Outcomes of Oral Vinorelbine in Progressive Desmoid Fibromatosis—Response
Authors: Olivier Mir, Charles Honoré, Ali N. Chamseddine, Matthieu Faron, Leila Haddag-Miliani, Arnaud Bayle, Axel Le Cesne
Journal: Clinical Cancer Research (2021)

We thank Zheng and colleagues for their interest in our article long-term outcomes of oral vinorelbine in advanced, progressive desmoid fibromatosis and influence of CTNNB1 mutational status (1). Their letter addresses relevant points concerning the use of a fixed dose of vinorelbine, and the limitations of RECIST in desmoid fibromatosis.Regarding treatment dosing, it should be kept in mind that the apparent clearance of oral vinorelbine is not related to body surface area (BSA; ref. 1).From a broader perspective, BSA-based dosing is associated with a significant reduction in interpatient pharmacokinetics variability in only approximately 15% of anticancer drugs (2). Alternative dosing strategies in this context include the use of fixed doses, with a possible input of mathematical modeling (3).Hence, the administration of fixed doses of oral vinorelbine is associated with limited pharmacokinetics variability (for doses below 120 mg; ref. 4), in contrast with BSA-based dosing schedules (5). Recent clinical data in desmoid fibromatosis also support the use of a fixed dose of 90 mg weekly (6), increasing the external validity of our findings.Whether intrapatient dose escalation would result in higher disease control rate is speculative. In contrast, it could theoretically result in more toxicity, and higher costs (related to drug supply and possibly increased toxicity). A prolonged duration of treatment would also result in higher maximal theoretical costs.Regarding tumor evaluation using RECIST 1.1, we agree with Zheng and colleagues on the limitations caused by unidimensional measurements. RECIST 1.1 also does not take into account signal changes on MRI.We believe that radiomic studies are clearly deserved in this setting, with a potential not only for early tumor evaluation while under systemic treatment (opening the gate for tailored treatment durations), but also as a potential prognostic factor at baseline.The nationwide study ALTITUDES conducted within the French Sarcoma Group (ClinicalTrials.gov ID: NCT02867033) was recently ended, after the enrollment of 630 patients. In addition to clinical data and analysis of the prognostic value of CTNNB1 mutations, radiomic approaches could be derived from this study.O. Mir reported personal fees from Amgen, Blueprint Medicines, Eli Lilly, Ipsen, Lundbeck, Pfizer, Roche, and Servier outside the submitted work. M. Faron reported personal fees from HRA Pharma and other from IPSEN and Novartis outside the submitted work. A. Bayle reported as part of the Drug Development Department (DITEP), principal/subinvestigator of clinical trials for AbbVie, Adaptimmune, Aduro Biotech, Agios Pharmaceuticals, Amgen, arGEN-X BVBA, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca Ab, Aveo, Basilea Pharmaceutica International Ltd, Bayer Healthcare Ag, BBB Technologies BV, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Ca, Celgene Corporation, Chugai Pharmaceutical Co, Clovis Oncology, Cullinan-Apollo, Daiichi Sankyo, Debiopharm, Eisai, Eisai Limited, Eli Lilly, Exelixis, Faron Pharmaceuticals Ltd, Forma Therapeutics, GamaMabs, Genentech, GlaxoSmithKline, H3 Biomedicine, Hoffmann La Roche Ag, ImCheck Therapeutics, Innate Pharma, Institut De Recherche Pierre Fabre, Iris Servier, Janssen Cilag, Janssen Research Foundation, Kura Oncology, Kyowa Kirin Pharm. Dev, Lilly France, Loxo Oncology, Lytix Biopharma As, Medimmune, Menarini Ricerche, Merck Sharp &amp; Dohme Chibret, Merrimack Pharmaceuticals, Merus, Millennium Pharmaceuticals, Molecular Partners Ag, Nanobiotix, Nektar Therapeutics, Novartis Pharma, Octimet Oncology Nv, Oncoethix, Oncopeptides, Orion Pharma, Ose Pharma, Pfizer, Pharma Mar, Pierre Fabre, Medicament, Roche, Sanofi Aventis, Seattle Genetics, Sotio A.S, Syros Pharmaceuticals, Taiho Pharma, Tesaro, and Xencor, research grants from AstraZeneca, BMS, Boehringer Ingelheim, Janssen Cilag, Merck, Novartis, Onxeo, Pfizer, Roche, and Sanofi, and nonfinancial support (drug supplied) from AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Medimmune, Merck, NH TherAguiX, Onxeo, Pfizer, and Roche. A. Le Cesne reported personal fees from PharmaMar and Bayer outside the submitted work. No disclosures were reported by the other authors.See the original Letter to the Editor, p. 2119