Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial

Graaf, Winette T.A. van der; Blay, Jean‐Yves; Chawla, Sant P.; Kim, Dong Wan; Bui-Nguyen, B.; Casali, Paolo G.; Schöffski, Patrick; Aglietta, Massimo; Staddon, Arthur P.; Beppu, Yasuo; Cesne, Axel Le; Gelderblom, Hans; Judson, Ian; Araki, Nobuhito; Ouali, M.; Marréaud, Sandrine; Hodge, Rachel; Dewji, M.R.; Coens, Corneel; Demetri, George D.; Fletcher, Christopher D.�M.; Tos, Angelo Paolo Dei; Hohenberger, Peter

doi:10.1016/s0140-6736(12)60651-5

Cited by 1,833 publications

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“…Pazopanib is an orally available, multitarget tyrosine kinase inhibitor with activity against vascular endothelial growth factor receptor 1 (VEGFR‐1), VEGFR‐2, and VEGFR‐3 and against platelet‐derived growth factor receptor α (PDGFR‐α), PDGFR‐α, and c‐kit 7. The European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group (STBSG), in collaboration with GlaxoSmithKline (GSK), carried out a phase 3 study (pazopanib for metastatic soft‐tissue sarcoma [PALETTE]) to evaluate the efficacy of pazopanib in patients with STS 8. Three hundred sixty‐nine patients were randomized (2:1) to pazopanib or placebo.…”

Section: Introductionmentioning

confidence: 99%

“…A significant 3‐month advantage in progression‐free survival (PFS) was observed in the pazopanib arm; however, it should be noted that patients who had liposarcoma (LPS) or some other types of STS were excluded from enrollment 8. LPS was excluded based on results from a phase 2 trial that did not demonstrate a sufficient benefit from pazopanib treatment in patients with LPS 9.…”

Section: Introductionmentioning

confidence: 99%

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The clinical outcome of pazopanib treatment in Japanese patients with relapsed soft tissue sarcoma: A Japanese Musculoskeletal Oncology Group (JMOG) study

Nakamura

Matsumine

Kawai

et al. 2016

Cancer

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113

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BACKGROUNDBecause the efficacy and safety of pazopanib in Japanese patients with soft tissue sarcoma (STS) had not been evaluated previously in a large‐scale cohort, the authors investigated the efficacy and safety of pazopanib in 156 Japanese patients with relapsed STS. This was a retrospective study based on the collection of real‐life, postmarketing surveillance data.METHODSPatients received pazopanib with the objective of treating local recurrence (n = 20), metastasis (n = 104), and both (n = 32). The patient median age was 53.8 years. The primary objective of this study was to clarify the efficacy of pazopanib for patients with STS.RESULTSThe median treatment duration was 28.7 weeks, and the average dose intensity of pazopanib was 609 mg. Adverse events occurred in 127 patients (81.4%). In addition to the main common toxicities, such as hypertension and liver disorder, pneumothorax (n = 11) and thrombocytopenia (n = 16) also were observed. The median progression‐free survival for all patients was 15.4 weeks. The median progression‐free survival for patients with leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma, and liposarcoma was 18.6 weeks, 16.4 weeks, 15.3 weeks, and 8 weeks, respectively. The median survival for all patients was 11.2 months. The median survival for patients with leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma, and liposarcoma was 20.1 months, 10.6 months, 9.5 months, and 7.3 months, respectively.CONCLUSIONSThere were apparent differences in the efficacy of pazopanib treatment among histologic types of STS. Pazopanib treatment is a new treatment option; however, adverse events like pneumothorax and thrombocytopenia, which did not occur frequently in the PALETTE study (pazopanib for metastatic soft‐tissue sarcoma), should be taken into consideration. Cancer 2016;122:1408‐16. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The clinical outcome of pazopanib treatment in Japanese patients with relapsed soft tissue sarcoma: A Japanese Musculoskeletal Oncology Group (JMOG) study

Nakamura

Matsumine

Kawai

et al. 2016

Cancer

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113

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“…In general, the health‐related quality of life declined over time over a similar range in both arms. Pazopanib was associated with a significant detrimental impact on the quality of life because of diarrhea, anorexia, nausea/vomiting, and asthenia 7, 11. Pazopanib treatment did not significantly reduce the symptom burden.…”

Section: Discussionmentioning

confidence: 94%

“…This justifies early supportive/palliative‐care interventions. The data assessing the quality of life of patients with advanced STS are sparse 5, 6, 7, 8, 11. The evidence demonstrating that systemic treatment decreases the symptom burden in patients with advanced sarcoma is missing.…”

