Evaluation of Novel Targeted Therapies in Aggressive Biology Sarcoma Patients after progression from US FDA approved Therapies

Vivek Subbiah, Kenneth R. Hess, Muhammad Rizwan Khawaja, Michael J. Wagner, Chad Tang, Aung Naing, Siqing Fu, Filip Janku, Sarina Piha-Paul, Apostolia M. Tsimberidou, Cynthia E. Herzog, Joseph A. Ludwig, Shreyaskumar Patel, Vinod Ravi, Robert S. Benjamin, Funda Meric-Bernstam, David S. Hong

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Abstract

Prognosis of patients with advanced sarcoma after progression from FDA approved therapies remains grim. In this study, clinical outcomes of 100 patients with advanced sarcoma who received treatment on novel targeted therapy trials were evaluated. Outcomes of interest included best response, clinical benefit rate, progression-free survival (PFS) and overall survival (OS). Median patient age was 48 years (range 14-80). Patients had received a median of 2 prior lines of systemic treatment. Phase I treatments were anti-VEGF-based (n = 45), mTOR inhibitor-based (n = 15), and anti-VEGF + mTOR inhibitor-based (n = 17) or involved other targets (n = 23). Best responses included partial response (n = 4) and stable disease (n = 57). Clinical benefit rate was 36% (95% confidence interval 27-46%). Median OS was 9.6 months (95% Confidence Interval 8.1-14.2); median PFS was 3.5 months (95% Confidence Interval 2.4-4.7). RMH prognostic score of 2 or 3 was associated with lower median OS (log-rank p-value < 0.0001) and PFS (log-rank p-value 0.0081). Receiving cytotoxic chemotherapy as part of phase I trial was also associated with shorter median OS (log-rank p-value 0.039). Patients with advanced sarcoma treated on phase I clinical trials had a clinical benefit rate of 36% and RMH score predicted survival.

Original languageEnglish (US)
Article number35448
JournalScientific reports
Volume6
DOIs
StatePublished - Oct 17 2016

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Sarcoma
Survival
Disease-Free Survival
Confidence Intervals
Vascular Endothelial Growth Factor A
Therapeutics
Clinical Trials, Phase I
Drug Therapy

All Science Journal Classification (ASJC) codes

  • General

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Subbiah, V., Hess, K. R., Khawaja, M. R., Wagner, M. J., Tang, C., Naing, A., ... Hong, D. S. (2016). Evaluation of Novel Targeted Therapies in Aggressive Biology Sarcoma Patients after progression from US FDA approved Therapies. Scientific reports, 6, [35448]. https://doi.org/10.1038/srep35448
Subbiah, Vivek ; Hess, Kenneth R. ; Khawaja, Muhammad Rizwan ; Wagner, Michael J. ; Tang, Chad ; Naing, Aung ; Fu, Siqing ; Janku, Filip ; Piha-Paul, Sarina ; Tsimberidou, Apostolia M. ; Herzog, Cynthia E. ; Ludwig, Joseph A. ; Patel, Shreyaskumar ; Ravi, Vinod ; Benjamin, Robert S. ; Meric-Bernstam, Funda ; Hong, David S. / Evaluation of Novel Targeted Therapies in Aggressive Biology Sarcoma Patients after progression from US FDA approved Therapies. In: Scientific reports. 2016 ; Vol. 6.
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title = "Evaluation of Novel Targeted Therapies in Aggressive Biology Sarcoma Patients after progression from US FDA approved Therapies",
abstract = "Prognosis of patients with advanced sarcoma after progression from FDA approved therapies remains grim. In this study, clinical outcomes of 100 patients with advanced sarcoma who received treatment on novel targeted therapy trials were evaluated. Outcomes of interest included best response, clinical benefit rate, progression-free survival (PFS) and overall survival (OS). Median patient age was 48 years (range 14-80). Patients had received a median of 2 prior lines of systemic treatment. Phase I treatments were anti-VEGF-based (n = 45), mTOR inhibitor-based (n = 15), and anti-VEGF + mTOR inhibitor-based (n = 17) or involved other targets (n = 23). Best responses included partial response (n = 4) and stable disease (n = 57). Clinical benefit rate was 36{\%} (95{\%} confidence interval 27-46{\%}). Median OS was 9.6 months (95{\%} Confidence Interval 8.1-14.2); median PFS was 3.5 months (95{\%} Confidence Interval 2.4-4.7). RMH prognostic score of 2 or 3 was associated with lower median OS (log-rank p-value < 0.0001) and PFS (log-rank p-value 0.0081). Receiving cytotoxic chemotherapy as part of phase I trial was also associated with shorter median OS (log-rank p-value 0.039). Patients with advanced sarcoma treated on phase I clinical trials had a clinical benefit rate of 36{\%} and RMH score predicted survival.",
author = "Vivek Subbiah and Hess, {Kenneth R.} and Khawaja, {Muhammad Rizwan} and Wagner, {Michael J.} and Chad Tang and Aung Naing and Siqing Fu and Filip Janku and Sarina Piha-Paul and Tsimberidou, {Apostolia M.} and Herzog, {Cynthia E.} and Ludwig, {Joseph A.} and Shreyaskumar Patel and Vinod Ravi and Benjamin, {Robert S.} and Funda Meric-Bernstam and Hong, {David S.}",
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Subbiah, V, Hess, KR, Khawaja, MR, Wagner, MJ, Tang, C, Naing, A, Fu, S, Janku, F, Piha-Paul, S, Tsimberidou, AM, Herzog, CE, Ludwig, JA, Patel, S, Ravi, V, Benjamin, RS, Meric-Bernstam, F & Hong, DS 2016, 'Evaluation of Novel Targeted Therapies in Aggressive Biology Sarcoma Patients after progression from US FDA approved Therapies', Scientific reports, vol. 6, 35448. https://doi.org/10.1038/srep35448

Evaluation of Novel Targeted Therapies in Aggressive Biology Sarcoma Patients after progression from US FDA approved Therapies. / Subbiah, Vivek; Hess, Kenneth R.; Khawaja, Muhammad Rizwan; Wagner, Michael J.; Tang, Chad; Naing, Aung; Fu, Siqing; Janku, Filip; Piha-Paul, Sarina; Tsimberidou, Apostolia M.; Herzog, Cynthia E.; Ludwig, Joseph A.; Patel, Shreyaskumar; Ravi, Vinod; Benjamin, Robert S.; Meric-Bernstam, Funda; Hong, David S.

In: Scientific reports, Vol. 6, 35448, 17.10.2016.

Research output: Contribution to journalArticle

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AU - Subbiah, Vivek

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AU - Wagner, Michael J.

AU - Tang, Chad

AU - Naing, Aung

AU - Fu, Siqing

AU - Janku, Filip

AU - Piha-Paul, Sarina

AU - Tsimberidou, Apostolia M.

AU - Herzog, Cynthia E.

AU - Ludwig, Joseph A.

AU - Patel, Shreyaskumar

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AU - Benjamin, Robert S.

AU - Meric-Bernstam, Funda

AU - Hong, David S.

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