Anthracycline, gemcitabine, and pazopanib in epithelioid sarcoma a multi-institutional case series

Anna Maria Frezza, Robin L. Jones, Salvatore Lo Vullo, Naofumi Asano, Francesca Lucibello, Eytan Ben-Ami, Ravin Ratan, Pawel Teterycz, Kjetil Boye, Mehdi Brahmi, Emanuela Palmerini, Alexander Fedenko, Bruno Vincenzi, Antonella Brunello, Ingrid M.E. Desar, Robert S. Benjamin, Jean Yves Blay, Javier Martin Broto, Paolo G. Casali, Hans Gelderblom & 24 others Giovanni Grignani, Alessandro Gronchi, Kirsten Sundby Hall, Olivier Mir, Piotr Rutkowski, Andrew J. Wagner, Olga Anurova, Paola Collini, Angelo P.Dei Tos, Uta Flucke, Jason L. Hornick, Ingvild Lobmaier, Terrier Philippe, Piero Picci, Dominique Ranchere, Salvatore L. Renne, Marta Sbaraglia, Khin Thway, Michal Wagrodzki, Wei Lien Wang, Akihiko Yoshida, Luigi Mariani, Akira Kawai, Silvia Stacchiotti

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

IMPORTANCE Epithelioid sarcoma (ES) is an exceedingly rare malignant neoplasm with distinctive pathologic, molecular, and clinical features as well as the potential to respond to new targeted drugs. Little is known on the activity of anthracycline-based regimens, gemcitabine-based regimens, and pazopanib in this disease. OBJECTIVE To report on the activity of anthracycline-based regimens, gemcitabine-based regimens, and pazopanib in patients with advanced ES. DESIGN, SETTING, AND PARTICIPANTS Seventeen sarcoma reference centers in Europe, the United States, and Japan contributed data to this retrospective analysis of patients with locally advanced/metastatic ES diagnosed between 1990 and 2016. Local pathological review was performed in all cases to confirm diagnosis according to most recent criteria. EXPOSURES All patients included in the study received anthracycline-based regimens, gemcitabine-based regimens, or pazopanib. MAIN OUTCOME AND MEASURES Responsewas assessed by RECIST. Progression-free survival (PFS) and overall survival (OS) were computed by Kaplan-Meier method. Classic and proximal subtypes were defined based on morphology (according to 2013World Health Organization guidelines). RESULTS Overall, 115 patients were included, 80 (70%) were men and 35 (30%) were women, with a median age of 32 years (range, 15-77 years). Of the 115 patients with ES, 85 were treated with anthracycline-based regimens, 41 with gemcitabine-based regimens, and 18 with pazopanib. Twenty-four received more than 1 treatment. Median follow-up was 34 months. Response rate for anthracycline-based regimens was 22%, with a median PFS of 6 months. One complete response (CR) was reported. A trend toward a higher response rate was noticed in morphological proximal type (26%) vs classic type (19%) and in proximal vs distal primary site (26%vs 18%). The response rate for gemcitabine-based regimens was 27%, with 2 CR and a median PFS of 4 months. In this group, a trend toward a higher response rate was reported in classic vs proximal morphological type (30% vs 22%) and in distal vs proximal primary site (40% vs 14%). In the pazopanib group, no objective responses were seen, and median PFS was 3 months. CONCLUSIONS AND RELEVANCE This is the largest retrospective series of systemic therapy in ES.We confirm a moderate activity of anthracycline-based and gemcitabine-based regimens in ES, with a similar response rate and PFS in both groups. The value of pazopanib was low. These data may serve as a benchmark for trials of novel agents in ES.

Original languageEnglish
Article numbere180219
JournalJAMA oncology
Volume4
Issue number9
DOIs
Publication statusPublished - 2018 Sep 1
Externally publishedYes

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gemcitabine
Anthracyclines
Sarcoma
Disease-Free Survival
Benchmarking
pazopanib

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Frezza, A. M., Jones, R. L., Vullo, S. L., Asano, N., Lucibello, F., Ben-Ami, E., ... Stacchiotti, S. (2018). Anthracycline, gemcitabine, and pazopanib in epithelioid sarcoma a multi-institutional case series. JAMA oncology, 4(9), [e180219]. https://doi.org/10.1001/jamaoncol.2018.0219

