Weekly paclitaxel, carboplatin, cetuximab, and cetuximab, docetaxel, cisplatin, and fluorouracil, followed by local therapy in previously untreated, locally advanced head and neck squamous cell carcinoma

doi:10.1093/annonc/mdy549

Clinical Trial

. 2019 Mar 1;30(3):471-477.

doi: 10.1093/annonc/mdy549.

Weekly paclitaxel, carboplatin, cetuximab, and cetuximab, docetaxel, cisplatin, and fluorouracil, followed by local therapy in previously untreated, locally advanced head and neck squamous cell carcinoma

R I Haddad¹, E Massarelli², J J Lee³, H Y Lin³, K Hutcheson⁴, J Lewis⁵, A S Garden⁶, G R Blumenschein⁵, W N William⁷, R R Pharaon⁸, R B Tishler⁹, B S Glisson⁵, C Pickering⁴, K A Gold¹⁰, F M Johnson⁵, G Rabinowits¹¹, L E Ginsberg¹², M D Williams¹³, J Myers⁴, M S Kies⁵, V Papadimitrakopoulou¹⁴

Affiliations

¹ Department of Medical Oncology, Dana Farber Cancer Institute, Boston.
² Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston; Department of Medical Oncology and Therapeutics Research, City of Hope Cancer Center, Duarte.
³ Departments of Biostatistics.
⁴ Head and Neck Surgery.
⁵ Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston.
⁶ Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, USA.
⁷ Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston; Oncology Center, Hospital BP, A Beneficencia Portuguesa de São Paulo, São Paulo, Brazil.
⁸ Department of Medical Oncology and Therapeutics Research, City of Hope Cancer Center, Duarte.
⁹ Department of Radiation Oncology, Dana Farber Cancer Institute, Boston.
¹⁰ Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston; Division of Hematology and Oncology, University of California San Diego Moores Cancer Center, La Jolla.
¹¹ Department of Medical Oncology, Dana Farber Cancer Institute, Boston; Department of Head and Neck Oncology, Baptist Health South Florida, Coral Gables.
¹² Departments of Diagnostic Radiology.
¹³ Pathology, University of Texas MD Anderson Cancer Center, Houston, USA.
¹⁴ Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston. Electronic address: vpapadim@mdanderson.org.

PMID: 30596812
PMCID: PMC7360148
DOI: 10.1093/annonc/mdy549

Clinical Trial

Weekly paclitaxel, carboplatin, cetuximab, and cetuximab, docetaxel, cisplatin, and fluorouracil, followed by local therapy in previously untreated, locally advanced head and neck squamous cell carcinoma

R I Haddad et al. Ann Oncol. 2019.

. 2019 Mar 1;30(3):471-477.

doi: 10.1093/annonc/mdy549.

Authors

Affiliations

¹ Department of Medical Oncology, Dana Farber Cancer Institute, Boston.
² Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston; Department of Medical Oncology and Therapeutics Research, City of Hope Cancer Center, Duarte.
³ Departments of Biostatistics.
⁴ Head and Neck Surgery.
⁵ Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston.
⁶ Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, USA.
⁷ Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston; Oncology Center, Hospital BP, A Beneficencia Portuguesa de São Paulo, São Paulo, Brazil.
⁸ Department of Medical Oncology and Therapeutics Research, City of Hope Cancer Center, Duarte.
⁹ Department of Radiation Oncology, Dana Farber Cancer Institute, Boston.
¹⁰ Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston; Division of Hematology and Oncology, University of California San Diego Moores Cancer Center, La Jolla.
¹¹ Department of Medical Oncology, Dana Farber Cancer Institute, Boston; Department of Head and Neck Oncology, Baptist Health South Florida, Coral Gables.
¹² Departments of Diagnostic Radiology.
¹³ Pathology, University of Texas MD Anderson Cancer Center, Houston, USA.
¹⁴ Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston. Electronic address: vpapadim@mdanderson.org.

