Original ResearchQuality 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)
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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2023, International Journal of Radiation Oncology Biology PhysicsCitation Excerpt :Global HRQL (FACT-HN total) showed the typical U-shaped trajectory observed in other prospective CRT series, showing almost full recovery to their pretreatment (but post diagnosis) baseline reports (mean scores) in both groups by 6 months and demonstrating results at least similar to other contemporary HPVOPC trials.3 Although the long-term FACT-H&N total scores are higher than reported in either the CCTG HN.6 study or the TROG02.02 study, the baseline evaluations were lower in both of those studies, and all studies showed the typical recovery back to their reported pretreatment scores.41,42 The HADS anxiety and depression subscales also showed excellent results beyond the acute treatment period, with few patients meeting the screening threshold for emotional distress.
Patient-reported quality of life and symptom burden measures in human papillomavirus associated oropharyngeal cancer – A review of the literature and PRO methodology
2021, Oral OncologyCitation Excerpt :In the often quoted study by Ringash et al. used in the HNC literature, 10% was the upper limit of the reported MCIDs (range 4–10%) when laryngectomy patients were asked to rate their HRQL relative to other patients; patients were also more sensitive to improvements than deteriorations (i.e. the MCID was lower for improvements) [43]. This study has been variably interpreted leading to variations in the FACT-HN MCID ranging from 6 to 14 (4–10%) [49–51]. Where patients have been asked to prioritise their treatment outcomes, preservation of swallowing ranks highest amongst functional outcomes in both HPVOPC and unselected HNC cohorts [52,53] supporting the increasing popularity of the MDADI as a primary outcome of interest in HNC studies.
Quality of Life for Patients With Favorable-Risk HPV-Associated Oropharyngeal Cancer After De-intensified Chemoradiotherapy
2019, International Journal of Radiation Oncology Biology PhysicsCitation Excerpt :The standard approach for locally advanced disease is concurrent chemoradiotherapy with a cumulative radiation therapy (RT) dose of 70 gray (Gy) and high-dose cisplatin (300 mg/m2). However, this treatment results in long-term morbidity that can affect quality of life (QOL),6-8 which is a significant issue given the excellent prognosis for these patients. As a result, there is a great interest in de-intensifying treatment of this population of patients, with the goal of preserving cancer control while reducing treatment-related morbidity.