Systemic treatments in MDM2 positive intimal sarcoma: A multicentre experience with anthracycline, gemcitabine, and pazopanib within the World Sarcoma Network

Abstract

Background Intimal sarcoma (InS) is an exceedingly rare neoplasm with an unfavorable prognosis, for which new potentially active treatments are under development. We report on the activity of anthracycline‐based regimens, gemcitabine‐based regimens, and pazopanib in patients with InS. Methods Seventeen sarcoma reference centers in Europe, the United States, and Japan contributed data to this retrospective analysis. Patients with MDM2‐positive InS who were treated with anthracycline‐based regimens, gemcitabine‐based regimens, or pazopanib between October 2001 and January 2018 were selected. Local pathological review was performed to confirm diagnosis. Response was assessed by RECIST1.1. Recurrence‐free survival (RFS), progression‐free survival (PFS) and overall survival were computed by Kaplan‐Meier method. Results Seventy‐two patients were included (66 anthracycline‐based regimens; 26 gemcitabine‐based regimens; 12 pazopanib). In the anthracycline‐based group, 24 (36%) patients were treated for localized disease, and 42 (64%) patients were treated for advanced disease. The real‐world overall response rate (rwORR) was 38%. For patients with localized disease, the median RFS was 14.6 months. For patients with advanced disease, the median PFS was 7.7 months. No anthracycline‐related cardiac toxicity was reported in patients with cardiac InS (n = 26). For gemcitabine and pazopanib, the rwORR was 8%, and the median PFS was 3.2 and 3.7 months, respectively. Conclusion This retrospective series shows the activity of anthracycline‐based regimens in InS. Of note, anthracyclines were used in patients with cardiac InS with no significant cardiac toxicity. The prognosis in patients with InS remains poor, and new active drugs and treatment strategies are needed.

Nationwide incidence of sarcomas and connective tissue tumors of intermediate malignancy over four years using an expert pathology review network

“…This requires a coordinated effort, worldwide, to achieve this goal given the rarity of certain histotypes. This is currently being conducted by intergroup studies, and international networks such as WSN or more recently EURACAN [26][27][28]. This work also confirms the importance of national registries to investigate these rare subtypes.…”

“…Overall, this calls for a revision of the criteria to define standard treatment for such rare tumors where phase III are hardly or not feasible [26][27][28][29]. Health authorities and reimbursement bodies should adapt their decisions on approval and reimbursement on the feasible level of evidence which could be reached for tumors with and incidence <1/10 6 per year in order not to discriminate against patients with rare cancers.…”

Primary Soft Tissue Sarcoma of the Heart: An Emerging Chapter in Cardio-Oncology

“…The anthracycline group did not present any cardiac toxicity event, with a real-world overall response rate (rwORR) equal to 38% [83]. Gemcitabine was mostly adopted as a second-line treatment (77% of cases), demonstrating rwORR equal to 8% [83]. The same results (rwORR = 8%) occurred for pazopanib-a tyrosine kinase inhibitor (TKI) with anti-angiogenetic properties-which was considered as a further line therapy in advanced diseases [83].…”

“…Although further chemotherapeutic agents might theoretically be applied in pSTS-h, no randomized controlled trial/studies have been performed, and thus no definite indications may be provided. Frezza et al [83] retrospectively evaluated the efficacy and safety of chemotherapies (i.e., anthracycline, gemcitabine, pazopanib) in 72 patients with intimal sarcoma. The anthracycline group did not present any cardiac toxicity event, with a real-world overall response rate (rwORR) equal to 38% [83].…”

“…Frezza et al [83] retrospectively evaluated the efficacy and safety of chemotherapies (i.e., anthracycline, gemcitabine, pazopanib) in 72 patients with intimal sarcoma. The anthracycline group did not present any cardiac toxicity event, with a real-world overall response rate (rwORR) equal to 38% [83]. Gemcitabine was mostly adopted as a second-line treatment (77% of cases), demonstrating rwORR equal to 8% [83].…”