) were reported in 37 patients (19.8%) and minor infections (requiring oral antibiotics and outpatient treatment) in 113 patients (60.4%). Univariate analysis identified advanced disease (P = 0.02), gender (P = 0.01), duration of disease (P = 0.007), number of previous chemotherapy regimens (P < 0.001), previous therapy with purine analogues and monoclonal antibodies (P < 0.001; P = 0.019), massive splenomegaly (P = 0.03), low granulocyte count (P < 0.001), low serum immunoglobulin concentration (P = 0.005), low haemoglobin concentration (P < 0.001) and high serum lactate dehydrogenase (LDH) concentration (P < 0.001) as risk factors for major infections. In multivariable logistic regression analysis, only the number of previous chemotherapy regimens (risk ratio [RR] = 1.8; 95% confidence interval [CI] 1.2-8.0) and haemoglobin concentration (RR = 0.6; CI 0.5-0.8) remained significant for major infections. The number of previous chemotherapy regimens was the only independent risk factor for minor (RR = 7.6; CI 2.2-25.7) and varicella-zoster virus infections (RR = 2.1; CI 1.3-3.4). In untreated patients, the only risk factor for major infections was LDH concentration. Patients treated with purine analogues or autologous stem cell transplantation had a higher risk of developing viral infections. In conclusion, disease activity and pretreatment extent have a stronger impact on the risk of severe infectious complications than hypogammaglobulinaemia. Preferably, prophylactic strategies should be evaluated in patients defined by these parameters.