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Multicenter Study
. 2020 Jan 1;126(1):98-104.
doi: 10.1002/cncr.32508. Epub 2019 Sep 19.

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

Anna Maria Frezza  1 , Tarek Assi  2 , Salvatore Lo Vullo  3 , Eytan Ben-Ami  4 , Armelle Dufresne  5 , Kan Yonemori  6 , Emi Noguchi  6 , Brittany Siontis  7 , Richard Ferraro  8 , Pawel Teterycz  9 , Florence Duffaud  10 , Vinod Ravi  11 , Bruno Vincenzi  12 , Hans Gelderblom  13 , Maria A Pantaleo  14 , Giacomo G Baldi  15 , Ingrid Desar  16 , Alexander Fedenko  17 , Robert G Maki  18 , Robin L Jones  19 , Robert S Benjamin  11 , Jean Yves Blay  5 , Akira Kawai  6 , Mrinal Gounder  8 , Alessandro Gronchi  20 , Axel Le Cesne  2 , Olivier Mir  2 , Anna M Czarnecka  9 , Scott Schuetze  7 , Andrew J Wagner  4 , Julien Adam  21 , Marta Barisella  22 , Marta Sbaraglia  23 , Jason L Hornick  24 , Alexandra Meurgey  25 , Luigi Mariani  3 , Paolo G Casali  1   26 , Katherine Thornton  4 , Silvia Stacchiotti  1
Affiliations
Multicenter Study

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

Anna Maria Frezza et al. Cancer. .

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.

Keywords: MDM2; anthracycline; gemcitabine; intimal sarcoma; pazopanib; systemic therapies.

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Conflict of interest statement

Conflict of interest statement

AMF received institutional clinical trials support from Amgen Dompé, AROG Bayer, Blueprint Medicines, Eli Lilly, Daiichi Sankyo Pharma, Epizyme, GlaxoSmithKline, Novartis, Pfizer, PharmaMar and travel grants from PharmaMar.

BV received consultancy and advisory honoraria from Bayer, Eisai, Eli Lilly, Novartis, Pfizer, PharmaMar, Abbott; honoraria from Novartis, Pfizer, PharmaMar, Abbott; institutional research funding from Eli Lilly, Novartis and PharmaMar.

GGB received travel grants and advisory honoraria from Pharmamar and Eli Lilly, advisory honoraria from Eisai.

RGM received consulting fees and institutional clinical trials support from Lilly, Novartis, Roche and Glaxo Smith Kline.

JYB received research support and honoraria from Novartis, Bayer, GSK, Pharmamar.

AG received advisory honoraria from Deciphera Pharmaceuticals, Eisai, Eli Lilly, Nectar Therapeutics; speaker’s honoraria from Eisai, Eli Lilly, Pfizer, PharmaMar; research support from Amgen Dompé, AROG Bayer, Blueprint Medicines, Eli Lilly, Daiichi Sankyo Pharma, Epizyme, GlaxoSmithKline, Novartis, Pfizer, PharmaMar.

ALC received honoraria from Pharmamar, Lilly, Amgen, Pfizer.

OM received consultancy honoraria from Amgen, Astra-Zeneca, Bayer, Blueprint Medicines, Bristol Myers-Squibb, Eli-Lilly, Incyte, Ipsen, Lundbeck, MSD, Novartis, Pfizer, Roche, Servier, Vifor Pharma; board membership from Amgen, Astra-Zeneca, Bayer, Blueprint Medicines, Bristol Myers-Squibb, Eli-Lilly, Lundbeck, MSD, Novartis, Pfizer, Roche, Servier, Vifor Pharma; speakers bureau from Eli-Lilly, Roche, Servier; stock ownership for Amplitude surgical, Transgene.

SS received research support from Adaptimmune, Amgen, Glaxo Smith Kline, Karyopharm, Lilly; honorarium from NanoCarrier.

JH received consultancy honoraria from Eli Lilly and Epizyme.

AJW has reported consulting roles for Daiichi-Sankyo, Eli Lilly, Five Prime Therapeutics, Nanosphere; received honoraria from Novartis and institutional research support from Daiichi-Sankyo, Plexxikon, Eli Lilly, Aadi Bioscience, Five Prime Therapeutics, Karyopharm

PGC has reported advisory roles for Deciphera Pharmaceuticals, Eisai, Eli Lilly, Nektar Therapeutics, speaker’s honoraria from Eisai, Eli Lilly, Pfizer, PharmaMar, and conducted studies sponsored by Amgen Dompé, AROG Bayer, Blueprint Medicines, Eli Lilly, Daiichi Sankyo Pharma, Epizyme, GlaxoSmithKline, Novartis, Pfizer, PharmaMar.

KT hase served on an advisory board for Agios.

SSt has received honoraria from Eli Lilly, PharmaMar, Takeda; institutional research grants from Amgen Dompé, Advenchen, Bayer, Eli Lilly, Daiichi Sankyo Pharma, Epizyme Inc., Novartis, Pfizer and PharmaMar; travel grants from PharmaMar and has reported advisory/consultant roles for Bayer, Daiichi, Eli Lilly, Epizyme, Karyopharm, ImmuneDesign, Maxivax and PharmaMar

TA, SLV, EBA, AD, KY, EN, BS, PT, FD, VR, HG, MP, ID, AF, RLJ, RGB, AK, JA, MB, AMC, MS, AM, LM have nothing to disclose.

Figures

Figure 1.
Figure 1.. Intimal sarcoma patients treated with anthracycline-based regimens.
Kaplan-Meier curves for recurrence-free survival (A) and overall survival (B) in patients treated for localized disease with curative intent (n=24); progression-free survival (C) and overall survival (D) in patients treated for advanced disease with palliative intent (n=42).
Figure 1.
Figure 1.. Intimal sarcoma patients treated with anthracycline-based regimens.
Kaplan-Meier curves for recurrence-free survival (A) and overall survival (B) in patients treated for localized disease with curative intent (n=24); progression-free survival (C) and overall survival (D) in patients treated for advanced disease with palliative intent (n=42).
Figure 1.
Figure 1.. Intimal sarcoma patients treated with anthracycline-based regimens.
Kaplan-Meier curves for recurrence-free survival (A) and overall survival (B) in patients treated for localized disease with curative intent (n=24); progression-free survival (C) and overall survival (D) in patients treated for advanced disease with palliative intent (n=42).
Figure 1.
Figure 1.. Intimal sarcoma patients treated with anthracycline-based regimens.
Kaplan-Meier curves for recurrence-free survival (A) and overall survival (B) in patients treated for localized disease with curative intent (n=24); progression-free survival (C) and overall survival (D) in patients treated for advanced disease with palliative intent (n=42).
See this image and copyright information in PMC

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