Survival predictors and outcomes of patients with recurrent and/or metastatic head and neck cancer treated with chemotherapy plus cetuximab as first-line therapy: A real-world retrospective study

Pontes, F.; Garcia, Ana Rita; Domingues, I.; Sousa, Maria João; Felix, Rita; Amorim, C.V.V.; Salgueiro, F.R.; Mariano, M.; Teixeira, Margarida

doi:10.1016/j.ctarc.2021.100375

Cited by 8 publications

(7 citation statements)

References 15 publications

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“…They are the sixth most frequent malignancies with ~700,000 new cases being diagnosed worldwide each year [ 2 ]. Due to the fact that most tumors are diagnosed at locally-advanced stages [ 1 ], as well as to treatment failure despite recent medical progressions [ 3 ], the five-year overall survival of patients with HNSCC is poor (<40–50%) [ 4 ]. The management of the majority of patients with HNSCC relies on a multimodal approach that involves surgery (in amenable patients), followed by adjuvant radiotherapy or platinum-based (e.g., cisplatin or carboplatin, and 5-fluorouracil) chemoradiotherapy [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

The EXTREME Regimen Associating Cetuximab and Cisplatin Favors Head and Neck Cancer Cell Death and Immunogenicity with the Induction of an Anti-Cancer Immune Response

Azevedo

Mourtada

Bour

et al. 2022

Cells

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(1) Background: The first line of treatment for recurrent/metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) has recently evolved with the approval of immunotherapies that target the anti-PD-1 immune checkpoint. However, only about 20% of the patients display a long-lasting objective tumor response. The modulation of cancer cell immunogenicity via a treatment-induced immunogenic cell death is proposed to potentially be able to improve the rate of patients who respond to immune checkpoint blocking immunotherapies. (2) Methods: Using human HNSCC cell line models and a mouse oral cancer syngeneic model, we have analyzed the ability of the EXTREME regimen (combination therapy using the anti-EGFR cetuximab antibody and platinum-based chemotherapy) to modify the immunogenicity of HNSCC cells. (3) Results: We showed that the combination of cetuximab and cisplatin reduces cell growth through both cell cycle inhibition and the induction of apoptotic cell death independently of p53. In addition, different components of the EXTREME regimen were found to induce, to a variable extent, and in a cell-dependent manner, the emission of mediators of immunogenic cell death, including calreticulin, HMGB1, and type I Interferon-responsive chemokines. Interestingly, cetuximab alone or combined with the IC 50 dose of cisplatin can induce an antitumor immune response in vivo, but not when combined with a high dose of cisplatin. (4) Conclusions: Our observations suggest that the EXTREME protocol or cetuximab alone are capable, under conditions of moderate apoptosis induction, of eliciting the mobilization of the immune system and an anti-tumor immune response in HNSCC.

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Section: Introductionmentioning

confidence: 99%

The EXTREME Regimen Associating Cetuximab and Cisplatin Favors Head and Neck Cancer Cell Death and Immunogenicity with the Induction of an Anti-Cancer Immune Response

Azevedo

Mourtada

Bour

et al. 2022

Cells

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“…Les formes métastatiques de novo représentent 10 à 25%11,12 . Un traitement médical palliatif est indiqué pour les cancers métastatiques et les rechutes locorégionales et/ou métastatiques non accessibles à un traitement curatif.La médiane de survie de ces cancers de stade avancé est de 6 à 15 mois13,14 . Elle est conditionnée par des facteurs pronostiques péjoratifs tels que le mauvais état général, la dénutrition, l'absence de réponse à la chimiothérapie de première ligne, un délai de rechute de moins de 6 mois après un traitement curatif, les tumeurs HPV ou PD L1 négatives15 .…”

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Impact of previous nivolumab treatment on the response to taxanes in patients with recurrent/metastatic head and neck squamous cell carcinoma