Section: Discussionmentioning

confidence: 99%

“…The evidence demonstrating that systemic treatment decreases the symptom burden in patients with advanced sarcoma is missing. In the Pazopanib Explored in Soft Tissue Sarcoma (PALETTE) trial (pazopanib vs placebo), quality of life was assessed with a validated health‐related self‐questionnaire such as the Quality of Life Questionnaire Core 30 7, 11. In general, the health‐related quality of life declined over time over a similar range in both arms.…”

Section: Discussionmentioning

confidence: 99%

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REGOSARC: Regorafenib versus placebo in doxorubicin‐refractory soft‐tissue sarcoma—A quality‐adjusted time without symptoms of progression or toxicity analysis

Berry

Basson

Bogart

et al. 2017

Cancer

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BACKGROUNDIn a placebo‐controlled, randomized phase 2 trial (ClinicalTrials.gov identifier NCT01900743), regorafenib improved progression‐free survival (PFS) for patients with doxorubicin‐pretreated advanced nonadipocytic sarcoma. A quality‐adjusted time without symptoms of progression or toxicity (Q‐TWiST) post hoc exploratory analysis was applied to provide an integrated measure of its clinical benefit.METHODSIn the base‐case analysis, each patient's overall survival (OS) was partitioned into 3 mutually exclusive health states: the time with a grade 3 or 4 adverse event (TOX), the time without symptoms of disease or grade 3 or 4 toxicity from treatment, and the time after tumor progression or relapse. The time spent in each state was weighted with a health‐state utility associated with that state and was summed to calculate the Q‐TWiST. The stability of the base‐case analysis was explored with several sensitivity analyses.RESULTSIn nonadipocytic sarcoma, the PFS was (4.0 months [2.6‐5.5 months] with regorafenib vs 1.0 month [0.9‐1.8 months] with a placebo; hazard ratio, 0.36 [0.25‐0.53]; P < .0001); the OS was 13.4 months (8.6‐17.3 months) with regorafenib and 9.0 months (6.8‐12.5 months) with a placebo (hazard ratio, 0.67 [0.44‐1.02]). With the classic definition of TOX (including all grade 3 and 4 clinical adverse events), the Q‐TWiSTs were 8.0 months (7.0‐9.0 months) with regorafenib and 5.7 months (4.9‐6.4 months) with a placebo (P < .001).CONCLUSIONSFor patients with doxorubicin‐pretreated soft‐tissue sarcoma, regorafenib significantly improved quality‐adjusted survival in comparison with a placebo. Cancer 2017;123:2294–2302. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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Implementation of Genetic Screening to Prevent Severe Cutaneous Adverse Drug Reactions Is Crucial—Rebuttal From the Devil’s Antagonist—Reply

Divito

2020

JAMA Dermatol

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treatments. 2 In contrast to systemic symptoms, this subset of patients with dermatomyositis is characterized by milder inflammatory cutaneous manifestations, usually associated with calcinosis cutis and peripheral edema. Skin disease remission is easier to achieve in these patients 2 compared with those who have long-standing systemic symptoms.In this observation, we describe a rare case of dermatomyositis with Degos-like skin lesions. To our knowledge, the literature contains few other reports of analogous cutaneous manifestations in connective tissue diseases, including dermatomyositis, systemic lupus erythematosus, and systemic sclerosis. 3,4 This case report describes a specific manifestation of dermatomyositis and a phenotypic overlap: both a Degos disease-like presentation and NXP-2 antibodies are indicative of vascular injury with involvement of the gastrointestinal tract. 5,6 Therefore, this case report stimulates future speculation about the interplay between inflammation and autoimmunity, which could translate into a new skin phenotype.

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Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial

Cited by 1,833 publications

References 31 publications

The clinical outcome of pazopanib treatment in Japanese patients with relapsed soft tissue sarcoma: A Japanese Musculoskeletal Oncology Group (JMOG) study

The clinical outcome of pazopanib treatment in Japanese patients with relapsed soft tissue sarcoma: A Japanese Musculoskeletal Oncology Group (JMOG) study

REGOSARC: Regorafenib versus placebo in doxorubicin‐refractory soft‐tissue sarcoma—A quality‐adjusted time without symptoms of progression or toxicity analysis

Implementation of Genetic Screening to Prevent Severe Cutaneous Adverse Drug Reactions Is Crucial—Rebuttal From the Devil’s Antagonist—Reply

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