Cetuximab, docetaxel, and cisplatin versus platinum, fluorouracil, and cetuximab as first-line treatment in patients with recurrent or metastatic head and neck squamous-cell carcinoma (GORTEC 2014-01 TPExtreme): a multicentre, open-label, randomised, phase 2 trial

Guigay, J.; Aupérin, Anne; Fayette, Jérôme; Sâada-Bouzid, Esma; Lafond, C.; Cequier, Ángel; Geoffrois, Lionnel; Martin, Laurent; Capitain, Olivier; Cupissol, Didier; Castanie, Hélène; Vansteene, Damien; Schafhausen, Philippe; Johnson, Alison; Even, Caroline; Siré, C.; Duplomb, Sophie; Evrard, Camille; Delord, Jean‐Pierre; Laguerre, Brigitte; Zanetta, Sylvie; Chevassus-Clément, Cécile; Fraslin, Aldéric; Louat, Fanny; Sinigaglia, Laura; Keilholz, Ulrich; Bourhis, Jean; Mesı́a, Ricard; Baba-Hamed, Nabil; Babin, E.; Béra, G.; Betrian-Lagarde, Sarah; Blot, Emmanuel; Bompas, Emmanuelle; Borel, Christian; Bouchekoua, Mohamed; Moal, L. Bozec Le; Bruyas, Amandine; Calais, G.; Carpiuc, Ioana; Chapet, S.; Chatellier, Thierry; Chauffert, Bruno; Cheli, Sandrine; Clatot, Florian; Cojocarasu, Oana Zveltlana; Cornelly, Alexandre; Coutté, Alexandre; Dalloz, Pierre; Darloy, Franck; Delhommeau, Melissa; Raucourt, D. De; Debelleix, C.; Debourdeau, Philippe; Dillies-Legrain, Anne Françoise; Dô, Pascal; Dubos-Arvis, Catherine; Ducoulombier, Agnès; Kouri, Claude El; Falkowski, Sabrina; Ferrand, François‐Régis; Gatineau, Michel; Gervais, Radj; Gras, L.; Guillet, Pierre; Hasbini, Ali; Henault, Stéphane; Gómez, Ruth Gabriela Herrera; Huguet, F.; Kaminsky, Marie Christine; Lagrange, Aurélie; Lavau‐Denès, Sandrine; Caer, H. Le; Foll, Christine Le; Lefebvre, G.; Linot, Benjamin; Lopez, Qian; Lortholary, Alain; Matias, Margarida; Mayache-Badis, L.; Minne, Floriane; Mollon, Delphine; Neidhardt, Eve Marie; Pavillet, J.; Peyrade, Fréd́eric; Pointreau, Yohann; Ramée, Jean-François; Rauche, Camille; Richard, Sandrine; Rizzo, Claudia; Rolland, Frédéric; Schlurmann, Friderike; Stefani, Laëtitia; Tassy, Louis; Tazi, Youssef; Théry, Jean-Christophe; Zein, Florida Torti El; Toullec, C.; Tourani, Jean-Marc; Toussaint, Philippe; Vanbockstael, Julie; Vauléon, Élodie; Viret, F.; Waler, Sabine; Atzpodien, Jens; Behrens, Caecilia; Busch, Chia Jung; Dietz, Andreas; Feldmann, Georg; Fietkau, Rainer; Granizka, Thordis; Grewe, Jürgen; Guntinas-Lichinus, Orlando; Hadler-Mikesch, Kristina; Hahn, D; Inhestern, Johanna; Kellner, K.; Klinghammer, Konrad; Kronenberger, R; Lüedtke-Heckenkamp, Kerstin; Ochsenreither, Sebastian; Otremba, Burkhard; Peuker, Caroline Anna; Pirlich, Markus; Rothmann, Frank; Tometten, Mareike; Wohlfarth, Sabine; Zebralla, Veit; Zipfel, Matthias; Klein, Juan Carlos Adansa; Arrazubi, Virginia; Daroqui, Javier Caballero; Castelo, Beatriz; Cirauqui, Beatriz; Hernández, Juan Jesús Cruz; Gallego, Óscar; Docampo, Lara Carmen Iglesias; Pousa, Antonio López; Prado, Maria Martinez Del; Martínez‐Trufero, Javier; Borgoñón, Miguel Pastor; Ruíz, Elísabeth Pérez; Garcı́a, Vanesa; Casadevall, Jordi Rubio; Fernández, Silvia Vázquez

