Efficacy of second and third lines of treatment in advanced soft tissue sarcomas: a real-world study

Background Soft tissue sarcomas (STSs) are an uncommon and heterogeneous group of tumours. Several drugs and combinations have been used in clinical practice as second-line (2L) and third-line (3L) treatment. The growth modulation index (GMI) has previously been used as an exploratory efficacy endpoint of drug activity and represents an intra-patient comparison. Methods We performed a real-world retrospective study including all patients with advanced STS who had received at least 2 different lines of treatment for advanced disease between 2010 and 2020 at a single institution. The objective was to study the efficacy of both 2L and 3L treatments, analysing the time to progression (TTP) and the GMI (defined as the ratio of TTP between 2 consecutive lines of therapy). Results Eighty-one patients were included. The median TTP after 2L and 3L treatment was 3.16 and 3.06 months, and the median GMI was 0.81 and 0.74, respectively. The regimens most frequently used in both treatments were trabectedin, gemcitabine-dacarbazine, gemcitabine-docetaxel, pazopanib and ifosfamide. The median TTP by each of these regimens was 2.80, 2.23, 2.83, 4.10, and 5.00 months, and the median GMI was 0.78, 0.73, 0.67, 1.08, and 0.94, respectively. In terms of histotype, we highlight the activity (GMI > 1.33) of gemcitabine-dacarbazine in undifferentiated pleomorphic sarcoma (UPS) and in leiomyosarcoma, pazopanib in UPS, and ifosfamide in synovial sarcoma. Conclusions In our cohort, regimens commonly used after first-line STS treatment showed only slight differences in efficacy, although we found significant activity of specific regimens by histotype (AU)

Efficacy of second and third lines of treatment in advanced soft tissue sarcomas: a real-world study.

BACKGROUND: Soft tissue sarcomas (STSs) are an uncommon and heterogeneous group of tumours. Several drugs and combinations have been used in clinical practice as second-line (2L) and third-line (3L) treatment. The growth modulation index (GMI) has previously been used as an exploratory efficacy endpoint of drug activity and represents an intra-patient comparison. METHODS: We performed a real-world retrospective study including all patients with advanced STS who had received at least 2 different lines of treatment for advanced disease between 2010 and 2020 at a single institution. The objective was to study the efficacy of both 2L and 3L treatments, analysing the time to progression (TTP) and the GMI (defined as the ratio of TTP between 2 consecutive lines of therapy). RESULTS: Eighty-one patients were included. The median TTP after 2L and 3L treatment was 3.16 and 3.06 months, and the median GMI was 0.81 and 0.74, respectively. The regimens most frequently used in both treatments were trabectedin, gemcitabine-dacarbazine, gemcitabine-docetaxel, pazopanib and ifosfamide. The median TTP by each of these regimens was 2.80, 2.23, 2.83, 4.10, and 5.00 months, and the median GMI was 0.78, 0.73, 0.67, 1.08, and 0.94, respectively. In terms of histotype, we highlight the activity (GMI > 1.33) of gemcitabine-dacarbazine in undifferentiated pleomorphic sarcoma (UPS) and in leiomyosarcoma, pazopanib in UPS, and ifosfamide in synovial sarcoma. CONCLUSIONS: In our cohort, regimens commonly used after first-line STS treatment showed only slight differences in efficacy, although we found significant activity of specific regimens by histotype.

Comparison of 2-Weekly and 3-Weekly Dosing of Docetaxel in Metastatic Prostate Cancer.

INTRODUCTION: Docetaxel 75 mg/m2 every 3 weeks is the standard schedule for metastatic prostate cancer (mPC). Alternative dosing of 50 mg/m2 every 2 weeks may be an option for frail patients. Our aim is to define which factors influence the choice of schedule and to compare the outcomes of both schedules in daily clinical practice. PATIENTS AND METHODS: We retrospectively included patients with mPC treated with docetaxel in our institution. We compared data from patients treated with 3-weekly, 75 mg/m2 docetaxel or 2-weekly, 50 mg/m2 docetaxel, including basal characteristics, predefined prognostic factors, treatment received, toxicity and survival data. RESULTS: We included 200 patients, 86% of whom presented castration resistant mPC. A total of 158 patients (79%) were treated with 3-weekly scheme. Compared with these patients, patients treated with 2-weekly scheme were significantly older, had higher Eastern Cooperative Oncology Group performance status (ECOG PS) and Charlson Comorbidity Index, presented more visceral metastases and needed opioid treatment more frequently. Patients treated with 2-weekly scheme presented shorter median overall survival; however, these differences were not shown after multivariate analysis with significant prognostic factors. Patients treated with 2-weekly scheme had more treatment delays and suspensions, but less clinically impairing toxicities such as febrile neutropenia, neuropathy and diarrhea; toxic deaths were 5 in the 3-weekly group while none in the 2-weekly group. CONCLUSION: Compared to docetaxel 75 mg/m2 every 3 weeks, dosing of 50 mg/m2 every 2 weeks may be an alternative for older, frailer and more comorbid patients. Two-weekly dosing may be used more frequently in selected patients.