Randomized Phase II Study of Cabazitaxel Versus Methotrexate in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck Previously Treated With Platinum-Based Therapy.
Machiels, Jean-Pascal Henry; Van Maanen, Aline; Vandenbulcke, Jean-Marieet al.
[en] LESSONS LEARNED: Cabazitaxel has activity in squamous cell carcinoma of the head and neck (SCCHN) and taxane-resistant cell lines. For the first time, cabazitaxel was investigated in incurable patients with recurrent SCCHN. Patients were randomly assigned to cabazitaxel every 3 weeks or weekly methotrexate.This phase II study did not meet its primary endpoint.Cabazitaxel has low activity in SCCHN.The toxicity profile in this population also was not favorable owing to the high rate of febrile neutropenia observed (17%). BACKGROUND: Cabazitaxel is a second-generation taxane that improves the survival of patients with metastatic castrate-resistant prostate cancer following docetaxel therapy. Cabazitaxel has activity in squamous cell carcinoma of the head and neck (SCCHN) and taxane-resistant cell lines. In this randomized phase II trial, we investigated cabazitaxel in patients with recurrent SCCHN. METHODS: Patients with incurable SCCHN with progression after platinum-based therapy were randomly assigned to cabazitaxel every 3 weeks (cycle 1, 20 mg/m2, increased to 25 mg/m2 for subsequent cycles in the absence of nonhematological adverse events [AEs] greater than grade 2 and hematological AEs greater than grade 3) or methotrexate (40 mg/m2/week). The patients were stratified according to their performance status and previous platinum-based chemotherapy for palliation versus curative intent. The primary endpoint was the progression-free survival rate (PFSR) at 18 weeks. RESULTS: Of the 101 patients, 53 and 48, with a median age of 58.0 years (range, 41-80), were randomly assigned to cabazitaxel or methotrexate, respectively. The PFSR at 18 weeks was 13.2% (95% confidence interval [CI], 5%-25%) for cabazitaxel and 8.3% (95% CI, 2%-20%) for methotrexate. The median progression-free survival was 1.9 months in both arms. The median overall survival was 5.0 and 3.6 months for cabazitaxel and methotrexate, respectively. More patients experienced serious adverse events with cabazitaxel than with methotrexate (54% vs. 36%). The most common drug-related grade 3-4 AE in the cabazitaxel arm was febrile neutropenia (17.3%). CONCLUSION: This study did not meet its primary endpoint. Cabazitaxel has low activity in recurrent SCCHN.
Disciplines :
Oncology
Author, co-author :
Machiels, Jean-Pascal Henry
Van Maanen, Aline
Vandenbulcke, Jean-Marie
Filleul, Bertrand
Seront, Emmanuel
Henry, Stephanie
D'Hondt, Lionel
Lonchay, Christophe
Holbrechts, Stephane
Boegner, Petra
Brohee, Dany
Dequanter, Didier
Louviaux, Ingrid
Sautois, Brieuc ; Université de Liège > Département des sciences cliniques > Département des sciences cliniques
Randomized Phase II Study of Cabazitaxel Versus Methotrexate in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck Previously Treated With Platinum-Based Therapy.
Publication date :
2016
Journal title :
Oncologist
ISSN :
1083-7159
eISSN :
1549-490X
Publisher :
AlphaMed Press, United States - Ohio
Volume :
21
Pages :
1-10
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
(c)AlphaMed Press; the data published online to support this summary is the property of the authors.
Vermorken JB, Herbst RS, Leon X et al. Overview of the efficacy of cetuximab in recurrent and/or metastatic squamous cell carcinoma of the head and neck in patients who previously failed platinum based therapies. Cancer 2008;112:2710-2719.
Machiels JP, Haddad RI, Fayette J et al. Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): An open-label, randomised phase 3 trial. Lancet Oncol 2015;16:583-594.
Machiels JP, Subramanian S, Ruzsa A et al. Zalutumumab plus best supportive care versus best supportive care alone in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after failure of platinum-based chemotherapy: Anopen-label, randomisedphase3trial. Lancet Oncol 2011;12:333-343.
Stewart JS, Cohen EE, Licitra L et al. Phase III study of gefitinib compared with intravenous methotrexate for recurrent squamous cell carcinoma of the head and neck. J Clin Oncol 2009;27: 1864-1871 [corrected].
Machiels JP, Henry S, Zanetta S et al. Phase II study of sunitinib in recurrent or metastatic squamous cell carcinoma of the head and neck: GORTEC 2006-01. J Clin Oncol 2010;28:21-28.
Fayette J, Guigay J, Letourneau C et al. Cabazitaxel in patients with refractory recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): Final results of phase II trial UNICANCER ORL03. Eur J Cancer 2015;51:s557 [Abstract 2800].
Colevas AD. Chemotherapy options for patients with metastatic or recurrent squamous cell carcinoma of the head and neck. J Clin Oncol 2006;24:2644-2652.
Forastiere AA, Shank D, Neuberg D et al. Final report of a phase II evaluation of paclitaxel in patients with advanced squamous cell carcinoma of the head and neck: An Eastern Cooperative Oncology Group trial (PA390). Cancer 1998;82:2270-2274.
Dreyfuss AI, Clark JR, Norris CM et al. Docetaxel: An active drug for squamous cell carcinoma of the head and neck. J Clin Oncol 1996;14: 1672-1678.
Catimel G, Verweij J, Mattijssen V et al. Docetaxel (Taxotere): An active drug for the treatment of patients with advanced squamous cell carcinoma of the head and neck. EORTC Early Clinical Trials Group. Ann Oncol 1994;5:533-537.
de Bono JS, Oudard S, Ozguroglu M et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: A randomised open-label trial. Lancet 2010;376:1147-1154.
Mita AC, Denis LJ, Rowinsky EK et al. Phase I and pharmacokinetic study of XRP6258 (RPR 116258A), a novel taxane, administered as a 1- hour infusion every 3 weeks in patients with advanced solid tumors. Clin Cancer Res 2009;15: 723-730.
Diéras V, Lortholary A, Laurence V et al. Cabazitaxel in patients with advanced solid tumours: Results of a phase I and pharmacokinetic study. Eur J Cancer 2013;49:25-34.