Anthracycline, gemcitabine, and pazopanib in epithelioid sarcoma a multi-institutional case series. / Frezza, Anna Maria; Jones, Robin L.; Vullo, Salvatore Lo; Asano, Naofumi; Lucibello, Francesca; Ben-Ami, Eytan; Ratan, Ravin; Teterycz, Pawel; Boye, Kjetil; Brahmi, Mehdi; Palmerini, Emanuela; Fedenko, Alexander; Vincenzi, Bruno; Brunello, Antonella; Desar, Ingrid M.E.; Benjamin, Robert S.; Blay, Jean Yves; Broto, Javier Martin; Casali, Paolo G.; Gelderblom, Hans; Grignani, Giovanni; Gronchi, Alessandro; Hall, Kirsten Sundby; Mir, Olivier; Rutkowski, Piotr; Wagner, Andrew J.; Anurova, Olga; Collini, Paola; Tos, Angelo P.Dei; Flucke, Uta; Hornick, Jason L.; Lobmaier, Ingvild; Philippe, Terrier; Picci, Piero; Ranchere, Dominique; Renne, Salvatore L.; Sbaraglia, Marta; Thway, Khin; Wagrodzki, Michal; Wang, Wei Lien; Yoshida, Akihiko; Mariani, Luigi; Kawai, Akira; Stacchiotti, Silvia.

In: JAMA oncology, Vol. 4, No. 9, e180219, 01.09.2018.

Research output: Contribution to journalArticle

Frezza, AM, Jones, RL, Vullo, SL, Asano, N, Lucibello, F, Ben-Ami, E, Ratan, R, Teterycz, P, Boye, K, Brahmi, M, Palmerini, E, Fedenko, A, Vincenzi, B, Brunello, A, Desar, IME, Benjamin, RS, Blay, JY, Broto, JM, Casali, PG, Gelderblom, H, Grignani, G, Gronchi, A, Hall, KS, Mir, O, Rutkowski, P, Wagner, AJ, Anurova, O, Collini, P, Tos, APD, Flucke, U, Hornick, JL, Lobmaier, I, Philippe, T, Picci, P, Ranchere, D, Renne, SL, Sbaraglia, M, Thway, K, Wagrodzki, M, Wang, WL, Yoshida, A, Mariani, L, Kawai, A & Stacchiotti, S 2018, 'Anthracycline, gemcitabine, and pazopanib in epithelioid sarcoma a multi-institutional case series', JAMA oncology, vol. 4, no. 9, e180219. https://doi.org/10.1001/jamaoncol.2018.0219
Frezza, Anna Maria ; Jones, Robin L. ; Vullo, Salvatore Lo ; Asano, Naofumi ; Lucibello, Francesca ; Ben-Ami, Eytan ; Ratan, Ravin ; Teterycz, Pawel ; Boye, Kjetil ; Brahmi, Mehdi ; Palmerini, Emanuela ; Fedenko, Alexander ; Vincenzi, Bruno ; Brunello, Antonella ; Desar, Ingrid M.E. ; Benjamin, Robert S. ; Blay, Jean Yves ; Broto, Javier Martin ; Casali, Paolo G. ; Gelderblom, Hans ; Grignani, Giovanni ; Gronchi, Alessandro ; Hall, Kirsten Sundby ; Mir, Olivier ; Rutkowski, Piotr ; Wagner, Andrew J. ; Anurova, Olga ; Collini, Paola ; Tos, Angelo P.Dei ; Flucke, Uta ; Hornick, Jason L. ; Lobmaier, Ingvild ; Philippe, Terrier ; Picci, Piero ; Ranchere, Dominique ; Renne, Salvatore L. ; Sbaraglia, Marta ; Thway, Khin ; Wagrodzki, Michal ; Wang, Wei Lien ; Yoshida, Akihiko ; Mariani, Luigi ; Kawai, Akira ; Stacchiotti, Silvia. / Anthracycline, gemcitabine, and pazopanib in epithelioid sarcoma a multi-institutional case series. In: JAMA oncology. 2018 ; Vol. 4, No. 9.
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title = "Anthracycline, gemcitabine, and pazopanib in epithelioid sarcoma a multi-institutional case series",
