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Cisplatin with radiation ‘standard of care’ for HPV-related oral cancers
Chemoradiotherapy produced superior survival outcomes compared with radiation and cetuximab in a cohort of patients with HPV-associated oropharyngeal cancer, according to randomized, phase 3 trial results presented at the American Society for Radiation Oncology Annual Meeting.
“We’ve now established that high-dose cisplatin chemotherapy — in combination with radiation — is the standard of care for HPV-related oral cancers,” Andy Trotti, MD, a radiation oncologist at Moffitt Cancer Center and co-lead investigator of the NRG Oncology/RTOG 1016 study, said in a press release. “Prior to this study, there were no definitive, state-of-the-art trials in this specific cancer population.”
Cetuximab (Erbitux, Eli Lilly), an EGFR inhibitor approved in the United States for treatment of head and neck cancer, plus radiotherapy has been proposed as a less-toxic alternative to cisplatin plus radiotherapy. The treatments also were evaluated in study results presented at European Society for Medical Oncology Congress.
Trotti and colleagues randomly assigned 805 patients (median age, 58 years; 90% men) with locoregionally advanced HPV-related oropharynx cancer to two cycles of cisplatin 100 mg/m2 every 3 weeks plus radiation, or weekly cetuximab and the same radiation regimen.
“We had hypothesized that survival with cetuximab might be very close, within 5%, to that of cisplatin,” Trotti said in a press release. “But that was not the case.”
The cisplatin regimen appeared associated with improved OS compared with cetuximab (HR = 1.45; 95% CI, 1.03-2.05), according to an interim data analysis. A similar outcome was reported for 5-year PFS, with an estimated 78.4% of patients in the cisplatin group reaching this endpoint, compared with 67.3% of those in the cetuximab group (HR = 1.72; 95% CI, 1.29-2.29).
The cisplatin group demonstrated lower estimated 5-year rates of local-regional failure (9.9% vs. 17.3%) and distant metastases (8.6% vs. 11.7%) and a substantially higher 5-year survival rate (84.6% vs. 77.9%) than the cetuximab group.
Rates of grade 3 to grade 5 adverse events were higher among the cisplatin group than the cetuximab group (82% vs. 77%). Researchers suggested that the novel T-score reporting system for adverse events may paint a clearer picture of the toxicity profile of the two regimens. Using this system, cisplatin demonstrated a 40% increase in incidence of high-grade events.
A variety of adverse events were associated with cisplatin, including anemia, hearing loss, nausea, vomiting, neutropenia and kidney injuries. Cetuximab yielded a higher rate of rash. Long-term dysphagia rates were 4% for cisplatin and 6% for cetuximab.
Trotti said cetuximab may still be considered a viable treatment option for patients who cannot tolerate cisplatin, including those with significant hearing loss or severe diabetes-related neuropathy. – by Rob Volansky
Reference:
Trotti A, et al. Abstract LBA-4. Presented at: American Society for Radiation Oncology Annual Meeting; Oct. 21-24, 2018; San Antonio.
Disclosure: HemOnc Today could not confirm Trotti’s relevant financial disclosures at the time of reporting.
Perspective
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The RTOG 1016 trial reinforced two incredibly important lessons.
First, we learned that — despite many head and neck cancer experts having a strong suspicion that de-intensifying therapy for patients with HPV-associated oropharynx cancer would be safe, we must continue to study these regimens on trials and not adopt them in routine clinical practice before being properly tested.
In this case, de-escalation led to increased recurrences, and this has served as a vital wake-up call to proceed with caution with these very curable patients.
Second, moving forward we must be smarter about our clinical trial design. We now know that not all HPV-associated oropharynx cancers are created equal, and there are clear subgroups of lower-risk and higher-risk patient populations. These groupings, which have been incorporated into the eighth edition of the American Joint Committee on Cancer (AJCC) staging system, were not well-appreciated at the initiation of this study. Properly selecting subpopulations of patients for de-intensification regimens will be vital to the success of this approach.
I am hopeful that NRG-HN002 and NRG-HN005 — second- and third-generation HPV-associated oropharynx cancer de-escalation trials that are limited almost exclusively to patients with AJCC 8 stage I HPV-associated oropharynx cancer who have had minimal tobacco exposure — will identify a successful de-escalation strategy in the properly selected very low-risk subgroup. The same principle applies to intensification trials in high-risk patient populations.
Ensuring we do not dilute out a potential benefit of novel therapies by including lower-risk patients will be vital to future trials being able to answer important questions in subgroups of interest. Ultimately, novel tissue and/or blood-based biomarkers are needed to substantially improve our ability to properly bin patients in distinct subgroups and include more homogeneous patient populations in our clinical trials.
Perspective
Back to TopI believe 1016 changes practice immediately. It was unknown until the release of the NCI press release for this study a few months ago that platinum with radiation would give a higher overall survival at 5 years than radiation and cetuximab. Based on this study, we now know that to be true. It gives very important information to practitioners around the world that if a patient is able to receive cisplatin with radiation, it is the preferred regimen. That new information was borne out by this trial. Very similar to trial 1016 was a study presented at ESMO. It was the same trial design, a bit smaller with less power than the 1016 trial, but it showed, in all major parameters, higher overall survival and local control with the platinum-radiation combination versus cetuximab and radiation. So, on the same day, essentially, on both sides of the Atlantic, we have powerful corroboration from two major trials showing this impact.
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