Pazopanib therapy for desmoid tumors in adolescent and young adult patients

Agresta, Laura; Kim, Hee; Turpin, Brian; Nagarajan, Rajaram; Plemmons, Alexandra; Szabo, Sara; Dasgupta, Roshni; Sorger, Joel; Pressey, Joseph G.

doi:10.1002/pbc.26968

Cited by 24 publications

(17 citation statements)

References 34 publications

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“…11,12 The other clinical evidence is limited to a few prospective single-arm studies. [13][14][15] Moreover, most treatment regimens demonstrate inconsistent clinical responses, with less than 50% of patients typically responding to a given therapy. 8,13 Nirogacestat is a selective, noncompetitive, and reversible oral gamma-secretase inhibitor with preclinical data supporting NOTCHdependent inhibition.…”

Section: Discussionmentioning

confidence: 99%

Safety and efficacy of gamma‐secretase inhibitor nirogacestat (PF‐03084014) in desmoid tumor: Report of four pediatric/young adult cases

Takahashi

Prensner

Robson

et al. 2020

Pediatric Blood & Cancer

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Systemic therapy for pediatric desmoid tumors has been challenged by a lack of high‐quality clinical evidence and potential adverse effects. The gamma‐secretase inhibitor nirogacestat has shown promising efficacy in adults. We report four cases of pediatric and young adult desmoid tumor patients (three with familial adenomatous polyposis [FAP] syndrome) who received nirogacestat on compassionate use. After a median of 13.5 months (range 6‐18), three had durable benefit: a complete response (Case 1); a partial response (Case 2); stable disease (Case 3). The fourth had disease progression after a partial response. No patient experienced grade 3 or 4 adverse events.

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Section: Discussionmentioning

confidence: 99%

Safety and efficacy of gamma‐secretase inhibitor nirogacestat (PF‐03084014) in desmoid tumor: Report of four pediatric/young adult cases

Takahashi

Prensner

Robson

et al. 2020

Pediatric Blood & Cancer

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“…A phase II clinical study has shown apatinib’s encouraging efficacy for the treatment of metastatic sarcomas in adolescents and adults. 20 Pazopanib was shown to be effective in some case reports of pediatric osteosarcoma, 26 , 27 desmoid tumors 28 and synovial sarcoma. 29 However, clinical data on efficacy/safety of VEGFR-TKIs are still limited in the literature on pediatric patients.…”

Section: Discussionmentioning

confidence: 99%

<p>The Efficacy and Safety of Apatinib in Refractory/Relapse Advanced Pediatric Solid Tumor: A Retrospective Study</p>

Sun

Lü

Zhen

et al. 2020

CMAR

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Background: The prognosis of recurrent or refractory advanced childhood solid tumor patients is very poor and new therapeutic strategies are in urgent need. This study aimed to determine the efficacy and safety of apatinib in pediatric refractory/relapse advanced solid tumor patients. Patients and Methods: The study retrospectively reviewed recurrent or refractory advanced pediatric solid tumor patients who were treated with apatinib, an oral smallmolecule tyrosine kinase inhibitor (TKI) that targets vascular endothelial growth factor receptor-2 (VEGFR2), at the Sun Yat-sen University Cancer Center (China) from January 2016 to March 2019. Results: Fifty-six patients were included in the safety evaluation and 49 patients were included in the efficacy evaluation. The objective responses rate (ORR) was 26.5% (95% CI 15-41): 0 CR (complete response) and 13 PR (partial response). Disease control rate (DCR) (CR+PR+SD) was 79.6% (95% CI 65-90). The median progression-free survival (PFS) was 4.0 months (95% CI 2.6-5.4). There was no significant difference for ORR or PFS between the A (apatinib monotherapy), A+MT (apatinib combined with oral metronomic therapy) and A+SC (apatinib combined with salvage combination chemotherapy) group (p>0.05). The most common grade 3 or 4 adverse events were neutropenia (9[16.1%]), thrombocytopenia (8[14.3%]), hand-foot syndrome (3[5.4%]), hypertension (3[5.4%]), anaemia (3[5.4%]) and mucositis (2[3.6%]). Hypertension was the most serious adverse event and one death that occurred was considered as drug-related. Conclusion: Apatinib showed promising clinical activity in heavily treated recurrent or refractory advanced childhood solid tumor patients. However, it is necessary to pay special attention to monitoring blood pressure when using apatinib in children. Prospective randomized controlled clinical trial is warranted.

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“…A retrospective study by Szucs et al, described a partial response in three out of eight patients with DTF and stable disease in five out of eight patients with a median PFS of 13.5 months (128). Another retrospective study in adolescents and young adults with DTF by Agresta et al reported tumor reduction after pazopanib use with only mild toxicities (Table 2) (129). One clinical trial is currently ongoing to investigate TKIs in the setting of DTF; pazopanib (NCT01876082, phase 2 study) (Table 3) (134).…”

Section: The Pi3 Kinase/akt and Mtor Signaling Pathways In Desmoid-tymentioning

confidence: 99%

Activated Signaling Pathways and Targeted Therapies in Desmoid-Type Fibromatosis: A Literature Review

et al. 2019

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Desmoid-type fibromatosis (DTF) is a rare, soft tissue tumor of mesenchymal origin which is characterized by local infiltrative growth behavior. Besides “wait and see,” surgery and radiotherapy, several systemic treatments are available for symptomatic patients. Recently, targeted therapies are being explored in DTF. Unfortunately, effective treatment is still hampered by the limited knowledge of the molecular mechanisms that prompt DTF tumorigenesis. Many studies focus on Wnt/β-catenin signaling, since the vast majority of DTF tumors harbor a mutation in the CTNNB1 gene or the APC gene. The established role of the Wnt/β-catenin pathway in DTF forms an attractive therapeutic target, however, drugs targeting this pathway are still in an experimental stage and not yet available in the clinic. Only few studies address other signaling pathways which can drive uncontrolled growth in DTF such as: JAK/STAT, Notch, PI3 kinase/AKT, mTOR, Hedgehog, and the estrogen growth regulatory pathways. Evidence for involvement of these pathways in DTF tumorigenesis is limited and predominantly based on the expression levels of key pathway genes, or on observed clinical responses after targeted treatment. No clear driver role for these pathways in DTF has been identified, and a rationale for clinical studies is often lacking. In this review, we highlight common signaling pathways active in DTF and provide an up-to-date overview of their therapeutic potential.

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Pazopanib therapy for desmoid tumors in adolescent and young adult patients

Abstract: Pazopanib provides a promising, well-tolerated therapy for DT/AF in the AYA population and warrants further study.

Cited by 24 publications

References 34 publications

Safety and efficacy of gamma‐secretase inhibitor nirogacestat (PF‐03084014) in desmoid tumor: Report of four pediatric/young adult cases

Safety and efficacy of gamma‐secretase inhibitor nirogacestat (PF‐03084014) in desmoid tumor: Report of four pediatric/young adult cases

<p>The Efficacy and Safety of Apatinib in Refractory/Relapse Advanced Pediatric Solid Tumor: A Retrospective Study</p>

Activated Signaling Pathways and Targeted Therapies in Desmoid-Type Fibromatosis: A Literature Review

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