Cisplatin Superior To Cetuximab For Low-Risk, HPV-Positive Oropharyngeal Cancer

For patients undergoing radiotherapy for low-risk, human papillomavirus-positive oropharyngeal cancer, cisplatin should remain the standard of care

medwireNews: Cisplatin plus radical radiotherapy should remain the standard of care for low-risk patients with human papillomavirus (HPV)-positive oropharyngeal cancer, suggests research presented at the ESMO 2018 Congress in Munich, Germany. 

The De-ESCALaTE HPV trial results for 334 patients with HPV-positive, low-risk disease, defined as stage III–IVa without distant metastases, were reported by Hisham Mehanna, from the University of Birmingham in the UK. 

The primary endpoint of the trial was to compare toxicity of cisplatin 100 mg/m2 on days 1, 22 and 43 of treatment versus cetuximab 400 mg loading dose followed by weekly 250 mg doses. All patients were also assigned to receive 70 Gy of radiation in 35 fractions over 7 weeks. 

All-grade adverse events occurred at a similar rate in the cisplatin and cetuximab arms (29.15 vs 30.05%) and this was true for both acute (19.96 vs 20.35%) and late (9.44 vs 9.87%) side effects. 

Similarly, the overall rate of grade 3–5 adverse events was comparable in the cisplatin and cetuximab groups (4.81 vs 4.82%) and the same pattern was observed for both acute (4.43 vs 4.35%) and late (0.41 vs 0.48%) severe events. 

But cisplatin was associated with a significantly higher rate of serious adverse events than cetuximab, affecting 1.00% versus 0.58% of patients, despite global health status and dysphagia scores indicating similar quality of life between the two arms. 

Of concern, however, the secondary endpoint of overall survival (OS) significantly differed between the cisplatin and cetuximab treatment arms, with 2-year rates of 97.5% and 89.4%, respectively. This gave a hazard ratio (HR) for survival of 4.99 in favour of cisplatin, rising to 5.94 after adjustment for risk factors. 

Indeed, the number needed to treat with cetuximab versus cisplatin to cause harm was just 12, said Hisham Mehanna. 

The OS findings may have reflected a significant difference in recurrence between the two arms, with a 2-year rate of 6.0% with cisplatin versus 16.1% for cetuximab, giving a HR of 3.39. Rates of both locoregional recurrence (3.0 vs 12.0%) and distant recurrence (3.0 vs 9.0%) significantly favoured use of cisplatin. 

And sensitivity analyses demonstrated a significant 2-year OS benefit with cisplatin over cetuximab even when including only the “very low risk” patients with TNM stage I/II disease (98.4 vs 93.2%, HR=4.27). 

Hisham Mehanna therefore concluded that “cisplatin remains the standard of care in HPV-positive low-risk patients when it can be given to them.” 

He emphasized that the De-ESCALaTE trial showed a role for cisplatin in both locoregional control and distant metastases and therefore he “advises caution when using de-escalation treatments that reduce systemic chemotherapy”, such as regimens of radiation alone or with surgery. 

Hisham Mehanna added: “There’s a salutary lesson – changes in the standard of care should only be done on the basis of high-level, phase III comparative evidence, even as in our case, [with] treatments [that] have been approved by regulatory bodies.” 

 

Reference 

Mehanna H, Kong A, Hartley A, et al. Cetuximab versus cisplatin in patients with HPV-positive, low risk oropharyngeal cancer, receiving radical radiotherapy . ESMO 2018 Congress; Munich, Germany, 19–23 October (LBA9_PR).

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