doi:10.1016/s1470-2045(20)30755-5

Cited by 108 publications

(59 citation statements)

References 21 publications

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“…Recently, pembrolizumab has been approved as monotherapy and in combination with platinum-based chemotherapy in firstline treatment of PD-L1 positive r/m SCCHN (4). Moreover, the TPEx protocol with cisplatin, docetaxel and cetuximab has emerged as a highly effective and less toxic regiment than the EXTREME protocol (27). These new options result in a broader therapeutic armamentarium in the first-line setting.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Prognostic Clinical Score for Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Treated With Systemic Therapy Including Cetuximab

et al. 2021

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Cetuximab-based chemoimmunotherapy has been the standard of care for recurrent or metastatic squamous cell carcinoma of the head and neck (r/m SCCHN) for more than a decade. To date, no predictive or prognostic biomarkers have been established to further guide the systemic treatment with cetuximab-based chemoimmunotherapy in r/m SCCHN. Against this background, we retrospectively analyzed clinical and blood-based parameters from 218 r/m SCCHN patients treated with chemoimmunotherapy including cetuximab. Multivariate Cox-regression models were used to assess their prognostic or predictive value. Eastern Co-operative Oncology Group (ECOG) performance status (≥2), older age (≥61.8 years), anemia (hemoglobin <11.80), and increased neutrophil-to-lymphocyte ratio (NLR ≥5.73) were independently and strongly associated with inferior overall survival (OS). To group patients according to risk profiles we established a prognostic clinical score (PCS) that can easily be used in clinical practice. The PCS stratified the cohort into low, intermediate, poor or very poor risk subgroups with median OS times of 23.4, 12.1, 7.5, and 4.0 months, respectively. Patients with low risk PCS had a prolonged progression-free survival (PFS) and increased overall response rate (ORR) under first-line cetuximab-based therapy. Interestingly, only patients with low and intermediate risk benefitted from the more intensive first-line cisplatin/cetuximab combination compared to carboplatin/cetuximab therapy, whereas the intensity of first-line treatment had no impact in the poor and very poor risk subgroups. Following external validation, particularly in the context of newly established first-line options, the PCS may guide clinical decision making and serve for stratification of patients with r/m SCCHN in future clinical trials.

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Section: Discussionmentioning

confidence: 99%

Identification of a Prognostic Clinical Score for Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Treated With Systemic Therapy Including Cetuximab

et al. 2021

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“…Adverse events (AEs) were evaluated and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. DLTs were de ned as grade 3 hyperglycemia despite curative optimal glucose lowering therapy, grade ≥ 3 ALT/AST elevation, ANC < 0.5x10 9 /L lasting more than seven days, bleeding felt to be due to thrombocytopenia, febrile neutropenia (both ANC < 1.0x10 9 /L and fever > 38.5°C), platelets < 25x10 9 /L, diarrhea grade 3, rash grade 4, hypertension grade 3 despite optimal treatment, and any clinically signi cant grade 3 AE related to copanlisib and/or cetuximab.…”

Section: Safety and Tolerabilitymentioning

confidence: 99%

“…6 to 9 months in the absence of treatment) [4]. In the recurrent and/or metastatic setting, rst-line standardof-care therapy include immunotherapy with anti-PD1 agents as single agent or in combination with chemotherapy in most of cases [5][6][7], whereas the combination of cetuximab, an anti-EGFR monoclonal antibody, with chemotherapy remains the standard of care for PD-L1 non-expressing tumors [8,9]. The phosphatidylinositol-3 kinase (PI3K) signaling pathway has been found to play an important role in the pathogenesis of HNSCC [10,11].…”

