A Rationale for the Activity of Bone Target Therapy and Tyrosine Kinase Inhibitor Combination in Giant Cell Tumor of Bone and Desmoplastic Fibroma: Translational Evidences

Vita, Alessandro De; Vanni, Silvia; Miserocchi, Giacomo; Fausti, Valentina; Pieri, Federica; Spadazzi, Chiara; Cocchi, Claudia; Liverani, Chiara; Calabrese, Chiara; Casadei, Roberto; Recine, Federica; Gurrieri, Lorena; Bongiovanni, Alberto; Ibrahim, Toni; Mercatali, Laura

doi:10.3390/biomedicines10020372

Cited by 34 publications

(27 citation statements)

References 47 publications

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“…Antibody-drug conjugate (ADC) drugs against NY-ESO-1 have already demonstrated evidence of activity. 38 Additionally, some new biomarkers such as neurotrophic tyrosine receptor kinase (NTRK), 11 RANK-L, 12 and corresponding drugs larotrectinib, denosumab have also been shown to affect certain sarcomas dramatically.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Efficacy and Safety of Anlotinib as a Monotherapy and Combined Therapy for Advanced Sarcoma

Yao¹,

Du²,

Wang³

et al. 2022

OTT

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Objective To analyze the effectiveness of the long-term (> 12 months) administration of anlotinib as a monotherapy or combined therapy in patients with advanced sarcomas. Methods A retrospective analysis was conducted of patients with advanced sarcomas with measurable target lesions since 2018. Twenty-two of the patients had taken anlotinib regularly for > 12 months. The patients’ general information and the drug’s clinical efficacy and toxicity data were collected and statistically analyzed using RECIST 1.1 to measure the target lesions and tumor PFS time as the main endpoints. We used a swimmer plot to observe the drug’s efficacy and duration, and employed a waterfall plot to express the best treatment effect. Results The study included 14 male and 8 female patients, ranging in age from 14 to 75 (mean: 44.82) years. The primary diseases included alveolar soft part sarcoma, synovial sarcoma, leiomyosarcoma, and others. The metastasis sites were the lungs in fifteen cases, lymph nodes in four cases, and multiple sites in three cases. Fourteen patients had previously undergone chemotherapy. The current therapy protocol was oral anlotinib alone for nine cases, combination chemotherapy for nine cases, and combination immunotherapy (anti-PD-1) for four cases. The highest clinical efficacy was complete remission (CR) in four (18.18%) cases, partial response (PR) in five (22.73%) cases, and stable disease in 13 (59.09%) cases, with an odds ratio of response of 40.91%. The mean PFS for the CR, PR, and stable disease groups was 16.50, 14.50, and 29.31 months, respectively (p < 0.05). The main adverse effects included hand-foot syndrome, hypertension, and leukopenia. Conclusion Anlotinib monotherapy or combination therapy can be more effective and safer for certain advanced sarcomas, with more extended maintenance and acceptable side effects. Clinical efficacy at the CR and PR levels might predict the long-term PFS in certain advanced sarcomas.

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Section: Discussionmentioning

confidence: 99%

Long-Term Efficacy and Safety of Anlotinib as a Monotherapy and Combined Therapy for Advanced Sarcoma

Yao¹,

Du²,

Wang³

et al. 2022

OTT

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“…Furthermore, literature data suggest that genes involved in bone vascular formation, such as OPG and VEGF seem to have a potential role as new antiangiogenic generation drugs, including the multitarget tyrosine-kinase inhibitor lenvatinib. Interestingly, the combination of denosumab and lenvatinib seems to be a promising therapeutic strategy in GCTB [ 20 , 21 ].…”

Section: Discussionmentioning

confidence: 99%

Bone Turnover Marker (BTM) Changes after Denosumab in Giant Cell Tumors of Bone (GCTB): A Phase II Trial Correlative Study

