Standard Regimen Remains Superior in HPV-positive Oropharyngeal Carcinoma

Despite associated toxicities, cisplatin chemotherapy induced superior efficacy compared with a new alternative among patients with HPV-positive oropharyngeal carcinoma.
 
BY Kristie L. Kahl
PUBLISHED November 27, 2018
The standard of care for eligible patients with HPV-positive oropharyngeal carcinoma remains, as a new alternative used in conjunction with radiotherapy failed to demonstrate superior survival outcomes, according to results from the phase 3 RTOG 1016 trial published in The Lancet.

Erbitux (cetuximab), an EGFR inhibitor that is presumably less toxic than cisplatin chemotherapy – known for lasting side effects such as hearing loss and kidney damage – was not as effective in prolonging survival and preventing disease progression in HPV-positive oropharyngeal carcinoma, a type of cancer that forms in the tonsils or the base of the tongue.

“Although one prior study suggested that cetuximab may provide survival benefits of similar magnitude as cisplatin when combined with radiation but with fewer long-term side effects, these two regimens have not been compared head to head in such a large study before,” study author Quynh-Thu Le, M.D., professor and chair of radiation oncology at Stanford University explained in a statement.

“The result of our study showed that this is not the case,” she added. “Unfortunately, this means we are back to square one. We have to figure out a better way to reduce toxicity for these patients.”

While HPV-positive oropharyngeal carcinoma can be highly treatable with radiation and chemotherapy, it is particularly important to minimize long-term side effects in these patients, as they are typically diagnosed at a relatively young age.

Therefore, Le and colleagues conducted the randomized, prospective multicenter phase 3 RTOG 1016 trial to determine whether Erbitux and cisplatin – both in combination with radiotherapy – were equally effective at treating HPV-positive oropharyngeal cancer.

From June 2011 to July 2014, across 182 health care centers in the US and Canada, 849 patients were randomized to receive either:
  • a loading dose of 400 mg/m2 of Erbitux five to seven days before radiotherapy initiation, followed by 250 mg/m2 of Erbitux weekly for seven doses (399 eligible patients), or
  • 100 mg/m2 of cisplatin on days one and 22 of radiotherapy (406 eligible patients).
All patients received accelerated intensity-modulated radiotherapy delivered at 70 Gy in 35 fractions over six weeks at six fractions per week.

After a median follow-up of 4.5 years, Erbitux plus radiotherapy failed to meet the non-inferiority criteria for overall survival: estimated five-year overall survival was 77.9 percent in the Erbitux group compared with 84.6 percent in the cisplatin arm.

Similarly, five-year progression-free survival was significantly lower (67.3 percent vs. 73.8 percent) and locoregional failure at five years was significantly higher (17.3 percent vs. 9.9 percent) among the Erbitux arm compared with the cisplatin therapy group.

Meanwhile, the rate of acute moderate to severe toxicity (77.4 percent vs. 81.7 percent) and late moderate to severe toxicity (16.5 percent vs. 20.4 percent) were similar between arms.

“Unfortunately, our assumption that cetuximab would be less toxic but confer similar survival advantages did not pan out,” Le said. “Cisplatin should still be the standard of care for most of these patients while we investigate other potentially less toxic treatments, such as immunotherapy.”
 
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