Dataset Information

Concurrent cisplatin or cetuximab with radiotherapy for HPV-positive oropharyngeal cancer: Medical resource use, costs, and quality-adjusted survival from the De-ESCALaTE HPV trial.

ABSTRACT:

Background

The De-ESCALaTE HPV trial confirmed the dominance of cisplatin over cetuximab for tumour control in patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC). Here, we present the analysis of health-related quality of life (HRQoL), resource use, and health care costs in the trial, as well as complete 2-year survival and recurrence.

Materials and methods

Resource use and HRQoL data were collected at intervals from the baseline to 24 months post treatment (PT). Health care costs were estimated using UK-based unit costs. Missing data were imputed. Differences in mean EQ-5D-5L utility index and adjusted cumulative quality-adjusted life years (QALYs) were compared using the Wilcoxon signed-rank test and linear regression, respectively. Mean resource usage and costs were compared through two-sample t-tests.

Results

334 patients were randomised to cisplatin (n = 166) or cetuximab (n = 168). Two-year overall survival (97·5% vs 90·0%, HR: 3.268 [95% CI 1·451 to 7·359], p = 0·0251) and recurrence rates (6·4% vs 16·0%, HR: 2·67 [1·38 to 5·15]; p = 0·0024) favoured cisplatin. No significant differences in EQ-5D-5L utility scores were detected at any time point. At 24 months PT, mean difference was 0·107 QALYs in favour of cisplatin (95% CI: 0·186 to 0·029, p = 0·007) driven by the mortality difference. Health care costs were similar across all categories except the procurement cost and delivery of the systemic agent, with cetuximab significantly more expensive than cisplatin (£7779 [P < 0.001]). Consequently, total costs at 24 months PT averaged £13517 (SE: £345) per patient for cisplatin and £21064 (SE: £400) for cetuximab (mean difference £7547 [95% CI: £6512 to £8582]).

Conclusions

Cisplatin chemoradiotherapy provided more QALYs and was less costly than cetuximab bioradiotherapy, remaining standard of care for nonsurgical treatment of HPV-positive OPSCC.

SUBMITTER: Jones DA

PROVIDER: S-EPMC6947474 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

Concurrent cisplatin or cetuximab with radiotherapy for HPV-positive oropharyngeal cancer: Medical resource use, costs, and quality-adjusted survival from the De-ESCALaTE HPV trial.

Jones David A DA Mistry Pankaj P Dalby Matthew M Fulton-Lieuw Tessa T Kong Anthony H AH Dunn Janet J Mehanna Hisham M HM Gray Alastair M AM

European journal of cancer (Oxford, England : 1990) 20191130

<h4>Background</h4>The De-ESCALaTE HPV trial confirmed the dominance of cisplatin over cetuximab for tumour control in patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC). Here, we present the analysis of health-related quality of life (HRQoL), resource use, and health care costs in the trial, as well as complete 2-year survival and recurrence.<h4>Materials and methods</h4>Resource use and HRQoL data were collected at intervals from the baseline to 24 ...[more]

PMID: 31794928

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Project description:BackgroundThe incidence of human papillomavirus (HPV)-positive oropharyngeal cancer, a disease affecting younger patients, is rapidly increasing. Cetuximab, an epidermal growth factor receptor inhibitor, has been proposed for treatment de-escalation in this setting to reduce the toxicity of standard cisplatin treatment, but no randomised evidence exists for the efficacy of this strategy.MethodsWe did an open-label randomised controlled phase 3 trial at 32 head and neck treatment centres in Ireland, the Netherlands, and the UK, in patients aged 18 years or older with HPV-positive low-risk oropharyngeal cancer (non-smokers or lifetime smokers with a smoking history of <10 pack-years). Eligible patients were randomly assigned (1:1) to receive, in addition to radiotherapy (70 Gy in 35 fractions), either intravenous cisplatin (100 mg/m2 on days 1, 22, and 43 of radiotherapy) or intravenous cetuximab (400 mg/m2 loading dose followed by seven weekly infusions of 250 mg/m2). The primary outcome was overall severe (grade 3-5) toxicity events at 24 months from the end of treatment. The primary outcome was assessed by intention-to-treat and per-protocol analyses. This trial is registered with the ISRCTN registry, number ISRCTN33522080.FindingsBetween Nov 12, 2012, and Oct 1, 2016, 334 patients were recruited (166 in the cisplatin group and 168 in the cetuximab group). Overall (acute and late) severe (grade 3-5) toxicity did not differ significantly between treatment groups at 24 months (mean number of events per patient 4·8 [95% CI 4·2-5·4] with cisplatin vs 4·8 [4·2-5·4] with cetuximab; p=0·98). At 24 months, overall all-grade toxicity did not differ significantly either (mean number of events per patient 29·2 [95% CI 27·3-31·0] with cisplatin vs 30·1 [28·3-31·9] with cetuximab; p=0·49). However, there was a significant difference between cisplatin and cetuximab in 2-year overall survival (97·5% vs 89·4%, hazard ratio 5·0 [95% CI 1·7-14·7]; p=0·001) and 2-year recurrence (6·0% vs 16·1%, 3·4 [1·6-7·2]; p=0·0007).InterpretationCompared with the standard cisplatin regimen, cetuximab showed no benefit in terms of reduced toxicity, but instead showed significant detriment in terms of tumour control. Cisplatin and radiotherapy should be used as the standard of care for HPV-positive low-risk patients who are able to tolerate cisplatin.FundingCancer Research UK.

