TY - JOUR
T1 - Impact of Biomarker-Matched Therapies on Outcomes in Patients with Sarcoma Enrolled in Early-Phase Clinical Trials (SAMBA 101)
AU - Pestana, Roberto Carmagnani
AU - Moyers, Justin T.
AU - Roszik, Jason
AU - Sen, Shiraj
AU - Hong, David S.
AU - Naing, Aung
AU - Herzog, Cynthia E.
AU - Fu, Siqing
AU - Piha-Paul, Sarina A.
AU - Rodon, Jordi
AU - Yap, Timothy A.
AU - Karp, Daniel D.
AU - Tsimberidou, Apostolia M.
AU - Pant, Shubham
AU - Zarzour, Maria A.
AU - Ratan, Ravin
AU - Ravi, Vinod
AU - Benjamin, Robert S.
AU - Lazar, Alexander J.
AU - Wang, Wei Lien
AU - Daw, Najat
AU - Gill, Jonathan B.
AU - Harrison, Douglas J.
AU - Lewis, Valerae O.
AU - Roland, Christina L.
AU - Patel, Shreyaskumar R.
AU - Livingston, J. Andrew
AU - Somaiah, Neeta
AU - Ludwig, Joseph A.
AU - Conley, Anthony P.
AU - Hamerschlak, Nelson
AU - Gorlick, Richard
AU - Meric-Bernstam, Funda
AU - Subbiah, Vivek
N1 - Publisher Copyright:
© 2023 The Authors.
PY - 2023/5/1
Y1 - 2023/5/1
N2 - Purpose: Developing new therapeutics for any of the more than 100 sarcoma subtypes presents a challenge. After progression from standard therapies, patients with sarcoma may be referred for enrollment in early-phase trials. This study aimed to investigate whether enrollment in biomarker-matched early-phase clinical trials leads to better outcomes for patients with advanced sarcoma. Experimental Design: In this retrospective analysis, investigational treatment characteristics and longitudinal survival outcomes were analyzed in patients with biopsy-confirmed sarcoma enrolled in early-phase trials at MD Anderson Cancer Center from May 2006 to July 2021. Results: Five hundred eighty-seven patients were included [405 soft tissue, 122 bone, 60 gastrointestinal stromal tumor (GIST); median of three prior lines of therapy]. Most common subtypes were leiomyosarcoma (17.2%), liposarcoma (14.0%), and GIST (10.2%). Molecular testing was available for 511 patients (87.1%); 221 patients (37.6%) were treated in matched trials. Overall response rate was 13.1% matched compared with 4.9% in unmatched (P < 0.001); the clinical benefit rate at 6 months was 43.9% vs. 19.9% (P < 0.001). Progression-free survival was longer for patients in matched trials (median, 5.5 vs. 2.4 months; P < 0.001), and overall survival was also superior for patients in matched trials (median, 21.5 vs. 12.3 months; P < 0.001). The benefit of enrollment in matched trials was maintained when patients with GIST were excluded from the analysis. Conclusions: Enrollment in biomarker-matched early-phase trials is associated with improved outcomes in heavily pretreated patients with metastatic sarcoma. Molecular testing of tumors from patients with advanced sarcoma and enrollment in matched trials is a reasonable therapeutic strategy.
AB - Purpose: Developing new therapeutics for any of the more than 100 sarcoma subtypes presents a challenge. After progression from standard therapies, patients with sarcoma may be referred for enrollment in early-phase trials. This study aimed to investigate whether enrollment in biomarker-matched early-phase clinical trials leads to better outcomes for patients with advanced sarcoma. Experimental Design: In this retrospective analysis, investigational treatment characteristics and longitudinal survival outcomes were analyzed in patients with biopsy-confirmed sarcoma enrolled in early-phase trials at MD Anderson Cancer Center from May 2006 to July 2021. Results: Five hundred eighty-seven patients were included [405 soft tissue, 122 bone, 60 gastrointestinal stromal tumor (GIST); median of three prior lines of therapy]. Most common subtypes were leiomyosarcoma (17.2%), liposarcoma (14.0%), and GIST (10.2%). Molecular testing was available for 511 patients (87.1%); 221 patients (37.6%) were treated in matched trials. Overall response rate was 13.1% matched compared with 4.9% in unmatched (P < 0.001); the clinical benefit rate at 6 months was 43.9% vs. 19.9% (P < 0.001). Progression-free survival was longer for patients in matched trials (median, 5.5 vs. 2.4 months; P < 0.001), and overall survival was also superior for patients in matched trials (median, 21.5 vs. 12.3 months; P < 0.001). The benefit of enrollment in matched trials was maintained when patients with GIST were excluded from the analysis. Conclusions: Enrollment in biomarker-matched early-phase trials is associated with improved outcomes in heavily pretreated patients with metastatic sarcoma. Molecular testing of tumors from patients with advanced sarcoma and enrollment in matched trials is a reasonable therapeutic strategy.
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U2 - 10.1158/1078-0432.CCR-22-3629
DO - 10.1158/1078-0432.CCR-22-3629
M3 - Article
C2 - 37058010
AN - SCOPUS:85159247840
SN - 1078-0432
VL - 29
SP - 1708
EP - 1718
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 9
ER -