Cisplatin and fluorouracil with or without panitumumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (SPECTRUM): an open-label phase 3 randomised trial

Vermorken, Jan B.; Stöhlmacher-Williams, Jan; Давиденко, Ірина; Licitra, Lisa; Winquist, Eric; Villanueva, Cristian; Foa, Paolo; Rottey, Sylvie; Składowski, Krzysztof; Tahara, Makoto; Pai, V. R.; Faivre, Sandrine; Blajman, C.; Forastiere, Arlene A.; Stein, Brian; Oliner, Kelly S.; Pan, Zhiying; Bach, Bruce Allen

doi:10.1016/s1470-2045(13)70181-5

Cited by 396 publications

(324 citation statements)

References 46 publications

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“…Specifically, there were only two grade 4 adverse events described, both clinically insignificant lymphopenia. This number compares very favorably with prior studies, in which grade 4 adverse event rates ranged typically from 30% to 50% for chemotherapy doublets and triplets administered once every 21 days [4], [8], [12], [13]. Our adverse event (AE) data are consistent with another report of weekly docetaxel and cisplatin in this setting [14].…”

supporting

confidence: 86%

Weekly Docetaxel, Cisplatin, and Cetuximab in Palliative Treatment of Patients with Squamous Cell Carcinoma of the Head and Neck

et al. 2018

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Lessons Learned. Chemotherapy for recurrent, metastatic squamous cell carcinoma of the head and neck need not be known for extreme toxicity.The weekly regimen studied here has been demonstrated to be tolerable and effective.Background.The objective of this study was to establish the response rate, progression‐free survival (PFS) and overall survival (OS), and safety profile of weekly docetaxel, platinum, and cetuximab (TPC) in patients with relapsed or metastatic squamous cell carcinoma of the head and neck (SCCHN).Materials and Methods.Twenty‐nine patients with metastatic or recurrent SCCHN with an Eastern Cooperative Oncology Group (ECOG) performance status <3 were enrolled in an institutional review board‐approved phase II trial. This study permitted prior chemoradiation, radiation, and/or surgery, provided that 3 months had elapsed since the end of the potentially curative treatment. Patients received cisplatin 30 mg/m2 or carboplatin area under the curve (AUC) 2, docetaxel 30 mg/m2, and cetuximab 250 mg/m2 weekly for 3 weeks, followed by a break during the fourth week, for a 28‐day cycle. Planned intrapatient dose modifications were based on individual toxicity.Results.Twenty‐seven patients received TPC and were evaluable for response and toxicity. Rates of complete response (CR), partial response (PR), and confirmed PR were 3%, 52%, and 30%, respectively. The overall objective response rate was 56%. Estimated median PFS and OS were 4.8 and 14.7 months, respectively. The rates of grade 3 and 4 worst‐grade adverse events (AEs) per patient were 85% and 7%, respectively. Dose density through cycle 4 was preserved for all patients; however, treatment beyond cycle 6 with the TPC regimen proved unfeasible.Conclusion.Weekly docetaxel, cisplatin, and cetuximab is an effective regimen for patients with metastatic or recurrent SCCHN. Response rates, PFS, and OS compare favorably with other combination chemotherapy treatments. Grade 4 toxicity rates observed in this study were substantially lower than those described with regimens using less frequent, higher‐dose chemotherapy schedules.

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confidence: 86%

Weekly Docetaxel, Cisplatin, and Cetuximab in Palliative Treatment of Patients with Squamous Cell Carcinoma of the Head and Neck

et al. 2018

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“…Other anti-EGFR antibodies, such as panitumumab and zalutumumab, have been tested in open-label phase III trials in SCC of the head and neck, in combination with cisplatin and fluorouracil (NCT00460265) or together with best supportive care, respectively (NCT00382031; refs. 9,18). These trials show no increase in overall survival when adding the anti-EGFR mAb in the treatment.…”

