Updates from ASCO: Sarcoma

Educational Objectives

The goal of this program is to improve the management of sarcoma. After hearing and assimilating this program, the clinician will be better able to:

1. Optimize management of patients with high-risk soft-tissue sarcoma using systemic therapy.

Summary

Vimseltinib for Tenosynovial Giant Cell Tumor (TGCT)

TGCT treatment options: surgery is the primary treatment; the risk for recurrence after surgery is high; TGCT occurs from an overproduction of colony-stimulating factor 1 (CSF1); pexidartinib, a CSF1 inhibitor, was approved in 2019 for symptomatic TGCT with severe disease or significant functional limitations not amenable to surgery (the ENLIVEN trial; Tap et al [2019])

MOTION trial (Tap et al [2024]): vimseltinib yielded an objective response rate of 33% (vs 0% with placebo) and significant antitumor activity; vimseltinib significantly improved range of motion, physical function, stiffness, and pain; 40% of participants reported improvements in ≥3 of the clinical outcomes irrespective of actual tumor response; it was well tolerated with few discontinuations; no evidence of cholestatic hepatotoxicity or drug-induced liver injury (a black box warning for pexidartinib) was observed

StrateGIST Study (Schoffski et al [2024])

IDRX-42 for gastrointestinal stromal tumors (GIST): in the phase 1 study, IDRX-42 was used to manage patients with metastatic or unresectable GIST with pathologic mutations in KIT or non-exon 18 PDGFRA and ≥3 lines of previous therapy

Results: IDRX-42 exhibited a favorable safety profile; ≈19% of patients had grade 3 or 4 treatment-related adverse events, eg, diarrhea, fatigue, and anemia; patients were able to continue on treatment with either dose reductions or breaks; IDRX-42 had significant antitumor activity in the heavily pretreated population; IDRX-42 has demonstrated promising clinical activity following resistance to prior tyrosine kinase inhibitors; antitumor activity was observed in patients with activating mutations in KIT exons 9 and 11, as well as resistance mutations in exons 13 and 17; a dose of 300 mg has been established for further studies

New-Treatment Option for High-Risk Sarcoma

Current management of sarcoma: localized soft tissue sarcomas are managed with surgery and neoadjuvant radiation therapy; local control rates are good (90%); however, risk for distant or metastatic disease is ≤50% for patients with high-risk features; pembrolizumab showed encouraging signal of activity in patients with undifferentiated pleomorphic sarcoma (UPS) and liposarcoma in the SARK028 study (Tawbi et al [2017])

SU2C-SARC032 study (Mowery et al [2024]): the addition of pembrolizumab to preoperative-radiotherapy and surgery increased disease-free survival in patients with grade 2 or 3 UPS or liposarcoma (>5 cm); benefit appeared to be greater in grade 3 disease; the study establishes addition of pembrolizumab to preoperative radiotherapy and surgery as a new treatment option for high-risk soft tissue sarcomas

Readings

Mowery YM, Ballman KV, Hong AM, et al. SU2C-SARC032: A randomized trial of neoadjuvant RT and surgery with or without pembrolizumab for soft tissue sarcoma. J Clin Oncol. 2024;42(16_suppl):11504-11504. doi:https://doi.org/10.1200/jco.2024.42.16_suppl.11504; Schoffski P, Heinrich MC, Trent JC, et al. StrateGIST 1: A first-in-human (FIH), phase 1 study of IDRX-42 in patients with metastatic gastrointestinal stromal tumors resistant to prior treatment with tyrosine kinase inhibitors (TKIs). J Clin Oncol. 2024;42(16_suppl):11501-11501. doi:https://doi.org/10.1200/jco.2024.42.16_suppl.11501; Tap WD, Gelderblom H, Palmerini E, et al. Pexidartinib versus placebo for advanced tenosynovial giant cell tumour (ENLIVEN): a randomised phase 3 trial. Lancet. 2019;394(10197):478-487. doi:10.1016/S0140-6736(19)30764-0; Tap WD, Sharma MG, Vallee M, et al. The MOTION study: a randomized, phase III study of vimseltinib for the treatment of tenosynovial giant cell tumor. Future Oncol. 2024;20(10):593-601. doi:10.2217/fon-2023-0238; Tawbi HA, Burgess M, Bolejack V, et al. Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial [published correction appears in Lancet Oncol. 2017 Dec;18(12):e711. doi: 10.1016/S1470-2045(17)30864-1] [published correction appears in Lancet Oncol. 2018 Jan;19(1):e8. doi: 10.1016/S1470-2045(17)30926-9]. Lancet Oncol. 2017;18(11):1493-1501. doi:10.1016/S1470-2045(17)30624-1.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose. Dr. Chin's lecture contains information related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Chin was recorded at the Annual Practice Updates in Hematology and Oncology, held on August 9, 2024, in Chicago, IL, and presented by University of Chicago Pritzker School of Medicine. For information on upcoming CME activities from this presenter, please visit cme.chicago.edu. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0.50 CE contact hours.

Lecture ID:

ON160204

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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