Dataset Information

Concurrent Cetuximab and Nivolumab as a Second-Line or beyond Treatment of Patients with Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: Results of Phase I/II Study.

ABSTRACT: We hypothesized the combination of cetuximab and nivolumab would improve survival in recurrent and/or metastatic (R/M) HNSCC by providing synergy in cancer control and evaluated toxicities and efficacy of the combination. Effects of sequential administration of cetuximab and anti-Programmed Cell Death-1 checkpoint inhibitors (CPI) were also explored. Patients who failed at least one line of palliative treatment for incurable HNSCC were treated with cetuximab 500 mg/m2 IV on Day (D)-14 as a lead-in followed by cetuximab 500 mg/m2 IV and nivolumab 240 mg/m2 IV on D1 and D15 every 28-D cycle. Electronic health record-derived real-world data (RWD) were used to explore sequential treatment effects of CPI and cetuximab. A total of 45 evaluable patients were analyzed, and 31/45 (69%) patients had prior exposure to either CPI or cetuximab. The only grade 4 treatment-related adverse event was cetuximab infusion reaction in one patient. The 1-year progression-free survival (PFS) and overall survival (OS) rates were 19% and 44%, respectively. Although patients with no prior CPI (23/45, 51%) showed a trend for more favorable PFS relative to patients with prior CPI (22/45, 49%), the improvement in the 1-year OS did not reach the statistical threshold. For evaluation of sequential CPI and cetuximab treatment effects, we selected RWD-cetuximab cohort with 173 patients and RWD-CPI cohort with 658 patients from 6862 R/M HNSCC. Our result suggested patients treated with RWD-cetuximab after RWD-CPI had worse OS compared to no prior RWD-CPI (HR 1.81, 95% CI 1.02-3.16). Our data suggest the combination of cetuximab and nivolumab is well tolerated. Optimal sequencing of cetuximab and CPI may have an impact in prognosis and requires further evaluation.

SUBMITTER: Chung CH

PROVIDER: S-EPMC7967147 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Concurrent Cetuximab and Nivolumab as a Second-Line or beyond Treatment of Patients with Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: Results of Phase I/II Study.

Chung Christine H CH Bonomi Marcelo M Steuer Conor E CE Li Jiannong J Bhateja Priyanka P Johnson Matthew M Masannat Jude J Song Feifei F Hernandez-Prera Juan C JC Wenig Bruce M BM Molina Helen H Farinhas Joaquim M JM McMullen Caitlin P CP Wadsworth J Trad JT Patel Krupal B KB Kish Julie A JA Muzaffar Jameel J Kirtane Kedar K Rocco James W JW Schell Michael J MJ Saba Nabil F NF

Cancers 20210309 5

We hypothesized the combination of cetuximab and nivolumab would improve survival in recurrent and/or metastatic (R/M) HNSCC by providing synergy in cancer control and evaluated toxicities and efficacy of the combination. Effects of sequential administration of cetuximab and anti-Programmed Cell Death-1 checkpoint inhibitors (CPI) were also explored. Patients who failed at least one line of palliative treatment for incurable HNSCC were treated with cetuximab 500 mg/m<sup>2</sup> IV on Day (D)-14 ...[more]

PMID: 33803335

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Project description:BackgroundPatients with recurrent or metastatic squamous-cell carcinoma of the head and neck after platinum chemotherapy have a very poor prognosis and limited therapeutic options. Nivolumab, an anti-programmed death 1 (PD-1) monoclonal antibody, was assessed as treatment for this condition.MethodsIn this randomized, open-label, phase 3 trial, we assigned, in a 2:1 ratio, 361 patients with recurrent squamous-cell carcinoma of the head and neck whose disease had progressed within 6 months after platinum-based chemotherapy to receive nivolumab (at a dose of 3 mg per kilogram of body weight) every 2 weeks or standard, single-agent systemic therapy (methotrexate, docetaxel, or cetuximab). The primary end point was overall survival. Additional end points included progression-free survival, rate of objective response, safety, and patient-reported quality of life.ResultsThe median overall survival was 7.5 months (95% confidence interval [CI], 5.5 to 9.1) in the nivolumab group versus 5.1 months (95% CI, 4.0 to 6.0) in the group that received standard therapy. Overall survival was significantly longer with nivolumab than with standard therapy (hazard ratio for death, 0.70; 97.73% CI, 0.51 to 0.96; P=0.01), and the estimates of the 1-year survival rate were approximately 19 percentage points higher with nivolumab than with standard therapy (36.0% vs. 16.6%). The median progression-free survival was 2.0 months (95% CI, 1.9 to 2.1) with nivolumab versus 2.3 months (95% CI, 1.9 to 3.1) with standard therapy (hazard ratio for disease progression or death, 0.89; 95% CI, 0.70 to 1.13; P=0.32). The rate of progression-free survival at 6 months was 19.7% with nivolumab versus 9.9% with standard therapy. The response rate was 13.3% in the nivolumab group versus 5.8% in the standard-therapy group. Treatment-related adverse events of grade 3 or 4 occurred in 13.1% of the patients in the nivolumab group versus 35.1% of those in the standard-therapy group. Physical, role, and social functioning was stable in the nivolumab group, whereas it was meaningfully worse in the standard-therapy group.ConclusionsAmong patients with platinum-refractory, recurrent squamous-cell carcinoma of the head and neck, treatment with nivolumab resulted in longer overall survival than treatment with standard, single-agent therapy. (Funded by Bristol-Myers Squibb; CheckMate 141 ClinicalTrials.gov number, NCT02105636 .).