Guiard

Clatot

Even

et al. 2021

European Journal of Cancer

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“…Clinically, real-world data in recurrent and/or metastatic HNSCC have overall shown poor outcomes with reported median progression-free survivals of 4.8-7.1 months and OS 7.1-11.7 months. 25,26 Analysis of our MDACC clinical data set confirmed that clinical outcomes in HRAS-mutant HNSCC, overall, are poor, with a high rate of relapse following primary definitive treatment and relatively short DFS (4.0 months) and OS (15.0 months). Tipifarnib has demonstrated encouraging efficacy in patients with HRAS-mutant HNSCC, 9 and the use of tipifarnib in the Kura data set demonstrated improved OS compared with the MD Anderson cohort.…”

Section: Discussionmentioning

confidence: 72%

HRAS Mutations Define a Distinct Subgroup in Head and Neck Squamous Cell Carcinoma

Coleman

Marcelo

Hopkins³

et al. 2023

JCO Precision Oncology

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PURPOSE In head and neck squamous cell carcinoma (HNSCC), HRAS mutation is a new actionable oncogene driver. We aimed to evaluate HRAS mutational variants, comutation profile, and survival outcomes of this molecularly defined population. METHODS We leveraged four deidentified patient data sets with HRAS-mutant HNSCC, MD Anderson Cancer Center, Kura Oncology, Inc trial, Foundation Medicine, and American Association for Cancer Research GENIE v.12. Patient demographic information and clinical courses were extracted, when available, in addition to HRAS mutation type and co-occurring mutations. Survival outcomes were analyzed (Kaplan-Meier method). RESULTS Two hundred forty-nine patients with HRAS-mutant HNSCC were identified from the four data sets. Median age ranged from 55 to 65 years, with a higher frequency in male patients (64%); the majority of HRAS-mutant HNSCC occurred in human papillomavirus–negative HNSCC. HRAS mutation patterns were similar across data sets; G12S was the most common (29%). Treatment responses to tipifarnib were not codon-specific. Compared with wild-type, significantly co-occurring mutations with HRAS were Casp8 (Fisher's exact test, P < .00013), TERT ( P < .0085), and NOTCH1 ( P < .00013). Analysis of clinical courses from the MD Anderson Cancer Center and Kura Oncology, Inc data sets demonstrated poor clinical outcomes with a high rate of recurrence following primary definitive treatment (50%-67% relapse < 6 months) and short disease-free survival (4.0 months; 95% CI, 1.0 to 36.0) and overall survival (OS; 15.0 months; 95% CI, 6.0 to 52.0). Use of tipifarnib in this data set demonstrated improved OS (25.5 months; 95% CI, 18.0 to 48.0). CONCLUSION Oncogenic mutations in HRAS occur in 3%-4% of HNSCC, with G12S being the most frequent. Without targeted therapy, patients with HRAS-mutant HNSCC had poor clinic outcomes; observable trend toward improvement in OS has been noted in cohorts receiving treatments such as tipifarnib. The comutation pattern of HRAS-mutant in HNSCC is distinct, which may provide insight to future therapeutic combination strategies.

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Survival predictors and outcomes of patients with recurrent and/or metastatic head and neck cancer treated with chemotherapy plus cetuximab as first-line therapy: A real-world retrospective study

Cited by 8 publications

References 15 publications

The EXTREME Regimen Associating Cetuximab and Cisplatin Favors Head and Neck Cancer Cell Death and Immunogenicity with the Induction of an Anti-Cancer Immune Response

The EXTREME Regimen Associating Cetuximab and Cisplatin Favors Head and Neck Cancer Cell Death and Immunogenicity with the Induction of an Anti-Cancer Immune Response

Impact of previous nivolumab treatment on the response to taxanes in patients with recurrent/metastatic head and neck squamous cell carcinoma

HRAS Mutations Define a Distinct Subgroup in Head and Neck Squamous Cell Carcinoma

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