Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial

Tawbi, Hussein A.; Burgess, Melissa; Bolejack, Vanessa; Tine, Brian A. Van; Schuetze, Scott M.; Hu, James; D’Angelo, Sandra P.; Attia, Steven; Riedel, Richard F.; Priebat, Dennis A.; Movva, Sujana; Davis, Lara E.; Okuno, Scott H.; Reed, Damon R.; Crowley, John; Butterfield, Lisa H.; Salazar, Ruth; Rodriguez‐Canales, Jaime; Lazar, Alexander J.; Wistuba, Ignacio I.; Baker, Laurence H.; Maki, Robert G.; Reinke, Denise K.; Patel, Shreyaskumar

doi:10.1016/s1470-2045(17)30624-1

Cited by 979 publications

(947 citation statements)

References 36 publications

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“…The first trials of ICIs have only recently been completed in sarcoma, with reported response rates of <20% with either pembrolizumab monotherapy or combination ipilimumab/nivolumab . These outcomes are consistent with those observed from checkpoint inhibitors in other trials of solid tumors with unselected patients.…”

Section: Sarcomas—a Framework For Approaching Modern Immunotherapysupporting

confidence: 70%

“…We conducted a phase II trial of combined axitinib and pembrolizumab for advanced soft tissue sarcomas, which produced objective responses in 54.5% of the 11 evaluable patients with ASPS, greater than would be expected with either axitinib monotherapy or single agent PD‐1 blockade . While other sarcoma subtypes including HGUPS and dedifferentiated liposarcomas have previously been reported to respond to pembrolizumab monotherapy, we observed limited activity in these subtypes, with some patients demonstrating more rapid progression of disease with combination axitinib/pembrolizumab. Ongoing analysis of correlative immunoprofiling and circulating angiogenic factors may help to clarify the mechanism for these hyper‐progressing patients.…”

Section: Sarcomas—a Framework For Approaching Modern Immunotherapymentioning

confidence: 91%

“…These outcomes are consistent with those observed from checkpoint inhibitors in other trials of solid tumors with unselected patients. However, meaningful and durable responses to checkpoint blockade have been observed in certain subtypes including HGUPS, dedifferentiated liposarcoma, ASPS, clear cell sarcoma, and cutaneous angiosarcomas …”

Section: Sarcomas—a Framework For Approaching Modern Immunotherapymentioning

confidence: 99%

“…We previously treated a patient with refractory synovial sarcoma who had received prior NY‐ESO‐1 engineered TCRs with response several years previously with a combination of the VEGF receptor TKI axitinib plus pembrolizumab . While synovial sarcomas rarely respond to either CTLA‐4 or PD‐1 monotherapy, this patient achieved stable disease on axitinib/pembrolizumab for 32 weeks. Overall, while compelling rationale is present for augmenting efficacy of adoptive cellular therapies with checkpoint blockade, many questions still remain for optimal use of this combination strategy.…”

Section: Sarcomas—a Framework For Approaching Modern Immunotherapymentioning

confidence: 99%

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Immune checkpoint inhibitors: The linchpins of modern immunotherapy

Wilky

2019

Immunological Reviews

156

113

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Immune checkpoint inhibitors (ICIs) have revolutionized our approach to cancer treatment in the past decade. While monoclonal antibodies to CTLA‐4 and PD‐1/PD‐L1 have produced remarkable and durable responses in a subset of patients, the majority of patients will still develop primary or adaptive resistance. With complex mechanisms of resistance limiting the efficacy of checkpoint inhibitor monotherapy, it is critical to develop combination approaches to allow more patients to benefit from immunotherapy. In this review, I approach the current landscape of ICI research from the perspective of sarcomas, a rare group of bone and soft tissue cancers that have had limited benefit from checkpoint inhibitor monotherapy, and little investigation of biomarkers to predict responses. By surveying the various mechanisms of resistance and treatment modalities being explored in other solid tumors, I outline how ICIs will undoubtedly serve as the critical foundation for future directions in modern immunotherapy.

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Section: Sarcomas—a Framework For Approaching Modern Immunotherapysupporting

confidence: 70%

Section: Sarcomas—a Framework For Approaching Modern Immunotherapymentioning

confidence: 91%

Section: Sarcomas—a Framework For Approaching Modern Immunotherapymentioning

confidence: 99%

Section: Sarcomas—a Framework For Approaching Modern Immunotherapymentioning

confidence: 99%

See 2 more Smart Citations

Immune checkpoint inhibitors: The linchpins of modern immunotherapy

Wilky

2019

Immunological Reviews

156

113

View full text Add to dashboard Cite

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“…What models can we use to study these questions? 81 In the pediatric trial of nivolumab alone or in combination with ipilumumab, no objective responses were seen in patients with OS. 71 In recent years, the recognition of extreme genomic complexity of OS 72,73 has led many to believe that a higher tumor mutational burden and neo-epitope antigen generation should suggest response to immune therapies such as immune checkpoint inhibition.…”

Section: Intentmentioning

confidence: 99%

Provocative questions in osteosarcoma basic and translational biology: A report from the Children's Oncology Group

Roberts

Lizardo

Reed

et al. 2019

Cancer

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Patients who are diagnosed with osteosarcoma (OS) today receive the same therapy that patients have received over the last 4 decades. Extensive efforts to identify more effective or less toxic regimens have proved disappointing. As we enter a postgenomic era in which we now recognize OS not as a cancer of mutations but as one defined by p53 loss, chromosomal complexity, copy number alteration, and profound heterogeneity, emerging threads of discovery leave many hopeful that an improving understanding of biology will drive discoveries that improve clinical care. Under the organization of the Bone Tumor Biology Committee of the Children's Oncology Group, a team of clinicians and scientists sought to define the state of the science and to identify questions that, if answered, have the greatest potential to drive fundamental clinical advances. Having discussed these questions in a series of meetings, each led by invited experts, we distilled these conversations into a series of seven Provocative Questions. These include questions about the molecular events that trigger oncogenesis, the genomic and epigenomic drivers of disease, the biology of lung metastasis, research models that best predict clinical outcomes, and processes for translating findings into clinical trials. Here, we briefly present each Provocative Question, review the current scientific evidence, note the immediate opportunities, and speculate on the impact that answered questions might have on the field. We do so with an intent to provide a framework around which investigators can build programs and collaborations to tackle the hardest problems and to establish research priorities for those developing policies and providing funding. Cancer 2019;125:3514-3525.

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Exploration of Immune-Related Gene Expression in Osteosarcoma and Association With Outcomes

Liu

Xie

et al. 2021

JAMA Netw Open

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Key Points Question What is the immunogenomic landscape of osteosarcoma? Findings In this genetic association study based on 84 samples from The Cancer Genome Atlas, 14 immune-related genes associated with survival in osteosarcoma were identified. Meaning These findings suggest that a diagnostic risk score based on immune-related gene expression profiles may be useful to planning individualized therapies for osteosarcoma.

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Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial

Abstract: Merck, SARC, Sarcoma Foundation of America, QuadW Foundation, Pittsburgh Cure Sarcoma, and Ewan McGregor.

Cited by 979 publications

References 36 publications

Immune checkpoint inhibitors: The linchpins of modern immunotherapy

Immune checkpoint inhibitors: The linchpins of modern immunotherapy

Provocative questions in osteosarcoma basic and translational biology: A report from the Children's Oncology Group

Exploration of Immune-Related Gene Expression in Osteosarcoma and Association With Outcomes

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