Optimizing Systemic Therapy for Advanced Sarcomas: Outcomes With Gemcitabine, Docetaxel, Cisplatin, and Everolimus in...

Advanced sarcomas have limited treatment options. Gemcitabine and docetaxel (GD) regimen showed efficacy in soft tissue sarcomas (STSs) in phase II studies but failed in first-line phase III trial. Adding cisplatin to GD showed efficacy in other types of cancer. mTOR pathway has been shown to play a role in resistance to these drugs. Inflammatory biomarkers have been identified as potential prognostic indicators in various malignancies, but their role in patients with advanced sarcomas is not clear.

We retrospectively enrolled 77 patients with advanced or metastatic sarcomas (STSs, n = 71; bone sarcomas, n = 6) receiving a novel combination with gemcitabine-gemcitabine/docetaxel/cisplatin plus everolimus (G-GDC + E). Primary endpoints included overall survival (OS) and progression-free survival (PFS). Inflammatory biomarkers were calculated, and their prognostic influence was evaluated.

The median OS and PFS were 16.8 months (95% CI, 13.6-23.9) and 5.4 months (95% CI, 4.3-8.3), respectively. Undifferentiated pleomorphic sarcoma/myxofibrosarcoma (UPS/MFS) demonstrated superior PFS compared to round cell sarcoma/translocation-related sarcoma (7.8 vs. 3.6 months, p = 0.009) and bone sarcoma (7.8 vs. 2.3 months, p < 0.001). Eastern Cooperative Oncology Group Performance Status ≥ 2, unfavorable histology (round cell sarcoma/translocation-related sarcoma and bone sarcoma), lower albumin level, and lymphocyte-to-monocyte ratio < 2.7 were independent predictors of OS. Grade 3-4 toxicities included neutropenia (68.8%), thrombocytopenia (59.7%), anemia (49.4%), diarrhea (18.2%), and skin toxicities (28.6%).

G-GDC + E demonstrates histology-specific efficacy in advanced/metastatic sarcomas, with substantial hematologic toxicity (Grade 3-4 thrombocytopenia 59.7%, neutropenia 68.8%) and notable non-hematologic events (Grade 3-4 diarrhea 18.2%, skin reactions 28.6%), all controllable with close monitoring, dose modifications and supportive care. Inflammatory biomarkers provide independent prognostic values.