Palmerini

Pazzaglia

Cevolani

et al. 2022

Cancers

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Background: Giant cell tumors of bone (GCTB) are osteolytic tumors. Denosumab, a RANK-L inhibitor, is approved for GCTB. Data on serum bone turnover marker (sBTM) changes are lacking. We present a phase II correlative study on sBTMs in GCTB patients treated with denosumab. Methods: All GCTB patients receiving denosumab within a multicentre, open-label, phase 2 study were enrolled. Serum levels of carboxyterminal-crosslinked-telopeptide of type I collagen (s-CTX), alkaline phosphatase (ALP), bone-alkaline phosphatase (bALP), parathyroid hormone (sPTH), and osteocalcin (OCN) were prospectively assessed (baseline, T0, 3 months, T1, 6 months, T2). The primary endpoint was assessment of sBTM changes after denosumab; the secondary endpoints were disease-free survival (DFS) and sBTM correlation. Results: In 54 cases, sBTMs decreased during denosumab treatment except for sPTH. With a median follow-up of 59 months, 3-year DFS was 65% (%CI 52–79), with a significantly worse outcome for patients with high (≥500 UI/mL) s-CTX at baseline, as compared to low s-CTX (<500 UI/mL) (3-year DFS for high CTX 45% (95%CI 23–67) vs. 75% (95%CI 59–91) for low s-CTX. Higher median ALP and s-CTX were found for patients with tumor size ≥ 5 cm (p = 0.0512; p = 0.0589). Conclusion: Denosumab induces ALP/OCN and s-CTX reduction. High baseline s-CTX identifies a group of patients at higher risk of progression of the disease.

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“…In particular, the axis RANK/RANKL/OPG was significantly unbalanced towards the bone resorption activation, which is responsible for orchestrating the bone vicious cycle and the activation of osteoclastogenesis potential. Furthermore, in vitro and in vivo zebrafish analyses provided evidence for suggesting the combination of denosumab and multitarget TKI inhibitor lenvatinib as a promising therapeutic strategy in GCTB and DF compared to monoregimen chemotherapy ( 29 ). This report provided useful methods and ideas for the study of the molecular mechanism and potential therapeutic targets in adamantinoma.…”

Section: Discussionmentioning

confidence: 99%

Rapidly Progressive Classic Adamantinoma of the Spine: Case Report and Literature Review

Lou

Liu

et al. 2022

Front. Oncol.

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Adamantinoma is a locally aggressive or malignant tumor, accounting for <0.5% of all primary bone tumors. The tumor usually progresses slowly, with a relatively promising prognosis. Primary or metastatic spinal adamantinoma of bone are rarer. Only four cases have been documented till date. We present two cases of aggressive spinal adamantinoma whose microphotography and radiographic appearance were unusual, with extensive involvement of multiple segments and rapid progression. Case 1 was a 36-year-old woman, presenting with back pain, progressive numbness and motor weakness, who was diagnosed with metastatic adamantinoma in the T2, T7, L2, and L4. She underwent spondylectomy three times to resect these lesions, respectively. Case 2 was a 68-year-old male with complaints of severe left back pain. MRI revealed destructive changes in T1-T4. He underwent posterior decompression (T1-T3), partial vertebrectomy (T2), fixation and fusion (C5-C7, T4-T6). The pathology of two patients was metastatic spinal adamantinoma, whose primary lesions were from tibia and femoral adamantinoma, respectively. Rapid squamous progression was observed in specimens of T2 and T7 lesions of Case 1 in two months. Twenty-five months after surgery, Case 1 developed paralysis, but she refused to receive further examination and treatment. Two months after surgery, Case 2 presented with an upper back pain again. The MRI revealed an increase in osseous destruction and paravertebral mass size. He was administered radiotherapy, with his upper back pain partially relieved. The biological behavior of classic adamantinoma is highly unpredictable, often exhibiting more aggressive behavior upon recurrence or metastasis. The pathological diagnosis of adamantinoma should be confirmed by preoperative biopsy. En bloc resection with a wide margin is the preferred treatment for primary spinal adamantinoma. Radiation therapy can partially relieve the pain.

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A Rationale for the Activity of Bone Target Therapy and Tyrosine Kinase Inhibitor Combination in Giant Cell Tumor of Bone and Desmoplastic Fibroma: Translational Evidences

Cited by 34 publications

References 47 publications

Long-Term Efficacy and Safety of Anlotinib as a Monotherapy and Combined Therapy for Advanced Sarcoma

Long-Term Efficacy and Safety of Anlotinib as a Monotherapy and Combined Therapy for Advanced Sarcoma

Bone Turnover Marker (BTM) Changes after Denosumab in Giant Cell Tumors of Bone (GCTB): A Phase II Trial Correlative Study

Rapidly Progressive Classic Adamantinoma of the Spine: Case Report and Literature Review

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