Section: Introductionmentioning

confidence: 99%

Phase I trial of copanlisib, a selective PI3K inhibitor, in combination with cetuximab in patients with recurrent and/or metastatic head and neck squamous cell carcinoma

et al. 2021

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BackgroundThe phosphatidylinositol-3 kinase pathway is often altered in head and neck squamous cell carcinoma (HNSCC), and is involved in the resistance to EGFR inhibitors. ObjectiveWe investigated the dose-limiting toxicities (DLTs), maximum tolerated dose, pharmacokinetics, and preliminary e cacy of the combination of copanlisib, an intravenous, pan-class I PI3K inhibitor, with the anti-EGFR monoclonal antibody cetuximab in recurrent and/or metastatic HNSCC patients in a phase I dose-escalation trial. Patients and methodsCopanlisib was given intravenously on days 1, 8, and 15 of 28-day cycles at the dose of 45 mg and 30 mg, in combination with standard doses of weekly cetuximab (400 mg/m² loading dose followed by 250 mg/m² on days 8, 15, and 22, and weekly thereafter). ResultsThree patients received copanlisib 45 mg, of whom two experienced grade 3 hyperglycemia during Cycle 1 that met the DLT criteria. Eight patients were then treated with copanlisib at the dose of 30 mg. Because of the occurrence of hyperglycemia, a premedication with metformine was introduced on the day of the injections. No DLTs were reported at this dose level. The trial was stopped early because of the unfavourable toxicity pro le of the combination. Among eight evaluable patients for response, four patients (50%) had disease stabilization according to RECIST1.1 as best response. ConclusionCopanlisib combined with cetuximab demonstrated unfavorable toxicity and limited e cacy in heavily pretreated recurrent and/or metastatic HNSCC patients. NCT02822482, Date of registration: June 2016.

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“…There is no specific recommendation for oropharyngeal tumors and no particularities according to the HPV status [8,44,90]. However, even with a metastatic disease, HPV-positive OPSCC patients still harbor a better prognosis than HPV-negative OPSCC patients [90,91].…”

Section: Recurrent And/or Metastatic Opsccmentioning

confidence: 99%

Current Therapeutic Strategies in Patients with Oropharyngeal Squamous Cell Carcinoma: Impact of the Tumor HPV Status

Bozec

Culié

Poissonnet

et al. 2021

Cancers

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Since there is no published randomized study comparing surgical and non-surgical therapeutic strategies in patients with oropharyngeal squamous cell carcinoma (OPSCC), the therapeutic management of these patients remains highly controversial. While human papillomavirus (HPV)-positive and HPV-negative OPSCC are now recognized as two distinct diseases with different epidemiological, biological, and clinical characteristics, the impact of HPV status on the management of OPSCC patients is still unclear. In this review, we analyze the current therapeutic options in patients with OPSCC, highlighting the most recent advances in surgical and non-surgical therapies, and we discuss the impact of HPV status on the therapeutic strategy.

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Cetuximab, docetaxel, and cisplatin versus platinum, fluorouracil, and cetuximab as first-line treatment in patients with recurrent or metastatic head and neck squamous-cell carcinoma (GORTEC 2014-01 TPExtreme): a multicentre, open-label, randomised, phase 2 trial

Cited by 108 publications

References 21 publications

Identification of a Prognostic Clinical Score for Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Treated With Systemic Therapy Including Cetuximab

Identification of a Prognostic Clinical Score for Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Treated With Systemic Therapy Including Cetuximab

Phase I trial of copanlisib, a selective PI3K inhibitor, in combination with cetuximab in patients with recurrent and/or metastatic head and neck squamous cell carcinoma

Current Therapeutic Strategies in Patients with Oropharyngeal Squamous Cell Carcinoma: Impact of the Tumor HPV Status

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