Project description:BACKGROUND:Addition of nimotuzumab to weekly cisplatin and radiation improves outcomes in head and neck cancer. HPV negative oropharyngeal cancer has unsatisfactory treatment outcomes and is a candidate for escalation of treatment. We wanted to determine whether the addition of nimotuzumab to cisplatin-radiation could improve outcomes in these poor-risk tumors. METHODS:This was a subgroup analysis of a phase 3 randomized study. In this study, locally advanced head and neck cancer patients undergoing definitive chemoradiation were randomly allocated to weekly cisplatin (30 mg/m2 IV)- radiation (66-70 Gy) {CRT arm} or nimotuzumab (200 mg weekly) -weekly cisplatin (30 mg/m2)-radiation (66-70 Gy) {NCRT arm}. The data of HPV negative oropharyngeal cancer was extracted from the database of this study for the analysis. HPV testing was done with p16 immunohistochemistry (IHC) staining and reported according to the CAP criteria. The outcomes assessed were progression-free survival (PFS), disease-free survival (DFS), locoregional control, and overall survival (OS). Interaction test was performed between the study arms and HPV status prior to doing any HPV specific analysis for each of the studied outcomes. Kaplan Meier estimates for 2 year OS with 95%CI was calculated. The hazard ratio was obtained using COX regression analysis. RESULTS:We had 187 HPV negative oropharyngeal cancers, 91 in the CRT arm and 96 in NCRT arm. The interaction test was significant for PFS (p = 0.000), locoregional control (p = 0.007) and overall survival (p = 0.002) but not for DFS (p = 0.072). The 2- year PFS was 31.5% (95%CI 21.5-42) in CRT arm versus 57.2% (95%CI 45.8-67.1) in NCRT arm (HR -0.54; 95%CI 0.36-0.79, p = 0.002). The 2-year LRC was 41.4% (95%CI 29.8-52.6) in the CRT arm versus in 60.4% (95%CI 48.7-70.2) in the NCRT arm (HR -0.61; 95%CI 0.4-0.94, p = 0.024). The addition of nimotuzumab also lead to an improvement in 2-year OS from 39.0% (95%CI 28.4-49.6) to 57.6% (95%CI 46.3-67.4) (HR-0.63, 95%CI 0.43-0.92, p = 0.018). CONCLUSIONS:The addition of nimotuzumab to weekly cisplatin-radiation improves outcomes inclusive of OS in HPV negative oropharyngeal cancers.

Project description:In this open-label phase I study, the maximum-tolerated dose of cetuximab with concurrent chemoradiotherapy (C-CRT) in stage III non-small-cell lung cancer together with individualized, isotoxic accelerated radiotherapy (RT) was investigated.Patients with stage III non-small-cell lung cancer, World Health Organization performance status 0-1, forced expiratory volume in 1 second more than 50%, carbon monoxide diffusing capacity more than 50%, weight loss less than 10%, and no severe comorbidity were enrolled. Patients without progression after one to two cycles of gemcitabine-carboplatin were included and treated with cetuximab 400 mg/kg d7 and 250 mg/kg weekly together with RT and cisplatin (50 mg/m d1, 8; 40 mg/m d22)-vinorelbine for 5 weeks. Vinorelbine was escalated in three steps; (1) 10 mg/m d1, 8 and 8 mg/m d22, 29; (2) 20 mg/m d1, 8 and 8 mg/m d22, 29; (3) 20 mg/m d1, 8; 15 mg/m d22, 29. An individualized prescribed RT dose based on normal tissue dose constraints was applied (e.g., mean lung dose 19 Gy). The primary endpoint was the maximum-tolerated dose 3 months after the end of C-CRT; secondary endpoints were toxicity and metabolic response as assessed by positron emission tomography.Between September 2007 and October 2010, 25 patients (12 men, 13 women, mean age 59 years) were included. The mean RT dose was 62 ± 6.6 Gy. The vinorelbine dose could be escalated to dose level 3. Twelve of 25 patients experienced greater than or equal to grade 3 toxicity (esophagitis 3, rash 1, diarrhea 1, cough 1, dyspnea 1, vomiting 1, and pulmonary embolism 1). No dose-limiting toxicities were observed. One patient with a complete pathological response in dose level 3 developed a fatal hemoptysis 4 months after RT. Metabolic remissions were observed in 19 of 22 patients.C-CRT with cetuximab and cisplatin-vinorelbine is safe to deliver at full dose. The recommended phase II dose is therefore cetuximab 400 mg/m d7 and 250 mg/m weekly, cisplatin 50 mg/m d1, 8; 40 mg/m d22 and vinorelbine 20 mg/m d1, 8; 15 mg/m d22, 29 for 5 weeks together with RT.

Dataset Information

Concurrent cisplatin or cetuximab with radiotherapy for HPV-positive oropharyngeal cancer: Medical resource use, costs, and quality-adjusted survival from the De-ESCALaTE HPV trial.

Background

Materials and methods

Results

Conclusions

Publications

Concurrent cisplatin or cetuximab with radiotherapy for HPV-positive oropharyngeal cancer: Medical resource use, costs, and quality-adjusted survival from the De-ESCALaTE HPV trial.

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