Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2022 Feb;5(2):e1467.
doi: 10.1002/cnr2.1467. Epub 2021 Jun 22.

Observational, prospective, phase 4 study in patients with first-line recurrent and/or metastatic squamous cell carcinoma of the head and neck treated with cetuximab and platinum-based therapy: DIRECT

Joël Guigay  1 , Emmanuel Chamorey  1 , Gautier Lefebvre  2 , Maciej Rotarski  3 , Jean-Philippe Wagner  4 , Emmanuel Blot  5   6 , Marc Alfonsi  7 , Audrey Seronde  8 , Jeltje Schulten  9 , Frédéric Peyrade  1 , Christophe Le Tourneau  10   11   12
Affiliations
Clinical Trial

Observational, prospective, phase 4 study in patients with first-line recurrent and/or metastatic squamous cell carcinoma of the head and neck treated with cetuximab and platinum-based therapy: DIRECT

Joël Guigay et al. Cancer Rep (Hoboken). 2022 Feb.

Abstract

Background: Cetuximab plus platinum-based therapy (PBT) followed by cetuximab maintenance until progression (EXTREME) is a guideline-recommended first-line treatment option in recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). DIRECT (Dose Intensity RElative to CeTuximab) was the first phase 4 observational study evaluating EXTREME administration in the real-world setting.

Aims: The primary aim of this study was to assess the relative dose intensity of cetuximab in patients with R/M SCCHN treated with first-line cetuximab according to the EXTREME regimen.

Methods and results: Patients were ≥18 years old and eligible to receive cetuximab/PBT. Primary endpoint was cetuximab relative dose intensity (RDI). Of prospectively enrolled patients (n = 157), 119 received ≥1 cycle of EXTREME. Practices differing from the EXTREME trial were 5-fluorouracil omission (14%), maintenance cetuximab given every other week (54%), prior cetuximab, disease-free interval <6 months. 64% of patients reached cetuximab RDI ≥80%; mean cetuximab RDI was 88%. 46% of patients received maintenance cetuximab (mean RDI, 91%). Median progression-free survival and overall survival were 4.5 and 9.4 months. No new/unexpected safety findings were observed.

Conclusions: The DIRECT study showed that first-line cetuximab plus PBT was a feasible, beneficial first-line treatment regimen in patients with R/M SCCHN in the real-world setting.

Keywords: 5-fluorouracil; carboplatin; cetuximab; cisplatin; head and neck neoplasms; palliative care.

PubMed Disclaimer

Conflict of interest statement

Joël Guigay has served on advisory boards for AstraZeneca, Bristol Myers Squibb, Innate Pharma, and Merck KGaA and has received grants for research from GSK, Bristol Myers Squibb, Chugai, and Merck KGaA. Audrey Seronde is an employee of Merck Santé SAS, Lyon, France, an affiliate of Merck KGaA, Darmstadt, Germany. Jeltje Schulten is an employee of Merck KGaA, Darmstadt, Germany. Christophe Le Tourneau has an advisory role for Merck KGaA.

Figures

FIGURE 1
FIGURE 1
(A) Progression‐free survival of the prospective population of DIRECT (patients who received ≥1 dose of cetuximab; N = 157). (B) Overall survival of the prospective population of DIRECT (patients who received ≥1 dose of cetuximab; N = 157)
See this image and copyright information in PMC

References

    1. Price KA, Cohen EE. Current treatment options for metastatic head and neck cancer. Curr Treat Options Oncol. 2012;13:35‐46. - PubMed
    1. Vermorken JB, Mesia R, Rivera F, et al. Platinum‐based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008;359:1116‐1127. - PubMed
    1. Vermorken JB, Psyrri A, Mesia R, et al. Impact of tumor HPV status on outcome in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck receiving chemotherapy with or without cetuximab: retrospective analysis of the phase III EXTREME trial. Ann Oncol. 2014;25:801‐807. - PMC - PubMed
    1. Vermorken JB, Specenier P. Optimal treatment for recurrent/metastatic head and neck cancer. Ann Oncol. 2010;21(7 suppl):vii252‐vii261. - PubMed
    1. Tourneau CL, Ghiani M, Cau MC, et al. The observational ENCORE study: cetuximab + platinum‐based therapy (PBT) for first‐line (1L) treatment of patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). Ann Oncol. 2017;28(5 suppl):v372‐v394.

Publication types