Examining Stripes on a Herd of Zebras: Impact of Genomic Matching for Ultrarare Sarcomas in Phase 1 Clinical Trials (SAMBA 102)

Authors

Justin T Moyers
Roberto Carmagnani Pestana
Jason Roszik
David S Hong
Aung Naing
Siqing Fu
Sarina Piha-Paul
Timothy A Yap
Daniel Karp
Jordi Rodon
Andy Livingston
Maria Alejandra Zarzour
Vinod Ravi
Shreyaskumar Patel
Robert S Benjamin
Joseph Ludwig
Cynthia Herzog
Ravin Ratan
Neeta Somaiah
Anthony Conley
Richard Gorlick
Funda Meric-Bernstam
Vivek Subbiah

Publication Date

1-17-2023

Journal

Clinical Cancer Research

Abstract

Purpose: Recently, the Connective Tissue Oncology Society published consensus guidelines for recognizing ultrarare sarcomas (URS), defined as sarcomas with an incidence ≤1 per 1,000,000. We assessed the outcomes of 56 patients with soft tissue, and 21 with bone sarcomas, enrolled in Phase 1 trials.

Experimental design: In this Sarcoma-Matched Biomarker Analysis (SAMBA-102 study), we reviewed records from patients on Phase 1 trials at the University of Texas MD Anderson Cancer Center between January 2013 and June 2021.

Results: Among 587 sarcomas, 106 (18.1%) were classified as URS. Fifty (47%) were male, and the median age was 44.3 years (range, 19-82). The most common subtypes were alveolar soft part sarcoma (ASPS), chordoma, dedifferentiated chondrosarcoma, and sclerosing epithelioid fibrosarcoma. Compared with common sarcomas, median OS was similar 16.1 months [95% confidence interval (CI), 13.6-17.5] versus 16.1 (95% CI, 8.2-24.0) in URS (P = 0.359). Objective response to treatment was higher in URS 13.2% (n = 14/106) compared with common sarcomas 6.9% (n = 33/481; P = 0.029). Median OS for those treated on matched trials was 27.3 months (95% CI, 1.9-52.7) compared with 13.4 months (95% CI, 6.3-20.6) for those not treated on matched trials (P = 0.291). Eight of 33 (24%) molecularly matched treatments resulted in an objective response, whereas 6 of 73 unmatched treatments (8.2%) resulted in an objective response (P = 0.024). Clinical benefit rate was 36.4% (12/33) in matched trials versus 26.0% (19/73) in unmatched trials (P = 0.279).

Conclusions: The results demonstrate the benefit of genomic selection in Phase 1 trials to help identify molecular subsets likely to benefit from targeted therapy.

Keywords

Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Young Adult, Bone Neoplasms, Genomics, Osteosarcoma, Sarcoma, Alveolar Soft Part

DOI

10.1158/1078-0432.CCR-22-2509

PMID

36288393

PMCID

PMC9843435

PubMedCentral® Posted Date

10-26-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes