Pazopanib or methotrexate–vinblastine combination chemotherapy in adult patients with progressive desmoid tumours (DESMOPAZ): a non-comparative, randomised, open-label, multicentre, phase 2 study

Toulmonde, Maud; Pulido, Marina; Ray‐Coquard, Isabelle; Thewis, André; Isambert, Nicolás; Chevreau, Christine; Penel, Nicolas; Bompas, Emmanuelle; Saâda, Esma; Bertucci, François; Lebbe, Célèste; Cesne, Axel Le; Soulié, P; Piperno‐Neumann, Sophie; Sweet, Stephen E.; Cecchi, Fabiola; Hembrough, Todd; Bellera, C.; Kind, Michèle; Crombé, Amandine; Lucchesi, Carlo; Loarer, François Le; Blay, Jean‐Yves; Italiano, Antoîne

doi:10.1016/s1470-2045(19)30276-1

Cited by 147 publications

(127 citation statements)

References 31 publications

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“…Recently, novel medical therapies such as tyrosine kinase inhibitors or gamma-secretase inhibitors have shown promising activity in DTs 21–24. Also, in clinical trials, the number of patients with FAP-associated DT included has been very low, consistent with epidemiological expectations.…”

Section: Discussionmentioning

confidence: 62%

“…For example, the promising gamma-secretase inhibitor nirogacestat was evaluated in a phase II trial in 17 patients with DT, of which only 3 (17.6%) had FAP-associated DTs 23. Similarly, in the recent phase II evaluating pazopanib or low-dose MTX+vinblastine activity in progressive DTs, out of 72 patients recruited, only 8 (11.1%) had confirmed APC mutations; the PFS rate at 6 months in the overall group was only 45% 21. An effort to better understand the role of these therapies in FAP-related DTs should be advocated.…”

Section: Discussionmentioning

confidence: 99%

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Familial adenomatosis polyposis–related desmoid tumours treated with low-dose chemotherapy: results from an international, multi-institutional, retrospective analysis

et al. 2020

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IntroductionDesmoid tumour (DT) is a locally aggressive fibroblastic proliferative disease representing the most common extraintestinal manifestation of familial adenomatosis polyposis (FAP). As data on the activity of chemotherapy in these patients are limited, we examined the outcomes of patients treated with low-dose methotrexate (MTX)+vinca alkaloids (vinorelbine or vinblastine).Patients and methodsWe retrospectively reviewed clinical and outcome data from all patients with confirmed FAP-associated DTs treated with weekly MTX+vinca alkaloids in seven European sarcoma reference centres between January 2000 and December 2018. Radiological responses were assessed using RECIST V.1.0 and V.1.1. The Kaplan-Meier method associated to the log-rank test was used to estimate and compare survival curves.ResultsWe identified 37 patients (median age 29 years, range 7–44). According to RECIST, 20/37 (54.1%) patients achieved partial response (PR), 15/37 (40.5%) patients had stable disease and 2/37 (5.4%) had progressive disease as best response. Overall, the median progression-free survival (PFS) was 6.5 years (range, 0.3–12.1 years). In the subset of patients achieving PR as best response, the median PFS was not reached. In a subset of 11 patients with progressive disease offered MTX+vinca alkaloids rechallenge (after chemotherapy withdrawal following prolonged disease control), the disease control rate was 100%, resulting in a median PFS after rechallenge of 5.8 years.ConclusionsThis is the largest series on the activity of low-dose chemotherapy in patients with FAP-related DT. In this population, MTX+vinca alkaloids is an active combination, as already reported in patients with sporadic DT.

