PD-034: Data from Pet Neck and GSK trials: Regional and geographic variability in HPV-associated oropharyngeal cancer

Mehanna, Hisham M.; Robinson, Max; Powell, Nicholas; Paleri, Vinidh; Hartley, A.; Fresco, L.; Al-Booz, Hoda; Junor, Elizabeth; Roberts, Sophie; Harrington, Kevin J.

doi:10.1016/s0167-8140(15)34794-0

Cited by 8 publications

(12 citation statements)

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“…Three previous head-to-head comparisons between cisplatin-based chemoradiation and cetuximab-based bioradiotherapy for patients with HPV-positive oropharyngeal cancer noted inferior locoregional control rates in the respective cetuximab arms. [38][39][40] Our data support previous findings from a SEER-based analysis in which cetuximab-based bioradiotherapy was found to be associated with comparable survival to radiotherapy alone, whereas chemoradiation was associated with superior survival in older patients with HNSCC after adjusting for patient-and tumor-related baseline variables. 41 Multiple different chemotherapy regimens have been administered in the patient cohort analyzed in this study, reflecting the considerable heterogeneity between different treatment centers, especially given the lack of clear evidence or treatment recommendations in older adults with HNSCCs.…”

Section: Discussionsupporting

confidence: 87%

Evaluation of Concomitant Systemic Treatment in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Radiotherapy

et al. 2023

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ImportanceThe number of older adults with head and neck squamous cell carcinoma (HNSCC) is increasing, and these patients are underrepresented in clinical trials. It is unclear whether the addition of chemotherapy or cetuximab to radiotherapy is associated with improved survival in older adults with HNSCC.ObjectiveTo examine whether the addition of chemotherapy or cetuximab to definitive radiotherapy is associated with improved survival in patients with locoregionally advanced (LA) HNSCC.Design, Setting, and ParticipantsThe Special Care Patterns for Elderly HNSCC Patients Undergoing Radiotherapy (SENIOR) study is an international, multicenter cohort study including older adults (≥65 years) with LA-HNSCCs of the oral cavity, oropharynx/hypopharynx, or larynx treated with definitive radiotherapy, either alone or with concomitant systemic treatment, between January 2005 and December 2019 at 12 academic centers in the US and Europe. Data analysis was conducted from June 4 to August 10, 2022.InterventionsAll patients underwent definitive radiotherapy alone or with concomitant systemic treatment.Main Outcomes and MeasuresThe primary outcome was overall survival. Secondary outcomes included progression-free survival and locoregional failure rate.ResultsAmong the 1044 patients (734 men [70.3%]; median [IQR] age, 73 [69-78] years) included in this study, 234 patients (22.4%) were treated with radiotherapy alone and 810 patients (77.6%) received concomitant systemic treatment with chemotherapy (677 [64.8%]) or cetuximab (133 [12.7%]). Using inverse probability weighting to attribute for selection bias, chemoradiation was associated with longer overall survival than radiotherapy alone (hazard ratio [HR], 0.61; 95% CI, 0.48-0.77; P &lt; .001), whereas cetuximab-based bioradiotherapy was not (HR, 0.94; 95% CI, 0.70-1.27; P = .70). Progression-free survival was also longer after the addition of chemotherapy (HR, 0.65; 95% CI, 0.52-0.81; P &lt; .001), while the locoregional failure rate was not significantly different (subhazard ratio, 0.62; 95% CI, 0.30-1.26; P = .19). The survival benefit of the chemoradiation group was present in patients up to age 80 years (65-69 years: HR, 0.52; 95% CI, 0.33-0.82; 70-79 years: HR, 0.60; 95% CI, 0.43-0.85), but was absent in patients aged 80 years or older (HR, 0.89; 95% CI, 0.56-1.41).Conclusions and RelevanceIn this cohort study of older adults with LA- HNSCC, chemoradiation, but not cetuximab-based bioradiotherapy, was associated with longer survival compared with radiotherapy alone.

