The choice of second-line therapy for patients with advanced soft tissue sarcomas

Systemic treatment of patients with advanced STS may include cytotoxic chemotherapy and/or targeted therapy. Although the use of targeted drugs with a more favorable toxicity profile than cytotoxic drugs is more attractive, the use of cytotoxic therapy generally demonstrates better results. Currently, different morphological types of soft tissue sarcomas require different therapies. Necessity of carrying out of 2^nd and more lines of therapy at SMT does not raise doubts, however now clear algorithms of treatment are not yet developed.
Objective. To evaluate the efficacy of trabectedin, pazopanib and a combination of gemcitabine and docetaxel as a second line of treatment for patients with soft tissue sarcomas
Materials and methods. 106 patients with different STS were divided into three treatment groups: 1st group of patients (n=43) received trabectedin 1,5 mg/m2 as a 24-hour continuous intravenous infusion every 3 weeks; The 2nd group of patients (n=37) received pazopanib 800 mg orally once a day; third group of patients (n=26) received combination of gemcitabine and docetaxel (GemTax): gemcitabine 900 mg/m2 IV in a 1,5 hour infusion on days 1 and 8, docetaxel 100 mg/m2 IV the 8th day every 3 weeks with G-CSF support. Tumor assessment was done according to RECIST 1.1 criteria.
Results. The efficacy of the combination of gemcitabine and docetaxel was evaluated in 26 patients: CR – 1 patient (3,8%), PR – 6 patients (23,1%), SD – 13 patients (50%), PD – 6 patients (23,1%). Thus, tumor control rate (complete remission, partial remission, stabilization) was 76,9%. The median time to progression was 6,7 months. The median overall survival was 15,4 months.
The effectiveness of pazopanib was evaluated in 37 patients: CR – 0%, PR – 4 patients (10,8%), SD – 27 patients (73%), PD – 6 patients (16,2%). Thus, tumor control rate was 83,8%. The median time to progression was 7 months. Median overall survival was 14,5 months.
Efficacy of trabectedin was evaluated in 43 patients: CR – 0%, PR – 4 patients (9,3%), SD – 21 patients (48,8%), PD – 18 patients (41,9%). Thus, tumor control rate was 58,1%. The median time to progression was 2,3 months. Median overall survival was 10,3 months. The toxicity profile did not differ from the world published data.
Conclusions. When comparing chemotherapy regimens, we obtained the following data – for leiomyosarcomas and angiosarcomas, the use of high-dosage chemotherapy GemTax as the second line showed the highest indices of median PFS 10 and 8,2 months, respectively. The median OS was 14,7 and 15,3 months, respectively. For synovial sarcomas, the use of pazopanib showed the longest median PFS equal to 14 months. Median OS was 15,5 months, so pazopanib the most preferable regimen of second line therapy. In case of liposarcomas, the use of trabectedin in the second line shows the best results: the median PFS was 2,1 months, and the median OS was 8,3 months. With insensitive and weakly sensitive subtypes of soft tissue sarcomas to standard chemotherapy regimens, pazopanib shows high rates of median PFS and OS. Therefore, the use of pazopanib is possible both in the second line of therapy, and also in the front line of treatment for chemoresistant subtypes of advanced STS.

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