abstract = "IMPORTANCE Epithelioid sarcoma (ES) is an exceedingly rare malignant neoplasm with distinctive pathologic, molecular, and clinical features as well as the potential to respond to new targeted drugs. Little is known on the activity of anthracycline-based regimens, gemcitabine-based regimens, and pazopanib in this disease. OBJECTIVE To report on the activity of anthracycline-based regimens, gemcitabine-based regimens, and pazopanib in patients with advanced ES. DESIGN, SETTING, AND PARTICIPANTS Seventeen sarcoma reference centers in Europe, the United States, and Japan contributed data to this retrospective analysis of patients with locally advanced/metastatic ES diagnosed between 1990 and 2016. Local pathological review was performed in all cases to confirm diagnosis according to most recent criteria. EXPOSURES All patients included in the study received anthracycline-based regimens, gemcitabine-based regimens, or pazopanib. MAIN OUTCOME AND MEASURES Responsewas assessed by RECIST. Progression-free survival (PFS) and overall survival (OS) were computed by Kaplan-Meier method. Classic and proximal subtypes were defined based on morphology (according to 2013World Health Organization guidelines). RESULTS Overall, 115 patients were included, 80 (70{\%}) were men and 35 (30{\%}) were women, with a median age of 32 years (range, 15-77 years). Of the 115 patients with ES, 85 were treated with anthracycline-based regimens, 41 with gemcitabine-based regimens, and 18 with pazopanib. Twenty-four received more than 1 treatment. Median follow-up was 34 months. Response rate for anthracycline-based regimens was 22{\%}, with a median PFS of 6 months. One complete response (CR) was reported. A trend toward a higher response rate was noticed in morphological proximal type (26{\%}) vs classic type (19{\%}) and in proximal vs distal primary site (26{\%}vs 18{\%}). The response rate for gemcitabine-based regimens was 27{\%}, with 2 CR and a median PFS of 4 months. In this group, a trend toward a higher response rate was reported in classic vs proximal morphological type (30{\%} vs 22{\%}) and in distal vs proximal primary site (40{\%} vs 14{\%}). In the pazopanib group, no objective responses were seen, and median PFS was 3 months. CONCLUSIONS AND RELEVANCE This is the largest retrospective series of systemic therapy in ES.We confirm a moderate activity of anthracycline-based and gemcitabine-based regimens in ES, with a similar response rate and PFS in both groups. The value of pazopanib was low. These data may serve as a benchmark for trials of novel agents in ES.",
author = "Frezza, {Anna Maria} and Jones, {Robin L.} and Vullo, {Salvatore Lo} and Naofumi Asano and Francesca Lucibello and Eytan Ben-Ami and Ravin Ratan and Pawel Teterycz and Kjetil Boye and Mehdi Brahmi and Emanuela Palmerini and Alexander Fedenko and Bruno Vincenzi and Antonella Brunello and Desar, {Ingrid M.E.} and Benjamin, {Robert S.} and Blay, {Jean Yves} and Broto, {Javier Martin} and Casali, {Paolo G.} and Hans Gelderblom and Giovanni Grignani and Alessandro Gronchi and Hall, {Kirsten Sundby} and Olivier Mir and Piotr Rutkowski and Wagner, {Andrew J.} and Olga Anurova and Paola Collini and Tos, {Angelo P.Dei} and Uta Flucke and Hornick, {Jason L.} and Ingvild Lobmaier and Terrier Philippe and Piero Picci and Dominique Ranchere and Renne, {Salvatore L.} and Marta Sbaraglia and Khin Thway and Michal Wagrodzki and Wang, {Wei Lien} and Akihiko Yoshida and Luigi Mariani and Akira Kawai and Silvia Stacchiotti",
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T1 - Anthracycline, gemcitabine, and pazopanib in epithelioid sarcoma a multi-institutional case series

