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Cetuximab Regimen Inferior To Cisplatin For HPV-Positive Oropharyngeal Carcinoma

Cisplatin plus radiation offers better survival outcomes and no worse toxicity than cetuximab plus radiation for patients with HPV-positive oropharyngeal carcinoma
19 Nov 2018
Anticancer Agents;  Head and Neck Cancers;  Radiation Oncology

Author:  By Lynda Williams, Senior medwireNews Reporter

medwireNews: Cetuximab results in poorer overall survival (OS) than cisplatin for patients with human papillomavirus (HPV)-positive oropharyngeal carcinoma without improvement in toxicity, suggest findings from two studies published in The Lancet

“Cisplatin should be used as the radiosensitiser of choice in all eligible patients with advanced HPV-positive oropharyngeal squamous cell carcinoma”, the authors of a linked comment summarise.

“This recommendation is pertinent as there is emerging evidence showing a substantial increase in HPV-positive oropharyngeal squamous cell carcinoma in older patient groups (>70 years)”, say Johannes Christiaan Oosthuizen, from Ipswich Hospital in Queensland, Australia, and Jaime Doody, from Harvard Medical School in Boston, Massachusetts, USA.

The findings of the De-ESCALaTE HPV trial of European patients with low-risk, advanced squamous cell carcinoma were previously reported at the ESMO 2018 Congress in Munich, Germany, by Hisham Mehanna, from the University of Birmingham in the UK. The primary endpoint of the study was toxicity and the all-grade rates of early and late adverse events were comparable for cetuximab and cisplatin, albeit with a higher rate of serious adverse events with cisplatin. But the secondary endpoint of overall survival significantly favoured cisplatin plus radiotherapy over cetuximab and radiotherapy. 

The second RTOG 1016 trial included US and Canadian patients with HPV-positive T1–T2, N2a–N3 M0 or T3-T4, N0-N3 M0 disease, all of whom were scheduled to receive 70 Gy accelerated intensity-modulated radiotherapy given in 35 fractions over 6 weeks. 

The patients were randomly assigned to receive a loading dose of cetuximab 400 mg/m2 5–7 days before radiation followed by seven courses of weekly cetuximab 250 mg/m2, or cisplatin 100 mg/m2 given on days 1 and 22 of radiotherapy. 

Over a median of 4.5 years of follow-up, 59% of patients given cetuximab and 41% of those given cisplatin died, giving a significant hazard ratio (HR) for death of 1.45. 

Thus, radiotherapy plus cetuximab was not demonstrated to be noninferior to radiotherapy plus cisplatin for the primary endpoint of OS, report Maura Gillison, from the University of Texas MD Anderson Cancer Center in Houston, USA, and co-investigators. 

Progression-free survival (PFS) was also significantly poorer with cetuximab versus cisplatin (HR=1.72), and the estimated 5-year rates of both OS and PFS were significantly lower in the cetuximab arm, at 77.9% versus 84.6%, and 67.3% versus 78.4%, respectively. 

Furthermore, the cetuximab regimen was not associated with reduced toxicity compared with cisplatin, with comparable rates of both acute moderate-to-severe toxicity (77.4 vs 81.7%) and late moderate-to-severe toxicity (16.5 vs 20.4%). 

“Radiotherapy plus cisplatin is the standard of care for eligible patients with HPV-positive oropharyngeal carcinoma”, the RTOG 1016 investigators therefore conclude.

Discussing the findings, the commentators emphasize that these two “landmark” studies’ different designs and primary outcomes – reflecting regional differences in drug approvals and practices – are “complementary and serve to offset any substantial limitations of either study in isolation.”

They add: “These results also serve as a timely reminder that although HPV-positive oropharyngeal squamous cell carcinoma has an excellent prognosis with existing well established treatment protocols, treatment de-intensification strategies should only be evaluated within the confines of well designed clinical trials.” 

References 

Oosthuizen JC, Doody J. De-intensified treatment in human papillomavirus-positive oropharyngeal cancer. Lancet; Advance online publication 15 November 2018. http://dx.doi.org/10.1016/S0140-6736(18)32930-1 

Gillison ML, Trotti AM, Harris J, et al. Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicenter, non-inferiority trial. Lancet; Advance online publication 15 November 2018. http://dx.doi.org/10.1016/S0140-6736(18)32779-X 

Mehanna H, Robinson M, Hartley A, et al. Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial. Lancet; Advance online publication 15 November 2018. http://dx.doi.org/10.1016/ S0140-6736(18)32752-1

Last update: 19 Nov 2018

medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group

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