Elsevier

Oral Oncology

Volume 75, December 2017, Pages 54-60
Oral Oncology

Results of a phase II randomized controlled clinical trial comparing efficacy of Cabazitaxel versus Docetaxel as second line or above therapy in recurrent head and neck cancer

https://doi.org/10.1016/j.oraloncology.2017.10.018Get rights and content

Highlights

  • Cabazitaxel was compared with Docetaxel post first-line palliative chemotherapy.

  • Cabazitaxel failed to improve outcomes.

  • Docetaxel had a better disease control rate.

  • PFS and OS were also numerical superior with Docetaxel.

Abstract

Background

Cabazitaxel has shown activity in squamous cancer cell lines and in taxane resistant cell lines. Hence we planned a phase 2 study to evaluate the efficacy of cabazitaxel against Docetaxel in recurrent head and neck cancer, post first line treatment.

Methods

This was a phase 2, investigator initiated, randomized controlled trial of Docetaxel (75 mg/m2) versus Cabazitaxel (20 mg/m2), in patients with head and neck cancer with ECOG performance status 0–2 who have been exposed to at least one line of chemotherapy, involving a sample size of 92 (46 per group)(CTRI/2015/06/005848). Disease control rate at 6 weeks was assessed and compared using the chi-square test.

Results

The disease control rate at 6 weeks was better in the Docetaxel arm over the cabazitaxel arm (52.3% versus 13.6%, p = 0.017). The median progression free survival was 21 days (95% CI 5.28 to 36.72 days) in the cabazitaxel arm versus 61 days (95% CI 21.39 to 100.60 days) in the Docetaxel arm (HR-1.455, 95% CI 0.919–2.304, p = 0.100). The median overall survival was 115 days (95% CI 74.04 to 155.95 days) in the cabazitaxel arm versus 155 days (95% CI 148.6 to 161.40 days) in the Docetaxel arm (HR-1.464, 95% CI 0.849–2.523, p = 0.170).

Conclusion

Docetaxel had a superior disease control rate at 6 weeks compared to cabazitaxel.

Introduction

Head and neck squamous cell cancer (SCCHN) is the fifth most common cancer worldwide and is the most common neoplasm in central Asia [1]. Head and neck malignancies are common in regions of the world where tobacco use and alcohol consumption is high [2]. The five-year survival ranges from 20 to 90% depending upon the subsite of origin and the clinical extent of disease [3]. Current therapy consists of surgery, radiotherapy and chemotherapy [3]. More than 60% patients develop recurrence in locally advanced head and neck cancer [4]. The survival time of relapsed or metastatic squamous cell carcinoma of the head and neck (SCCHN) is less than one year [5], [6]. Cetuximab with Cisplatin and 5 FU is the current standard first line treatment [7]. However, until recently, there was no standard second line treatment although palliative chemotherapy has been widely used [5].

Taxanes are amongst the most widely used agents in the second line setting in head and neck cancer. Weekly schedule of Docetaxel is active and well tolerated as second line therapy in patients with metastatic/recurrent SCCHN with response rates ranging from 6 to 13% [8], [9]. Cabazitaxel has been found to be effective in metastatic castration-resistant prostate cancer patients who have failed with Docetaxel in the TROPIC study [10]. Similar findings were observed in a multicentric dose-escalating study of Cabazitaxel in combination with capecitabine in patients with metastatic breast cancer progressing after anthracycline and taxane treatment [11]. In head and neck cancer too, Cabazitaxel had shown activity in squamous cancer cell lines and taxane resistant cell lines [12], [13]. In a single arm phase 2 study of heavily pretreated recurrent head and neck cancer patients, it had shown a promising disease control rate of 27.6% [14]. Hence, we planned a randomized phase 2 study to evaluate the efficacy and safety of cabazitaxel against Docetaxel in recurrent head and neck cancer, after first line treatment.

Section snippets

Study design

This was an investigator initiated phase 2 open label, parallel group, controlled clinical trial of Docetaxel (75 mg/m2) versus Cabazitaxel (20 mg/m2), in patients with cancer of the head and neck, who have taken at least one line of chemotherapy. There was no amendment in the protocol after commencement of enrollment.

Participants

Adult recurrent locally advanced or metastatic head and neck cancer patients, with a life expectancy of 3 months or more, histological or cytological proof of squamous cell

Experimental arm

Cabazitaxel 20 mg/m2 given 3 weekly until progressive disease.

Standard arm

Docetaxel 75 mg/m2 given 3 weekly until progressive disease Pre-medication for Cabazitaxel and Docetaxel were mandatory and according to the manufacturer’s recommendations. Patients received dexamethasone (20 mg intravenous single dose) and promethazine (12.5 mg intravenous single dose) as premedication before both Cabazitaxel and Docetaxel. In addition dexamethasone (4 mg twice daily PO) was provided for 3 more days post

Baseline details

patients were accrued into the study, 46 in Cabazitaxel arm and 46 in Docetaxel arm, between October 2015 to January 2016. Consort diagram (See Fig. 1) provides the details of patients screened and selected for the study. The median age of the patients in study was 45 years (IQR{interquartile range} 38–55 years). The ECOG PS was 0–1 in 91 patients (98.9%) and 2 in 1 patient (1.1%). The site of malignancy was oral cavity in 72 patients (78.3%), oropharynx in 8 patients (8.7%), larynx in 3

Discussion

Ours is probably the first study in this setting which clearly demonstrates an improvement in outcome with Docetaxel over Cabazitaxel. The improvement in disease control at 6 weeks was doubled with Docetaxel than with Cabazitaxel. Further there was a trend towards improvement in PFS and OS with Docetaxel over Cabazitaxel. The results of another study comparing Cabazitaxel with methotrexate in second line setting in head and neck cancer were reported recently by Machiels et al. [17]. Cabazitaxel

Conclusion

In this phase 2 study, Docetaxel had a superior disease control rate at 6 weeks, PFS and OS when compared to cabazitaxel.

Acknowledgement

Sanofi. The study was funded by an unrestricted educational grant from Sanofi.

Conflict of interest

None.

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