AU - Frezza, Anna Maria

AU - Jones, Robin L.

AU - Vullo, Salvatore Lo

AU - Asano, Naofumi

AU - Lucibello, Francesca

AU - Ben-Ami, Eytan

AU - Ratan, Ravin

AU - Teterycz, Pawel

AU - Boye, Kjetil

AU - Brahmi, Mehdi

AU - Palmerini, Emanuela

AU - Fedenko, Alexander

AU - Vincenzi, Bruno

AU - Brunello, Antonella

AU - Desar, Ingrid M.E.

AU - Benjamin, Robert S.

AU - Blay, Jean Yves

AU - Broto, Javier Martin

AU - Casali, Paolo G.

AU - Gelderblom, Hans

AU - Grignani, Giovanni

AU - Gronchi, Alessandro

AU - Hall, Kirsten Sundby

AU - Mir, Olivier

AU - Rutkowski, Piotr

AU - Wagner, Andrew J.

AU - Anurova, Olga

AU - Collini, Paola

AU - Tos, Angelo P.Dei

AU - Flucke, Uta

AU - Hornick, Jason L.

AU - Lobmaier, Ingvild

AU - Philippe, Terrier

AU - Picci, Piero

AU - Ranchere, Dominique

AU - Renne, Salvatore L.

AU - Sbaraglia, Marta

AU - Thway, Khin

AU - Wagrodzki, Michal

AU - Wang, Wei Lien

AU - Yoshida, Akihiko

AU - Mariani, Luigi

AU - Kawai, Akira

AU - Stacchiotti, Silvia

PY - 2018/9/1

Y1 - 2018/9/1

N2 - IMPORTANCE Epithelioid sarcoma (ES) is an exceedingly rare malignant neoplasm with distinctive pathologic, molecular, and clinical features as well as the potential to respond to new targeted drugs. Little is known on the activity of anthracycline-based regimens, gemcitabine-based regimens, and pazopanib in this disease. OBJECTIVE To report on the activity of anthracycline-based regimens, gemcitabine-based regimens, and pazopanib in patients with advanced ES. DESIGN, SETTING, AND PARTICIPANTS Seventeen sarcoma reference centers in Europe, the United States, and Japan contributed data to this retrospective analysis of patients with locally advanced/metastatic ES diagnosed between 1990 and 2016. Local pathological review was performed in all cases to confirm diagnosis according to most recent criteria. EXPOSURES All patients included in the study received anthracycline-based regimens, gemcitabine-based regimens, or pazopanib. MAIN OUTCOME AND MEASURES Responsewas assessed by RECIST. Progression-free survival (PFS) and overall survival (OS) were computed by Kaplan-Meier method. Classic and proximal subtypes were defined based on morphology (according to 2013World Health Organization guidelines). RESULTS Overall, 115 patients were included, 80 (70%) were men and 35 (30%) were women, with a median age of 32 years (range, 15-77 years). Of the 115 patients with ES, 85 were treated with anthracycline-based regimens, 41 with gemcitabine-based regimens, and 18 with pazopanib. Twenty-four received more than 1 treatment. Median follow-up was 34 months. Response rate for anthracycline-based regimens was 22%, with a median PFS of 6 months. One complete response (CR) was reported. A trend toward a higher response rate was noticed in morphological proximal type (26%) vs classic type (19%) and in proximal vs distal primary site (26%vs 18%). The response rate for gemcitabine-based regimens was 27%, with 2 CR and a median PFS of 4 months. In this group, a trend toward a higher response rate was reported in classic vs proximal morphological type (30% vs 22%) and in distal vs proximal primary site (40% vs 14%). In the pazopanib group, no objective responses were seen, and median PFS was 3 months. CONCLUSIONS AND RELEVANCE This is the largest retrospective series of systemic therapy in ES.We confirm a moderate activity of anthracycline-based and gemcitabine-based regimens in ES, with a similar response rate and PFS in both groups. The value of pazopanib was low. These data may serve as a benchmark for trials of novel agents in ES.

AB - IMPORTANCE Epithelioid sarcoma (ES) is an exceedingly rare malignant neoplasm with distinctive pathologic, molecular, and clinical features as well as the potential to respond to new targeted drugs. Little is known on the activity of anthracycline-based regimens, gemcitabine-based regimens, and pazopanib in this disease. OBJECTIVE To report on the activity of anthracycline-based regimens, gemcitabine-based regimens, and pazopanib in patients with advanced ES. DESIGN, SETTING, AND PARTICIPANTS Seventeen sarcoma reference centers in Europe, the United States, and Japan contributed data to this retrospective analysis of patients with locally advanced/metastatic ES diagnosed between 1990 and 2016. Local pathological review was performed in all cases to confirm diagnosis according to most recent criteria. EXPOSURES All patients included in the study received anthracycline-based regimens, gemcitabine-based regimens, or pazopanib. MAIN OUTCOME AND MEASURES Responsewas assessed by RECIST. Progression-free survival (PFS) and overall survival (OS) were computed by Kaplan-Meier method. Classic and proximal subtypes were defined based on morphology (according to 2013World Health Organization guidelines). RESULTS Overall, 115 patients were included, 80 (70%) were men and 35 (30%) were women, with a median age of 32 years (range, 15-77 years). Of the 115 patients with ES, 85 were treated with anthracycline-based regimens, 41 with gemcitabine-based regimens, and 18 with pazopanib. Twenty-four received more than 1 treatment. Median follow-up was 34 months. Response rate for anthracycline-based regimens was 22%, with a median PFS of 6 months. One complete response (CR) was reported. A trend toward a higher response rate was noticed in morphological proximal type (26%) vs classic type (19%) and in proximal vs distal primary site (26%vs 18%). The response rate for gemcitabine-based regimens was 27%, with 2 CR and a median PFS of 4 months. In this group, a trend toward a higher response rate was reported in classic vs proximal morphological type (30% vs 22%) and in distal vs proximal primary site (40% vs 14%). In the pazopanib group, no objective responses were seen, and median PFS was 3 months. CONCLUSIONS AND RELEVANCE This is the largest retrospective series of systemic therapy in ES.We confirm a moderate activity of anthracycline-based and gemcitabine-based regimens in ES, with a similar response rate and PFS in both groups. The value of pazopanib was low. These data may serve as a benchmark for trials of novel agents in ES.

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