Sorafenib is the only currently approved systemic therapy for advanced hepatocellular carcinoma (HCC). We aimed to evaluate the safety and efficacy of sorafenib therapy in patients with HCC under real-life conditions regarding patient, tumor characteristics, and any adverse events at study entry and at follow-up visits every 2 to 4 months. The current INSIGHT study is a noninterventional, prospective, multicenter, observational study performed in 124 sites across Austria and Germany between 2008 and 2014. Median overall survival and time to progression (RECIST) were found to be dependent on baseline Barcelona Clinic Liver Cancer (BCLC) tumor stage (A: 29.2, B: 19.6, C: 13.6, D: 3.1 and A: 6.0, B: 5.5, C: 3.9, and D: 1.7 months, respectively), Child-Pugh liver function (A: 17.6, B: 8.1, C: 5.6 and A: 5.3, B: 3.3, C: 2.5 months, respectively), and performance status of the patient; however, age did not affect prognosis. Sorafenib-related adverse events at any grade occurred in 64.9% of patients, with diarrhea (35.4%), hand-foot-skin reaction (16.6%), nausea (10.3%), and fatigue (11.2%) occurring most frequently. Sorafenib treatment was shown to be effective in a real-life setting, in agreement with previously reported clinical trial data. The therapy was found to have an acceptable safety profile, with predominantly mild to moderate side effects. .

PurposeAlthough treatment for early breast cancer improved prognosis greatly, it can have significant long-term consequences, which must be considered during treatment decision.Methods453 patients with neoadjuvant or adjuvant treatment intention were recruited into the MaTox project within the prospective, multicentre, population-based German TMK cohort study (Tumour Registry Breast Cancer) between 2008 and 2009. Patient-reported outcomes (PROs) on 26 treatment-related symptoms were assessed via a specifically designed questionnaire at 4 weeks, 6 months, 18 months and 3 years after start of systemic treatment.ResultsThe results show that alterations in smell, taste and appetite were clearly improved 3 years after treatment. In contrast, post-surgical symptoms, restrictions in memory/attention, musculoskeletal system and polyneuropathy worsened substantially over time and were persistent after 3 years: 78% of the patients recorded impairment in memory, 73% muscle pain, 67% pain at the operated site and 57% paraesthesia in fingers or toes. A logistic regression model showed that risk factors for developing persistent paraesthesia symptoms were age, early paraesthesia symptoms and taxane-based therapy.ConclusionsOur data show that most patients with breast cancer have persistent impairments negatively influencing their daily life even 3 years after treatment. Furthermore, we highlight areas requiring special attention in follow-up care.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-017-4365-7) contains supplementary material, which is available to authorized users.

BackgroundWe conducted an open-label, randomized, two-arm multi-center study to assess the efficacy and safety of paclitaxel versus paclitaxel + sorafenib in patients with locally advanced or metastatic HER2-negative breast cancer.MethodsPatients were randomly assigned to receive either paclitaxel monotherapy (80 mg/m2) weekly (3 weeks on, 1 week off) plus sorafenib 400 mg orally, twice a day taken continuously throughout 28 day cycles. Sorafenib dose was gradually escalated from a starting dose of 200 mg twice a day. The primary endpoint was progression free survival (PFS).ResultsA pre-planned efficacy interim analysis was performed on the data of 60 patients, 30 patients in each treatment arm. Median PFS was estimated at 6.6 months (95% CI: 5.1 to 9.0) in patients randomized to single-agent paclitaxel (Arm A) and 5.6 months (95% CI: 3.8 to 6.5) in patients randomized to paclitaxel-sorafenib combination (Arm B) therapy. Contrary to the hypothesis, the treatment effect was statistically significant in favor of paclitaxel monotherapy (hazard ratio 1.80, 95% CI: 1.02 to 3.20; log-rank test P = 0.0409). It was decided to stop the trial early for futility. Median OS was also in favor of Arm A (20.7 months (95% CI: 16.4 to 26.7) versus 12.1 months (95% CI: 5.8 to 20.4) in Arm B. Clinical control was achieved in 28 patients (93.3%) in Arm A and in 21 patients 70.0% in Arm B. Overall response rate was met in 43.3% of patients in Arm A and in 40.0% in Arm B. Toxicities were increased in Arm B with higher rates of diarrhea, nausea, neutropenia, hand-foot skin reaction (HFSR) and anorexia, Grad 3 and 4 toxicities were rare.ConclusionsIn this pre-planned interim analysis, paclitaxel-sorafenib combination therapy was not found to be superior to paclitaxel monotherapy with regard to the primary end point, progression-free survival. The trial was therefore discontinued early. There was no indication of more favorable outcomes for combination therapy in secondary efficacy end points. As expected, the safety and toxicity profile of the combination therapy was less favorable compared to monotherapy. Overall, this trial did not demonstrate that adding sorafenib to second- or third-line paclitaxel provides any clinical benefit to patients with HER2-negative advanced or metastatic breast cancer. Cautious dosing using a sorafenib ramp up schedule might have contributed to negative results.Trial registrationThe study was registered at EudraCT (No 2009–018025-73) and retrospectively registered at Clinical trials.gov on March 17, 2011 (NCT01320111).

To our knowledge, our population of elderly patients treated with adjuvant trastuzumab is the largest analyzed so far. The beneficial long-term results were comparable to those in the younger cohorts. Although the risk of cardiotoxicity increased significantly with age, it also remained manageable in older patients. Thus, chronological age alone should not preclude HER2 antibody treatment.

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