Section: Introductionmentioning

confidence: 95%

Cetuximab Resistance in Squamous Carcinomas of the Upper Aerodigestive Tract Is Driven by Receptor Tyrosine Kinase Plasticity: Potential for mAb Mixtures

Kjær

Lindsted

Fröhlich

et al. 2016

Molecular Cancer Therapeutics

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Squamous cell carcinomas (SCC) arising in upper parts of the aerodigestive tract are among the leading causes of death worldwide. EGFR has been found to play an essential role in driving the malignancy of SCC of the upper aerodigestive tract (SCCUAT), but, despite this, clinical results using a range of different EGFR-targeted agents have been disappointing. Cetuximab is currently the only EGFR-targeted agent approved by the FDA for treatment of SCCUAT. However, intrinsic and acquired cetuximab resistance is a major problem for effective therapy. Thus, a better understanding of the mechanisms responsible for cetuximab resistance is valuable for development of the next generation of antibody therapeutics. In order to better understand the underlying mechanisms of cetuximab resistance in SCCUAT, we established from cetuximab-sensitive models cell lines with acquired resistance to cetuximab by continuous selective pressure in vitro and in vivo. Our results show that resistant clones maintain partial dependency on EGFR and that receptor tyrosine kinase plasticity mediated by HER3 and IGF1R plays an essential role. A multitarget mAb mixture against EGFR, HER3, and IGF1R was able to overcome cetuximab resistance in vitro. To our surprise, these findings could be extended to include SCCUAT cell lines with intrinsic resistance to cetuximab, suggesting that the triad consisting of EGFR, HER3, and IGF1R plays a key role in SCCUAT. Our results thus provide a rationale for simultaneous targeting of EGFR, HER3, and IGF1R in SCCUAT. Mol Cancer Ther; 15(7); 1614-26. Ó2016 AACR.

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“…Other anti-EGFR monoclonal antibodies currently evaluated in HNSCC include panitumumab, n i m o t u z u m a b a n d z a l u t u m u m a b . A m o n g t h e m , panitumumab has produced modest results when added to platinum based chemotherapy in patients with R/M HNSCC (70). Zalutumumab has demonstrated an OS of 5.3 months and a PFS of 2.1 when administered as monotherapy in patients with platinum refractory R/M HNSCC (71).…”

Section: Monoclonal Antibodiesmentioning

confidence: 99%

The emerging role of immunotherapy in head and neck squamous cell carcinoma (HNSCC): anti-tumor immunity and clinical applications

Economopoulou¹,

Perisanidis²,

Giotakis³

et al. 2016

Ann. Transl. Med.

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Head and neck squamous cell carcinoma (HNSCC) carries a poor prognosis, with low survival rates for advanced stage tumors and minimal improvement in survival trends through the past decades. It is becoming increasingly clear that HNSCC oncogenesis and evolution is characterized by profound immune defects, as cancer cells evade immunosurveillance due to accumulation of genetic mutations and tumor heterogeneity. Improved understanding of the role of the immune system in cancer has led to the identification of novel therapeutic targets, which are being investigated for their potential to provide durable responses. In this review, we will summarize the role of the immune system in HNSCC, the rationale behind immunotherapy strategies and their clinical applications.

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Cisplatin and fluorouracil with or without panitumumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (SPECTRUM): an open-label phase 3 randomised trial

Cited by 396 publications

References 46 publications

Weekly Docetaxel, Cisplatin, and Cetuximab in Palliative Treatment of Patients with Squamous Cell Carcinoma of the Head and Neck

Weekly Docetaxel, Cisplatin, and Cetuximab in Palliative Treatment of Patients with Squamous Cell Carcinoma of the Head and Neck

Cetuximab Resistance in Squamous Carcinomas of the Upper Aerodigestive Tract Is Driven by Receptor Tyrosine Kinase Plasticity: Potential for mAb Mixtures

The emerging role of immunotherapy in head and neck squamous cell carcinoma (HNSCC): anti-tumor immunity and clinical applications

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