PMID: 30596812
PMCID: PMC7360148
DOI: 10.1093/annonc/mdy549

Abstract

Background: The survival advantage of induction chemotherapy (IC) followed by locoregional treatment is controversial in locally advanced head and neck squamous cell carcinoma (LAHNSCC). We previously showed feasibility and safety of cetuximab-based IC (paclitaxel/carboplatin/cetuximab-PCC, and docetaxel/cisplatin/5-fluorouracil/cetuximab-C-TPF) followed by local therapy in LAHNSCC. The primary end point of this phase II clinical trial with randomization to PCC and C-TPF followed by combined local therapy in patients with LAHNSCC stratified by human papillomavirus (HPV) status and T-stage was 2-year progression-free survival (PFS) compared with historical control.

Patients and methods: Eligible patients were ≥18 years with squamous cell carcinoma of the oropharynx, oral cavity, nasopharynx, hypopharynx, or larynx with measurable stage IV (T0-4N2b-2c/3M0) and known HPV by p16 status. Stratification was by HPV and T-stage into one of the two risk groups: (i) low-risk: HPV-positive and T0-3 or HPV-negative and T0-2; (ii) intermediate/high-risk: HPV-positive and T4 or HPV-negative and T3-4. Patient reported outcomes were carried out.

Results: A total of 136 patients were randomized in the study, 68 to each arm. With a median follow up of 3.2 years, the 2-year PFS in the PCC arm was 89% in the overall, 96% in the low-risk and 67% in the intermediate/high-risk groups; in the C-TPF arm 2-year PFS was 88% in the overall, 88% in the low-risk and 89% in the intermediate/high-risk groups.

Conclusion: The observed 2-year PFS of PCC in the low-risk group and of C-TPF in the intermediate/high-risk group showed a 20% improvement compared with the historical control derived from RTOG-0129, therefore reaching the primary end point of the trial.

Keywords: C-TPF; LAHNSCC; PCC; cetuximab; induction chemotherapy.

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Figures

**Figure 1**
Kaplan–Meier curves for all patients for (A) progression-free survival and (B) overall survival.

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References

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[1] Hayes D.N., Van Waes C., Seiwert TY. Genetic landscape of human papillomavirus-associated head and neck cancer and comparison to tobacco-related tumors. J Clin Oncol. 2015;33(29):3227–3234. - PMC - PubMed

[2] Hayes D.N., Van Waes C., Seiwert TY. Genetic landscape of human papillomavirus-associated head and neck cancer and comparison to tobacco-related tumors. J Clin Oncol. 2015;33(29):3227–3234. - PMC - PubMed

[3] Pignon J.P., Bourhis J., Domenge C., Designé L. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet. 2000;355(9208):949–955. - PubMed

[4] Pignon J.P., Bourhis J., Domenge C., Designé L. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet. 2000;355(9208):949–955. - PubMed

[5] Pignon J.P., le Maitre A., Maillard E., Bourhis J. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17, 346 patients. Radiother Oncol. 2009;92(1):4–14. - PubMed

[6] Pignon J.P., le Maitre A., Maillard E., Bourhis J. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17, 346 patients. Radiother Oncol. 2009;92(1):4–14. - PubMed

[7] Ghi M.G., Paccagnella A., Ferrari D. Induction TPF followed by concomitant treatment versus concomitant treatment alone in locally advanced head and neck cancer. A phase II–III trial. Ann Oncol. 2017;28:2206–2212. - PubMed

[8] Ghi M.G., Paccagnella A., Ferrari D. Induction TPF followed by concomitant treatment versus concomitant treatment alone in locally advanced head and neck cancer. A phase II–III trial. Ann Oncol. 2017;28:2206–2212. - PubMed

[9] Cohen E.E.W., Karrison T.G., Kocherginsky M. Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer. J Clin Oncol. 2014;32(25):2735–2743. - PMC - PubMed

[10] Cohen E.E.W., Karrison T.G., Kocherginsky M. Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer. J Clin Oncol. 2014;32(25):2735–2743. - PMC - PubMed

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Weekly paclitaxel, carboplatin, cetuximab, and cetuximab, docetaxel, cisplatin, and fluorouracil, followed by local therapy in previously untreated, locally advanced head and neck squamous cell carcinoma

Affiliations

Weekly paclitaxel, carboplatin, cetuximab, and cetuximab, docetaxel, cisplatin, and fluorouracil, followed by local therapy in previously untreated, locally advanced head and neck squamous cell carcinoma

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Abstract

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