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In patients with advanced gastric cancer with high expression of HER2 protein, the addition of trastuzumab to chemotherapy significantly improves overall survival compared with chemotherapy alone in the first line setting. However, there are no data on anti-HER2 therapies beyond disease progression after first-line therapy. In many types of cancers, including gastric cancer, dysregulation of the receptor tyrosine kinase MET may lead to a more aggressive cancer phenotype and may be a negative prognostic indicator. Therapeutic targeting of MET/hepatocyte growth factor (HGF) signalling has used monoclonal antibodies and smallmolecule tyrosine kinase inhibitors (TKIs) against the MET receptor and its ligand, with several drugs in latephase clinical trials, including onartuzumab. Onartuzumab is a humanized monovalent monoclonal antibody directed against the hepatocyte growth factor receptor (c-Met). In advanced gastric cancer, the addition of onartuzumab to a standard chemotherapy regimen with oxaliplatin and fluoropyrimidine did not improve efficacy in gastric cancer patients in the overall study population or in those selected for positive MET status by immunohistochemistry. In this clinical case we observed a good clinical response to FOLFOX plus onartuzumab in a young patient with MET-positive gastric cancer. However, therapy with cisplatin, 5-fluorouracil and trastuzumab used after progression did not provide a benefit. This case report therefore highlights the importance of always fully identifying potential therapeutic targets in our patients in order to offer more personalized therapies. A correct molecular analysis is very important in deciding the therapeutic sequences in the metastatic setting.

Background Pazopanib is a multikinase inhibitor registered for the treatment of advanced renal clear cell carcinoma (RCC) and as second or further-line therapy in advanced non-adipocytic soft tissue sarcoma (STS). It is a relatively well-tolerated compound, but, as with many other tyrosine kinase inhibitors (TKI), chronic toxicity may become a challenge that both patient and physician need to take into account when starting treatment. This retrospective study investigated toxicities and their management in STS patients treated with pazopanib in routine clinical practice in Italy. Materials and Methods Data were collected between January 2013 and May 2016 at Candiolo Cancer Institute and Prato Medical Oncology Unit. The primary objective was to describe observed toxicities in a real-life setting, and use this information to inform strategies for adverse event management. Results A total of 43 patients with advanced STS who received treatment with pazopanib were included. Median progression-free survival was 4 months and median overall survival was 18 months. The most common toxicities were fatigue (74.4%), hypertension (72%), hair hypopigmentation (74.4%) and diarrhea (60.5%). Liver toxicities occurred in less than one-third of patients. Severe adverse events, requiring drug interruption, were relatively rare. Conclusions This study confirms the safety and efficacy of pazopanib in pretreated unresectable or metastatic soft tissue sarcoma, and highlights the importance of close follow-up and patient support to improve compliance and treatment duration.

Leiomyosarcomas (LMS) represent a large subgroup of soft-tissue sarcoma (STS) generally considered moderately sensitive to conventional chemotherapy. Single-agent doxorubicin is the standard first-line therapy for advanced non-selected STS, although combination with ifosfamide appears to be superior in terms of objective response. Gemcitabine-based regimes, dacarbazine, trabectedin and pazopanib seem to be especially active in patients with advanced LMS, while the activity of ifosfamide in this histotype is low. Data derived from clinical trials and retrospective series show that trabectedin is especially active in L-sarcomas including non-gynecological and uterine LMS as well as liposarcomas, in particular myxoid liposarcomas. Trabectedin has also been tested in the first-line setting, alone or in combination with doxorubicin, for the treatment of LMS of uterine and non-uterine origin in a trial by the French Sarcoma Group (phase II study LMS-02) with encouraging results in terms of median progression-free survival and objective response. The toxicity profile of trabectedin appears to be comparable to, or even more manageable than, that of other chemotherapy combinations in the first-line setting. Designing new clinical trials based on specific histologic subtypes is feasible, and the results of such studies would help to optimize the management of patients with STS.