Project description:BackgroundTreatment options for patients with platinum-refractory, recurrent, metastatic head and neck squamous cell carcinoma (r/m HNSCC) are limited and prognosis is poor. The recent CheckMate 141 clinical trial demonstrated that nivolumab, an anti-programmed cell death protein 1 monoclonal antibody, was efficacious in extending the median overall survival (OS) in this patient population compared with standard therapies. We conducted a cost-effectiveness analysis to determine whether nivolumab is a cost-effective treatment in this patient population and examined various subgroups to determine for which, if any, the treatment is more cost-effective.Materials and methodsWe implemented a state transition model for HNSCC with a patient cohort who had tumor progression 6 months after the last dose of platinum-containing chemotherapy and compared the cost-effectiveness of nivolumab with docetaxel. Treatment effect estimates and adverse event rates were obtained from CheckMate 141. Costs, utilities, and other model inputs were gathered from published sources. We used a Canadian perspective, a 5-year time horizon, and a 1.5% discount rate for the analysis.ResultsNivolumab extended mean OS by 4 months compared with docetaxel and resulted in fewer treatment-related adverse events, producing an incremental effectiveness of 0.13 quality-adjusted life years (QALY). The incremental cost of treatment with nivolumab was $18,823. At a willingness-to-pay threshold of $100,000/QALY, nivolumab was not a cost-effective treatment option for r/m HNSCC, with an incremental cost-effectiveness ratio of $144,744/QALY. Nivolumab would be cost-effective if its price was reduced by 20%. Our subgroup analysis seemed to indicate that nivolumab might be cost-effective for tumors with expression of programmed death-ligand 1 >5%.ConclusionWe conclude that although nivolumab offers clinical benefit for the treatment of r/m HNSCC over current regimens, it is not cost-effective based on its list price. We have also established a value-based price estimate for nivolumab to be cost-effective in this patient population. Further study is required to draw a definitive conclusion on biomarkers for cost-effectiveness.Implications for practiceIn health care settings in which cost considerations are a constraint on choice of therapy, patient selection should be carefully considered to maintain efficiency in the system. Until a biomarker for response to therapy is identified for nivolumab, this medication is unlikely to be cost-effective for most patients with recurrent, metastatic head and neck squamous cell carcinoma.

Project description:Cetuximab remains to date the only targeted therapy approved for the treatment of head and neck squamous cell carcinoma (HNSCC). The EGFR pathway plays a key role in the tumorigenesis and progression of this disease as well as in the resistance to radiotherapy (RT). While several anti-EGFR agents have been tested in HNSCC, cetuximab, an IgG1 subclass monoclonal antibody against EGFR, is the only drug with proven efficacy for the treatment of both locoregionally-advanced (LA) and recurrent/metastatic (R/M) disease. The addition of cetuximab to radiotherapy is a validated treatment option in LA-HNSCC. However, its use has been limited to patients who are considered unfit for standard of care chemoradiotherapy (CRT) with single agent cisplatin given the lack of direct comparison of these two regimens in randomized phase III trials and the inferiority suggested by metanalysis and phase II studies. The current use of cetuximab in HNSCC is about to change given the recent results from randomized prospective clinical trials in both the LA and R/M setting. Two phase III studies evaluating RT-cetuximab vs. CRT in Human Papillomavirus (HPV)-positive LA oropharyngeal squamous cell carcinoma (De-ESCALaTE and RTOG 1016) showed inferior overall survival and progression-free survival for RT-cetuximab combination, and therefore CRT with cisplatin remains the standard of care in this disease. In the R/M HNSCC, the EXTREME regimen has been the standard of care as first-line treatment for the past 10 years. However, the results from the KEYNOTE-048 study will likely position the anti-PD-1 agent pembrolizumab as the new first line treatment either alone or in combination with chemotherapy in this setting based on PD-L1 status. Interestingly, cetuximab-mediated immunogenicity through antibody dependent cell cytotoxicity (ADCC) has encouraged the evaluation of combined approaches with immune-checkpoint inhibitors in both LA and R/M-HNSCC settings. This article reviews the accumulated evidence on the role of cetuximab in HNSCC in the past decade, offering an overview of its current impact in the treatment of LA and R/M-HNSCC disease and its potential use in the era of immunotherapy.

Dataset Information

Concurrent Cetuximab and Nivolumab as a Second-Line or beyond Treatment of Patients with Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: Results of Phase I/II Study.

Publications

Concurrent Cetuximab and Nivolumab as a Second-Line or beyond Treatment of Patients with Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: Results of Phase I/II Study.

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