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Section: Discussionsupporting

confidence: 87%

Evaluation of Concomitant Systemic Treatment in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Radiotherapy

et al. 2023

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“…Although multiple studies have shown treatment with carboplatin 18 and cetuximab [4][5][6][7]19,20 to be inferior to cisplatinbased CRT for HNSCC, to our knowledge, cetuximab-based and carboplatin-based CRT have never been compared in a large population-based cohort study. In more than 8000 US veterans with locally advanced HNSCC who were undergoing treatment with definitive CRT from 2006 to 2020, almost a third of patients were ineligible to receive treatment with cisplatin and received cetuximab-based or carboplatin-based radiosensitization.…”

Section: Discussionmentioning

confidence: 99%

“…[21][22][23] Survival estimates in cisplatin-treated patients in the cohort were comparable with outcomes in various pivotal trials of definitive CRT for HNSCC. 4,24,25 Unsurprisingly, because of a combination of known inferior efficacy [4][5][6][7] and patient selection factors, patients treated with noncisplatin regimens had worse survival than cisplatin-treated patients. Patients excluded because of receipt of more than 1 type of systemic therapy, many of whom first received treatment with cisplatin and then were transitioned to use of carboplatin-based or cetuximab-based therapy, displayed intermediate survival.…”

Section: Discussionmentioning

confidence: 99%

“…Cetuximab and carboplatinfluorouracil with radiotherapy (RT) have been associated with improved survival compared with RT alone in randomized clinical trials. [1][2][3] While multiple trials have demonstrated that cetuximab is inferior to cisplatin-based CRT, particularly in human papillomavirus (HPV)-related cancers, [4][5][6][7] to our knowledge, cetuximab and carboplatin-based radiosensitization have never been compared head-to-head in a prospective trial. Retrospective studies comparing noncisplatin CRT regimens for HNSCC have largely shown improved progression-free and overall survival with carboplatin compared with cetuximab.…”

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confidence: 99%

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Cetuximab-Based vs Carboplatin-Based Chemoradiotherapy for Patients With Head and Neck Cancer

Sun

Candelieri-Surette

Anglin-Foote

et al. 2022

JAMA Otolaryngol Head Neck Surg

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ImportanceCetuximab-based and carboplatin-based chemoradiotherapy (CRT) are often used for patients with locally advanced head and neck cancer who are ineligible for cisplatin. There are no prospective head-to-head data comparing cetuximab-based and carboplatin-based regimens for radiosensitization.ObjectiveTo compare survival with cetuximab-based and carboplatin-based CRT in locally advanced head and neck squamous cell carcinoma (HNSCC).Design, Setting, and ParticipantsThis cohort study included US veterans who received a diagnosis of HNSCC between January 2006 and December 2020 and were treated with systemic therapy and radiation. Data cutoff was March 1, 2022 and data analysis was conducted from April-May 2022.ExposuresCisplatin, cetuximab, or carboplatin-based systemic therapy as captured in VA medication data and cancer registry.Main Outcomes and MeasuresOverall survival by systemic therapy was estimated using Kaplan-Meier methods. We used propensity score and inverse probability weighting to achieve covariate balance between cetuximab-treated and carboplatin-treated patients and used Cox regression to estimate cause-specific hazard ratios of death associated with carboplatin vs cetuximab. We also performed subgroup analyses of patients with oropharynx vs nonoropharynx primary sites.ResultsA total of 8290 patients (median [IQR] age, 63 [58-68] years; 8201 men [98.9%]; 1225 [15.8%] Black or African American and 6424 [82.6%] White individuals) with nonmetastatic HNSCC were treated with CRT with cisplatin (5566 [67%]), carboplatin (1231 [15%]), or cetuximab (1493 [18%]). Compared with cisplatin-treated patients, patients treated with carboplatin and cetuximab were older with worse performance status scores and higher comorbidity burden. Median (IQR) overall survival was 74.4 (22.3-162.2) months in patients treated with cisplatin radiotherapy (RT), 43.4 (15.3-123.8) months in patients treated with carboplatin RT, and 31.1 (12.4-87.8) months in patients treated with cetuximab RT. After propensity score and inverse probability weighting, carboplatin was associated with improved overall survival compared with cetuximab (cause-specific hazard ratio, 0.85; 95% CI, 0.78-0.93; P = .001). This difference was prominent in the oropharynx subgroup.Conclusions and RelevanceIn this cohort study of a US veteran population with HNSCC undergoing treatment with CRT, almost a third of patients were ineligible to receive treatment with cisplatin and received cetuximab-based or carboplatin-based radiosensitization. After propensity score matching, carboplatin-based systemic therapy was associated with 15% improvement in overall survival compared with cetuximab, suggesting that carboplatin may be the preferred radiosensitizer, particularly in oropharynx cancers.

