Elsevier

European Journal of Cancer

Volume 72, February 2017, Pages 192-199
European Journal of Cancer

Original Research
Quality of life and swallowing with standard chemoradiotherapy versus accelerated radiotherapy and panitumumab in locoregionally advanced carcinoma of the head and neck: A phase III randomised trial from the Canadian Cancer Trials Group (HN.6)

https://doi.org/10.1016/j.ejca.2016.11.008Get rights and content

Highlights

  • Three hundred twenty head and neck cancer patients participated in a phase III randomised trial comparing standard radiotherapy /cisplatin with accelerated radiotherapy/panitumumab.

  • Quality of life (QOL) and swallowing outcomes were compared between arms.

  • No clinically important differences by arm were seen 2–36 months post-treatment.

  • Swallowing and head and neck–specific QOL showed persistent declines in both study arms.

  • These results do not suggest adopting the experimental arm to improve QOL.

Abstract

Aim

To compare quality of life (QOL) between standard (SFX) chemoradiotherapy (arm A) and altered fractionation radiotherapy (AFX) with panitumumab (PMab; arm B).

Methods

Patients with T any N + M0 or T3-4N0M0 squamous cell head-neck carcinoma were randomised to SFX (70 Gy/35/7 wks) plus cisplatin (100 mg/m2 IV × 3) versus AFX (70 Gy/35/6 wks) plus PMab (9 mg/kg IV × 3). QOL was collected at baseline, end of radiation therapy (RT) and 2, 4, 6, 12, 24 and 36 months post-RT using the Functional Assessment of Cancer Therapy Head and Neck (FACT-H&N), MD Anderson Dysphagia Index (MDADI) and SWAL-QOL. We hypothesised a 6-point more favourable change in FACT-H&N score from baseline to 1 year in arm B over arm A.

Results

Among 320 patients, median follow-up was 46 (range: 0.1–64.3) months, median age 56, 84% male, Eastern Cooperative Oncology Group PS 0 (71%), 1 (29%). Primary site was oropharynx in 81% (p16+ 68%, p16− 16%, missing 16%). Baseline scores did not differ by arm (A/B): FACT-H&N 116.5/115, MDADI Global 83/77, SWAL-QOL General 67/68. At 1 year, no difference was seen between arms in FACT-H&N change from baseline: A −1.70, B −4.81, p = 0.194. Subscale change scores by arm were (A/B): last week RT, FACT-Physical (−11.6, −10, p = 0.049), MDADI Physical (−40.4, −33.9, p = 0.045), and SWAL-QOL Eating Duration (−61.2, −51.2, p = 0.02), Eating Desire (−53.3, −43.9, p = 0.031) and Mental Health (−42, −32.6, p = 0.009); 4 months, HN subscale (−7.7, −10, p = 0.014). No clinically important differences by arm were seen post-treatment.

Conclusions

PMab with AFX did not durably improve QOL or swallowing as compared with SFX with cisplatin.

Trial registration

ClinicalTrials.gov: NCT00820248.

Introduction

Disease control for locoregionally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) is improving, particularly in human papillomavirus (HPV)–related oropharyngeal cancers (OPC). Accepted treatment strategies produce significant long-term functional impact [1]. Current trials focus on developing equi-effective approaches with improved function relative to the standard, concurrent cisplatin with radiation therapy (RT) [2], [3], [4], [5], [6], [7].

Improvements in survival for LA-SCCHN by the addition of chemotherapy or accelerated fractionation are at the expense of quality of life (QOL) [8]. Although studied with increasing frequency [9], QOL has been reported in few head and neck cancer randomised trials. The QOL effect of combining the epidermal growth factor receptor–inhibitor panitumumab (PMab) with accelerated fractionation RT (AFX) is unknown.

Concomitant epidermal growth factor receptor–inhibitor cetuximab, with RT, compared with RT alone, improved survival without worsening QOL in LA-SCCHN in the IMCL-9815 study [10], [11]. Consequently, the HN.6 randomised phase III trial comparing progression-free survival (PFS) in patients with LA-SCCHN treated with standard fractionation (SFX) plus high-dose cisplatin (CIS) versus AFX plus PMab was designed with multiple secondary patient-reported outcomes (PROs). The standard arm was based on the Radiation Therapy Oncology Group 0129 trial, which showed no statistically significant difference in efficacy, acute or late toxicity, between 3 cycles of high-dose CIS with SFX versus 2 cycles with AFX. Since subgroup analysis of the IMCL-9815 study favoured AFX with biotherapy, AFX was chosen for the experimental arm.

PROs were measured as secondary end-points, however with a per-protocol primary QOL hypothesis: the median change in overall FACT-H&N score from baseline to 1 year would be 6 units higher in arm B (PMab/AFX) as compared with arm A (CIS/SFX). Although a previous study of AFX alone showed a median improvement of 8 units over 1 year, with systemic therapy in both arms, it was anticipated that overall QOL may decrease from baseline [12].

Section snippets

Patients and methods

Details of the HN.6 design and efficacy analysis have been published [13]. In brief, this multi-centre, open-label, randomised-controlled phase III Canadian Cancer Trials Group (CCTG) trial accrued fit patients with LA-SCCHN of the oral cavity, oropharynx, larynx or hypopharynx defined as T (any), N+, M0 or T3-4, N0, M0.

From December 2008 to November 2011, eligible patients stratified by T-category and N-category, intensity-modulated RT versus 3-dimensional conformal RT and anatomic location

Results

Among 320 patients randomised, one in arm A and two in arm B were ineligible for PROs due to language. At baseline, 313 patients (157/159 on arm A and 156/158 on arm B) reported FACT-H&N (98.7% compliance). Patients in both arms had similar baseline characteristics and PRO scores (Table 1). The median follow-up was 46 (0.1–64.3) months, with data cut-off by October 31, 2014. Compliance is shown in eTable 1 (Supplement). At 1 year, 262 (126 arm A, 136 arm B) patients remained available for QOL

Discussion

We failed to detect any durable QOL benefit of substituting PMab/AFX for standard, high dose CIS/SFX. A transient benefit in the last week of therapy in a few domains was not sustained; only SWAL-QOL eating duration met the MID criteria. In the context of no demonstrated PFS or toxicity benefit, our results do not support adopting a new strategy.

Limitations in the study overall have been discussed elsewhere [13]. With regard to the QOL and swallowing outcomes, the high proportion of

Funding sources

Study conduct of HN.6 was supported by Amgen Inc. and by the Canadian Cancer Society Research Institute (CCSRI grant number: 021039). Panitumumab on this study was supplied by Amgen Inc. The Canadian Cancer Trials Group, Kingston, ON, Canada had full access to all the data in the study. Both Drs. Wendy Parulekar and Dr. Bingshu Chen had full access to all of the data in the study; Dr. Parulekar takes responsibility for the integrity of the data and Dr. Chen for the accuracy of the data

Conflict of interest statement

None declared.

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