Crizotinib therapy for advanced lung adenocarcinoma and a ROS1 rearrangement: results from the EUROS1 cohort.

PURPOSE: Approximately 1% of lung adenocarcinomas are driven by oncogenic ROS1 rearrangement. Crizotinib is a potent inhibitor of both ROS1 and ALK kinase domains. PATIENTS AND METHODS: In the absence of a prospective clinical trial in Europe, we conducted a retrospective study in centers that tested for ROS1 rearrangement. Eligible patients had stage IV lung adenocarcinoma, had ROS1 rearrangement according to fluorescent in situ hybridization, and had received crizotinib therapy through an individual off-label use. Best response was assessed locally using RECIST (version 1.1). All other data were analyzed centrally. RESULTS: We identified 32 eligible patients. One patient was excluded because next-generation sequencing was negative for ROS1 fusion. Median age was 50.5 years, 64.5% of patients were women, and 67.7% were never-smokers. Thirty patients were evaluable for progression-free survival (PFS), and 29 patients were evaluable for best response. We observed four patients with disease progression, two patients with stable disease, and objective response in 24 patients, including five complete responses (overall response rate, 80%; disease control rate, 86.7%). Median PFS was 9.1 months, and the PFS rate at 12 months was 44%. No unexpected adverse effects were observed. Twenty-six patients received pemetrexed (either alone or in combination with platinum and either before or after crizotinib) and had a response rate of 57.7% and a median PFS of 7.2 months. CONCLUSION: Crizotinib was highly active at treating lung cancer in patients with a ROS1 rearrangement, suggesting that patients with lung adenocarcinomas should be tested for ROS1. Prospective clinical trials with crizotinib and other ROS1 inhibitors are ongoing or planned.

Radiation recall dermatitis with soft tissue necrosis following pemetrexed therapy: a case report.

INTRODUCTION: Radiation recall dermatitis is a well known but still poorly understood inflammatory reaction. It can develop in previously irradiated areas and has been shown to be triggered by a variety of different drugs, including cytostatic agents. Pemetrexed may cause radiation recall dermatitis in pre-irradiated patients. CASE PRESENTATION: We present the case of a 49-year-old Caucasian woman with non-small cell lung cancer who was initially treated with carboplatin and paclitaxel concomitant with radiotherapy after suffering a painful plexus brachialis infiltration. Due to disease progression, a second-line treatment with pemetrexed was started. A severe soft tissue necrosis developed despite steroid treatment and plastic surgery. CONCLUSION: To the best of our knowledge, we present the first case of a patient with severe soft tissue necrosis in a pre-irradiated area after pemetrexed therapy. We believe that physicians treating patients with pemetrexed should be aware of the severe, possibly life-threatening effects that may be induced by pemetrexed after previous radiation therapy.

[New treatment approaches in breast cancer]. / Neue Behandlungsansätze beim Mammakarzinom.

A great step was taken in the treatment of the prognostically unfavourable group of Her2-positive breast cancer in the past years with the introduction of the targeted therapy with trastuzumab, which showed significant increase in median survival in the metastatic and adjuvant setting of Her2-positive breast cancer patients. Lapatinib, an oral HER2-tyrosine kinase inhibitor, showed activity in patients with breast cancer progression after trastuzumab. The role of lapatinib in the adjuvant setting will be examined in the ongoing, multicenter, prospective, four-arm ALTTO-trial, which compares the current standard treatment of one year trastuzumab against lapatinib, the combination of trastuzumab and lapatinib and an arm with sequential trastuzumab followed by lapatinib. Another promising treatment option is the VEGF-antibody bevacizumab, which blocks tumor-mediated angiogenesis leading to oxygen undersupply and finally growth inhibition of the tumor. Concerning treatment decision, two ongoing prospective trials in the USA and Europe are eagerly awaited, which examine the role of gene-array assessment in terms of risk stratification and finally tailoring adequate treatment.