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“…fforts to de-escalate treatment for oropharyngeal squamous cell carcinomas (OPSCC) have largely focused on mitigating toxicities related to functional outcomes such as dysphagia and xerostomia. [1][2][3] Several large epidemiologic studies have shown that survivors of head and neck cancer also face substantial competing risks from cardiovascular and cerebrovascular disease, which can equal or exceed their risk of cancer-specific mortality. [4][5][6][7] Cancer therapy may potentiate these risks: radiation therapy to the neck has been associated with increased rates of carotid artery stenosis, 8 carotid intima medial thickness, 9 and stroke in both younger 10,11 and older 12,13 patient cohorts.…”

mentioning

confidence: 99%

Association Between Up-front Surgery and Risk of Stroke in US Veterans With Oropharyngeal Carcinoma

Sun

Brody

Candelieri

et al. 2022

JAMA Otolaryngol Head Neck Surg

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ImportanceCardiovascular events are an important cause of morbidity in patients with oropharyngeal squamous cell carcinoma (OPSCC). Radiation and chemotherapy have been associated with increased risk of stroke; up-front surgery allows the opportunity for (chemo)radiotherapy de-escalation.ObjectiveTo evaluate whether up-front surgery was associated with decreased stroke risk compared to nonsurgical treatment for OPSCC.Design, Setting, and ParticipantsThis cohort study was conducted at the US Veterans Health Administration and examined US veterans diagnosed with nonmetastatic OPSCC from 2000 to 2020. Data cutoff was September 17, 2021, and data analysis was performed from October 2021 to February 2022.ExposuresUp-front surgical treatment or definitive (chemo)radiotherapy as captured in cancer registry.Main Outcomes and MeasuresCumulative incidence of stroke, accounting for death as a competing risk; and association between up-front surgery and stroke risk. After generating propensity scores for the probability of receiving surgical treatment and using inverse probability weighting (IPW) to construct balanced pseudo-populations, Cox regression was used to estimate a cause-specific hazard ratio (csHR) of stroke associated with surgical vs nonsurgical treatment.ResultsOf 10 436 patients, median (IQR) age was 61 (56-67) years; 10 329 (99%) were male; 1319 (13%) were Black, and 7823 (75%) were White; 2717 received up-front surgery, and 7719 received nonsurgical therapy with definitive (chemo)radiotherapy. The 10-year cumulative incidence of stroke was 12.5% (95% CI, 11.8%-13.3%) and death was 57.3% (95% CI, 56.2%-58.4%). Surgical patients who also received (chemo)radiotherapy had shorter radiation and chemotherapy courses than nonsurgical patients. After propensity score and IPW, the csHR of stroke for surgical treatment was 0.77 (95% CI, 0.66-0.91). This association was consistent across subgroups defined by age and baseline cardiovascular risk factors.Conclusions and RelevanceIn this cohort study, up-front surgical treatment was associated with a 23% reduced risk of stroke compared with definitive (chemo)radiotherapy. These findings present an important additional risk-benefit consideration to factor into treatment decisions and patient counseling and should motivate future studies to examine cardiovascular events in this high-risk population.

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PD-034: Data from Pet Neck and GSK trials: Regional and geographic variability in HPV-associated oropharyngeal cancer

Cited by 8 publications

References 0 publications

Evaluation of Concomitant Systemic Treatment in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Radiotherapy

Evaluation of Concomitant Systemic Treatment in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Radiotherapy

Cetuximab-Based vs Carboplatin-Based Chemoradiotherapy for Patients With Head and Neck Cancer

Association Between Up-front Surgery and Risk of Stroke in US Veterans With Oropharyngeal Carcinoma

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