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Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Familial adenomatosis polyposis–related desmoid tumours treated with low-dose chemotherapy: results from an international, multi-institutional, retrospective analysis

et al. 2020

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“…Methotrexate (MTX) and vinblastine (VBL) chemotherapy is an effective treatment for DF. Most of the past studies using MTX + VBL for DF have adopted a weekly regimen, and major side effects have been reported 10‐13 …”

Section: Introductionmentioning

confidence: 99%

Desmoid with biweekly methotrexate and vinblastine shows similar effects to weekly administration: A phase II clinical trial

et al. 2020

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Low‐dose methotrexate (MTX) plus vinblastine (VBL) chemotherapy is an effective treatment for desmoid‐type fibromatosis (DF). However, previous reports have described a weekly regimen, with no reports available on a biweekly one. The aim of this study was to determine the clinical outcomes of a biweekly regimen in a cohort prospectively treated in our single institution. Since 2010, we have prospectively treated refractory DF patients with biweekly MTX (30 mg/m2) + VBL (6 mg/m2). Efficacy, progression‐free survival (PFS), and correlating factors were analyzed. Adverse events (AEs) were recorded. In total, 38 patients received low‐dose MTX + VBL therapy, and its efficacy was assessed in 37 of them. Nineteen (51%) patients showed partial response (PR). Clinical benefit rate was 95%. PFS at 5 y was 80.8%. In PR cases, median time to response was 10 mo. Longer duration of therapy was significantly associated with the response of PR (P = .007) by univariate analysis. There was no clear association between various clinicopathological factors, including tumor size, location, catenin beta‐1 (CTNNB1) mutation status with effect. Only 3 AEs of grade 3/4 were observed. Tumor regrowth after MTX + VBL discontinuation was observed in 5 (20%) of 25 patients. Biweekly administration of MTX + VBL chemotherapy was well tolerated compared with weekly administration, and its efficacy was anticipated in DF patents, although the time needed to achieve a response may be relatively long. The treatment interval should be determined taking into account both the condition of the tumor and the patient's preference.

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“…Targeted therapies with imatinib and sorafenib have also been investigated, but there is no randomized study showing their benefits. A recently published noncomparative, randomized, open-label, multicenter, phase 2 study (DESMOPAZ) demonstrated that pazopanib is a viable option for progressive desmoid tumors [27]. Regardless of the selected therapeutic strategy, the recurrence rate remains high -24 -77% [28].…”

Section: Resultsmentioning

confidence: 99%

Ruptured desmoid tumor imitating acute appendicitis – a rare reason for an emergency surgery

et al. 2019

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Background: Desmoid tumors, also known as aggressive fibromatosis, are extremely rare, accounting for less than 3% of soft-tissue sarcomas and less than 0,03% of all neoplasms. The diagnosis is usually delayed because of the lack of specific symptoms, and can sometimes lead to serious and, even fatal complications. Case presentation: We report the case of a 27-year-old male patient presenting with the clinical picture of acute appendicitis. During the operation, we found a tumor in the jejunum with a necrotic zone and perforation on its surface, causing hemorrhagic effusion into the abdominal cavity and subsequent peritonitis. The tumor was removed with negative margins via resection of the small bowel. The final histological result showed aggressive fibromatosis. Conclusions: Aggressive fibromatosis remains a serious problem with the possibility of locally aggressive behavior with high rates of recurrence. Sometimes, its clinical and macroscopic recognition can be immensely tricky. As shown by our patient, on rare occasions, desmoid tumors can lead to acute surgical abdomen requiring an emergency operation.

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Pazopanib or methotrexate–vinblastine combination chemotherapy in adult patients with progressive desmoid tumours (DESMOPAZ): a non-comparative, randomised, open-label, multicentre, phase 2 study

Cited by 147 publications

References 31 publications

Familial adenomatosis polyposis–related desmoid tumours treated with low-dose chemotherapy: results from an international, multi-institutional, retrospective analysis

Familial adenomatosis polyposis–related desmoid tumours treated with low-dose chemotherapy: results from an international, multi-institutional, retrospective analysis

Desmoid with biweekly methotrexate and vinblastine shows similar effects to weekly administration: A phase II clinical trial

Ruptured desmoid tumor imitating acute appendicitis – a rare reason for an emergency surgery

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