Leiomyosarcoma of the stomach is an extremely rare malignancy for which treatment in advanced disease is hardly reported. Here, we report a case of a 48-year-old man with metastatic gastric Leiomyosarcoma who had previously received a combination of gemcitabine and docetaxel followed by pazopanib after detection of metastasis. The patient was started on trabectedin as per protocol and had disease control continuing for 17 cycles of trabectedin. His quality of life and absence of significant toxicities highlight the noncumulative nature of trabectedin and potential benefit in responding cases.
Background: In this decade the treatment of advanced sarcoma has seen many highs and lows in terms of successful trials and failed trials. This is possible due to great collaborations, newer therapies and histology focused trials. Methods: In ASCO 2019 many sarcoma trials were presented and we chose 3 challenging clinical trials that widen our perspective on soft tissue sarcoma. We have critically analyzed the data and have discussed the implications of these trials on current practice. First trial was ANNOUNCE trial which was done to confirm the efficacy of olaratumab after its dramatic success in advanced soft tissue sarcoma in a phase 2 trial. Another trial STRASS trial, which was unique because of being first successfully conducted randomized trial addressing preoperative radiotherapy in retroperitoneal soft tissue sarcoma. Third trial was phase 2 trial SARC 028 trial exploring the role of immunotherapy in pleomorphic undifferentiated sarcoma and liposarcoma subgroup. Result: ANNOUNCE trial failed to show OS benefit in olaratumab/doxorubicin arm as compared to doxorubicin/placebo arm . Based upon this FDA has revoked the approval of olaratumab leading to nihilism and disappointment amongst oncologists. In STRASS trial failed to meet the primary end point though there was a benefit in the liposarcoma subgroup in terms of abdominal recurrence free survival. There are several reasons that this trial might have failed. First, RPSs are not homogeneous population. RPSs might behave very differently as per the histopathology ranging from well differentiated LPS to leiomyosarcoma. Since the event rate in well-differentiated liposarcoma might happen late, the median follow-up of 43 months might not be sufficient. In SARC trial ORR in pleomorphic undifferentiated sarcoma (PUS) cohort was 9/40 (22.5%), while response rates in liposarcoma cohort were 4/39 (10.2%). There was poor correlation between the response and the tumor cells’ PD-L1 positivity. Simultaneously, we must not take for granted the role of pembrolizumab in PUS as the previous study (PEMBROSARC) had also showed dismal outcomes with immunotherapy. Conclusion: In this paper we discuss the intricacies of these trials and how they affect the rapidly changing landscape in advanced soft tissue sarcoma.
No abstract
e22555 Background: The approved dose of pazopanib in advanced STS is 800 mg/day and is not weight based. After initial patients who couldn’t tolerate pazopanib we started pazopanib at lower doses escalating to higher doses. There is already preliminary data about low dose pazopanib in asian patients. Methods: We retrospectively analysed the prospectively kept data base of patients with advanced non adipocytic STS who were treated with pazopanib at AIIMS sarcoma medical oncology clinic between September 2015 and February 2019. After start of pazopanib we get CT scan done every 3 monthly as institutional protocol. Statistical analysis was done by SPSS 23. Results: There were total of 66 patients with median age 40 yrs (17 – 81)and majority were males who (60). ECOG Performance status (PS) was PS 1 in 63% and PS 2 in 23%. Most common diagnosis was synovial sarcoma (22%), leiomyosarcoma (18 %), angiosarcoma (9%), MPNST(8%) and others (43%). Most of the patients received pazopanib as second line (59%) and third line (31%). 90% of patients received dose of 400 mg and remaining 10% of the patients received 600 mg of dose (in which it could be escalated after 1 month). Median weight was 63kg and median height in our patients was 160cm while the median BSA was 1.6. Dose escalation was attempted, but was not feasible due to toxicities. Out of total 66 patients, 57 were available for response assessment. RECIST responses were complete response (CR) was present in 2.9%, partial response (PR) in 17% , stable disease (SD) in 28%. The median progression free survival (PFS) was 5 months and median overall survival was 18 months after a median duration of follow up of 20 months. Grade 3 and grade 4 toxicities were present in 31% of the patients. Grade 3 hand foot syndrome (HFS) was present in 12% of patients.4.5% had hypertension. Other grade 3 and 4 toxicities were oral mucositis (6%) , transaminitis (4%) Cardiomyopathy (3%) and cholestasis jaundice (1.5%) with bilirubin elevated to the level on 19.1 mg/dl. This resolved after stoppage of Pazopanib. Conclusions: Pazopanib at low doses in our series was as efficacious and with similar toxicity as previous literature The option of lower dose pazopanib needs to be explored in Asian population who have lower body weight.
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