Treatment of platinum refractory or resistant ovarian cancer

In The Lancet Oncology, Radoslav Chekerov and colleagues 1 report the results of a randomised phase 2 trial of the efficacy and safety of adding sorafenib (an oral tyrosine kinase inhibitor of the VEGF receptor and Ras, Raf, MEK, and ERK signalling pathways) to topotecan during chemotherapy and in maintenance in recurrent platinum-resistant or platinum-refractory ovarian cancer. 1 The investigators faced a clinically relevant issue for medical and gynaecological oncologists; for decades, this patient setting has represented a disappointing challenge considering the low proportion of patients who achieve a response to conventional cytotoxic drugs, and short duration of time to progression, even with the use of doublets, which led only to worsening of toxicity. The recent acknowledgment of the role of the microenvironment in tumour progression has resulted in the identification of several molecular targets and pathways driving tumour-associated angiogenesis, invasiveness, metastatic potential, host immunosuppression, and acquired chemoresistance. 2 , 3 Although the identification of tumour angiogenic factors dates back to the 1970s, clinical development of an antiangiogenic drug for management of ovarian cancer only started 10 years ago, and led to the introduction of bevacizumab among the therapeutic options in first-line and salvage treatment of platinum-sensitive and platinum-resistant relapse of disease. 4 The increased interest in the tumour microenvironment has also accelerated the development of pleiotropic tyrosine kinase inhibitors that are able to block pathways driven by angiogenic and growth stimulating factors. Among these, sorafenib has been investigated previously in patients with ovarian cancer, but provided only modest results. 5