Journal article
Safety and efficacy of pembrolizumab, radiation therapy, and surgery versus radiation therapy and surgery for stage III soft tissue sarcoma of the extremity (SU2C-SARC032): an open-label, randomised clinical trial
The Lancet (British edition), Vol.404(10467), pp.2053-2064
11/2024
DOI: 10.1016/S0140-6736(24)01812-9
PMCID: PMC11842127
PMID: 39547252
Abstract
Approximately half of patients with localised, high-risk soft tissue sarcoma of the extremity develop metastases. We aimed to assess whether the addition of pembrolizumab to preoperative radiotherapy and surgery would improve disease-free survival.
We completed an open-label, randomised clinical trial in patients with grade 2 or 3, stage III undifferentiated pleomorphic sarcoma or dedifferentiated or pleomorphic liposarcoma of the extremity and limb girdle. Patients were enrolled at 20 academic institutions in Australia, Canada, Italy, and the USA. Patients were randomly assigned to preoperative radiotherapy then surgery (control group) or preoperative pembrolizumab with radiotherapy (initiated 1–14 days after the first dose of pembrolizumab) then surgery and postoperative pembrolizumab (experimental group). Pembrolizumab (200 mg intravenously every 3 weeks) was administered as three neoadjuvant cycles (before, during, and after radiotherapy) and 14 or less adjuvant cycles. Primary endpoint was disease-free survival. This study is registered with ClincialTrials.gov (NCT03092323).
Between Nov 18, 2017, and Nov 14, 2023, 143 participants were randomly assigned to treatment. A modified intention-to-treat analysis of 127 patients with median follow-up of 43 months showed that the experimental group (n=64) had significantly longer disease-free survival than the control group (n=63; log-rank one-sided p=0·035; hazard ratio [HR] 0·61; 90% CI 0·39–0·96). The 2-year disease-free survival increased by 15% with addition of pembrolizumab: 52% (90% CI 42–64) and 67% (90% CI 58–78) for the control and experimental groups, respectively. Disease-free survival was similarly improved with pembrolizumab for the intention-to-treat patient population (HR 0·61 [90% CI 0·39–0·95]). Grade 3 or higher adverse events occurred more frequently in the experimental group (56%) than the control group (31%).
Addition of pembrolizumab to preoperative radiotherapy and surgery improves disease-free survival for patients with stage III undifferentiated pleomorphic sarcoma and pleomorphic or dedifferentiated liposarcoma of the extremity, which establishes a promising new treatment option for these patients.
Stand Up to Cancer and Merck Sharp & Dohme.
Details
- Title: Subtitle
- Safety and efficacy of pembrolizumab, radiation therapy, and surgery versus radiation therapy and surgery for stage III soft tissue sarcoma of the extremity (SU2C-SARC032): an open-label, randomised clinical trial
- Creators
- Yvonne M Mowery - Duke UniversityKarla V Ballman - Mayo Clinic in FloridaAngela M Hong - Chris O’Brien LifehouseScott M Schuetze - University of MichiganAndrew J Wagner - Dana-Farber Cancer InstituteVarun Monga - University of IowaRachel S Heise - Cornell UniversitySteven Attia - Mayo Clinic in FloridaEdwin Choy - Massachusetts General HospitalMelissa A Burgess - UPMC Hillman Cancer CenterSusie Bae - Peter MacCallum Cancer CentreDavid I Pryor - Princess Alexandra HospitalBrian A Van Tine - Washington University in St. LouisGabriel Tinoco - The Ohio State UniversityBartosz Chmielowski - University of California, Los AngelesCarolyn Freeman - McGill University Health CentreAlessandro Gronchi - Fondazione IRCCS Istituto Nazionale dei TumoriChristian F Meyer - Johns Hopkins UniversityMark A Dickson - Memorial Sloan Kettering Cancer CenterLee Hartner - University of PennsylvaniaLara E Davis - Oregon Health & Science UniversityBenjamin C Powers - The University of Kansas Cancer CenterEverett J Moding - Stanford UniversityKent J Weinhold - Duke UniversityMatt van de Rijn - Stanford UniversityBrian E Brigman - Duke UniversityRichard F Riedel - Duke Medical CenterDavid G Kirsch - Duke University
- Resource Type
- Journal article
- Publication Details
- The Lancet (British edition), Vol.404(10467), pp.2053-2064
- DOI
- 10.1016/S0140-6736(24)01812-9
- PMID
- 39547252
- PMCID
- PMC11842127
- NLM abbreviation
- Lancet
- ISSN
- 0140-6736
- eISSN
- 1474-547X
- Publisher
- Elsevier Ltd
- Grant note
- SU2C Merck Catalyst grantMerck Investigator Studies Program grant (MSD)Cancer AustraliaGPA Andrew Ursini Charitable Fund: K08DE029887 National Institutes of Health [NIH] ): R35CA197616 NIH)National Cancer Institutes of Health: P30CA046592
This study was funded by a SU2C Merck Catalyst grant to DGK and a Merck Investigator Studies Program grant (MSD) to DGK. Funding for the Australian sites included the Australian and New Zealand Sarcoma Association, Cancer Australia, and GPA Andrew Ursini Charitable Fund. YMM was supported by K08DE029887 (National Institutes of Health [NIH] ) , and DGK was supported by R35CA197616 (NIH) . Research reported in this publication was also supported by the National Cancer Institutes of Health under award number P30CA046592. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. We thank Denise Reinke, Steven Young, Scott Okuno, and the research coordinators at SARC for supporting this trial by collecting patient data and samples, and for providing oversight of the study. In particular, we thank Erin Kozlowski, who provided expert project management at SARC. We also thank the multidisciplinary team members and the clinical research teams at each of the participating sites, who enrolled patients to make this international trial possible. Finally, we thank the patients and their caregivers for their participation in this trial.
- Language
- English
- Electronic publication date
- 11/12/2024
- Date published
- 11/2024
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984747817102771
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