Phase II study of panitumumab and paclitaxel as first-line treatment in recurrent or metastatic head and neck cancer. TTCC-2009-03/VECTITAX study
Introduction
Patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) are exposed to a significant risk of relapse. Indeed, over 50% of the patients treated with a curative intent will experience a recurrence (locoregional or distant), and 10% of the patients are metastatic at diagnosis [1]. Until recently, combination of cisplatin-fluorouracil was the standard of care [2]. A modest initial improvement was achieved with the addition of taxanes [3]. However, no further benefit has been observed with the combinations of platinum and taxanes in the last 10 years, suggesting that an efficacy plateau has been reached [4].
The EGFR pathway is commonly activated in SCCHN [5], [6] triggering a membrane-to-nucleus signaling pathway [7] which stimulates growth and mitosis and also inhibits apoptosis. The combination of cetuximab, a chimeric IgG1 anti-EGFR monoclonal antibody, with cisplatin-fluorouracil results in improved outcomes when used for treating patients with relapsed or metastatic SCCHN as compared with cisplatin-fluorouracil, providing about 10 months overall survival (OS) [8]. This regimen is the standard of care for fit patients able to receive cisplatin. However, prognosis of these patients still remains poor and therefore, new options are needed. Moreover, cisplatin requires patients to be fit and alternatives without cisplatin may have a role in the treatment of patients with poor performance status and nutritional issues.
Panitumumab, a fully human IgG2 anti-EGFR monoclonal antibody, has shown activity in preclinical models of SCCHN [9], and promising activity in refractory SCCHN patients in a phase I clinical trial [10]. Recently, our cooperative group also reported encouraging outcomes of anti-EGFR-paclitaxel combination in a phase II study [11]. On the basis of this background, a phase II clinical trial (VECTITAX study) was designed with the objective of evaluating the activity and safety profile of panitumumab in combination with paclitaxel in patients with recurrent or metastatic SCCHN.
Section snippets
Materials and methods
The VECTITAX study was a single arm, open label, multicenter, phase II clinical trial. To be included patients had to have histologically or cytologically confirmed SCCHN. The current situation had to be recurrent or metastatic, deemed to be untreatable by surgery or radiotherapy. No previous systemic antineoplastic therapy for the recurrent/metastatic disease may have been administered. However, previous chemotherapy was allowed as a part of a multimodality radical treatment if completed > 24
Baseline characteristics
Between March 2011 and May 2012, 40 patients were included in 12 centers in Spain (ITT population). One patient met two exclusion criteria (second active neoplasm and B-Hepatitis) and four lacked post-baseline response assessment. Therefore, the PP population comprised 35 patients. Table 1 shows the baseline characteristics for the ITT population. Median age was 61 [range = 43–83] and 35 patients (87%) were male. Main tumor sites were larynx (N = 14; 35%) and oropharynx (N = 12; 30%). Previous
Discussion
Results of this study show that panitumumab and paclitaxel in combination were effective and well tolerated, resulting in almost 50% of confirmed ORR, a median OS close to 10 months and a median PFS of 7.5 months when used upfront to treat patients with relapsed or metastatic SCCHN.
First-line combination of anti-EGFR with taxane in a non-platinum regimen has been previously investigated. Our cooperative group published in 2012 the results of a phase II study [11] on cetuximab-paclitaxel (ERBITAX)
Conflict of interest
Ricard Mesia has received lecturer fees from Merck Serono and has received consultant or advisor fees from Merck Serono and Innate pharma. Juan Carlos Adansa Klain has received research fundings from Pfizer S.L.U., and has received support for travel, accommodations, meeting expenses to 18th ECCO - 40th ESMO from AMGEN S.A. Juan Jesús Cruz Hernández has received lecturer fees from Celgene, EISAI Farmacéutica S.A., TEVA S.A., Roche Farma S.A., Pfizer S.L.U. and has received consultant or advisor
Acknowledgements
The authors thank the 40 patients who consented to participate in this study, and all their colleagues who have participated in this study and are not included in the list of authors, in alphabetical order: C. García-Girón (Hospital General Yagüe, Burgos), J.A. García Sáenz (Hospital Clínico San Carlos, Madrid), J.J. Grau (Hospital Clinic i Provincial, Barcelona), A. Hurtado (Hospital Universitario Fundación Alcorcón, Madrid), A. López-Pousa (Hospital Santa Creu i Sant Pau, Barcelona).
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