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

Abstract

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.

The Association between Patient’s Age and Head and Neck Cancer Treatment Decision—A Population-Based Diagnoses-Related Group-Based Nationwide Study in Germany

“…Cetuximab was licensed in 2004. Cetuximab is especially used in elderly HNC patients with worse performance status who are not ineligible to receive a platinum-based chemotherapy [ 28 ]. Thompson-Harvey et al addressed from the Surveillance, Epidemiology and End Results (SEER), a nationally representative, population-based cancer database, an increasing incidence of higher-stage HNC in the United States.…”

Treatment Considerations for Patients with Locoregionally Advanced Head and Neck Cancer with a Contraindication to Cisplatin

“…It is unclear which alternative regimen, if any, is superior, since there are no randomized trials yet comparing these regimens to each other in the cisplatin-ineligible population. A comparative effectiveness analysis in US veterans with head and neck cancer found that carboplatin-based regimens were associated with superior outcomes compared to cetuximab, after controlling for confounding using propensity score modeling; this effect was mostly driven by patients with oropharyngeal cancer [55]. This study was limited by missing data on HPV status and additional key clinical characteristics, such as smoking and performance status, A separate analysis of the SEER-Medicare database similarly suggested that carboplatinbased regimens were not only superior to cetuximab, but were also similar in efficacy to cisplatin [56].…”

Problems With Interpreting Treatment Effects in Observational Competing Risks Data—Reply

“…In Reply We appreciate the letter by Dr Mell in response to our study, and the opportunity to address the issues raised.…”

“…We acknowledge that residual confounding, as noted in the Limitations section of the Discussion, may be incompletely accounted for by propensity score matching. It is certainly possible that patients receiving cetuximab may have had more severe medical comorbidities at baseline, which were not completely captured and thus could not be adjusted for.…”