For reprint orders, please contact:
[email protected]
Future Oncology
Editorial
New drugs and clinical trial design in advanced sarcoma: have we made any progress? “The important question … is whether the lack of survival benefit associated with systemic therapy could be a reflection, at least partly, of the way clinical trials have been conducted in these heterogeneous diseases.” Anastasia Constantinidou1, Aisha Miah1, Seth Pollack2 & Robin L Jones*2 The Royal Marsden Hospital & the Institute of Cancer Research, London, UK University of Washington/Fred Hutchinson Cancer Research Center, Seattle, WA, USA *Author for correspondence: Tel.: +1 206 288 7439 n Fax: +1 206 288 6618 n
[email protected] 1 2
Doxorubicin alone or in combination with ifosfamide has been the dominant systemic therapy regimen in the management of advanced/metastatic soft tissue sarcoma (STS) for several decades. Recently, other chemo therapy drugs have emerged as effective options in specific histological subtypes, including the combination of gemcitabine and docetaxel in uterine leiomyosarcoma [1], trabectedin in leio myosarcoma and liposarcoma [2], and paclitaxel in angiosarcoma [3]. In addition, the efficacy of several tyrosine kinase inhibitors in gastro intestinal stromal tumors (GIST) and in other rare, specific histological subtypes clearly high lights the importance of using different systemic therapy options for these different diseases. Despite these advances, evidence to support pro longation of survival in patients with advanced STS treated with systemic therapy remains limited. The important question arising here is whether the lack of survival benefit associated with systemic therapy could be a reflection, at least partly, of the way clinical trials have been conducted in these heterogeneous diseases. A number of problems have been raised over the years in relation to the design and execu tion of clinical trials in STS. One interesting example is that of a large randomized Phase III trial comparing the VEGFR inhibitor pazopanib with placebo in patients previously treated with chemotherapy (PALETTE) [4]. This showed a significantly longer median progression-free survival (PFS) for patients treated with pazo panib compared with placebo: 4.6 months (95% CI: 3.7–4.8) for pazopanib compared with 1.6 months (95% CI: 0.9–1.8) for placebo (hazard ratio [HR]: 0.31; 95% CI: 0.24–0.40; p
