Cisplatin remains the standard treatment for HPV-related oral cancer

SAN ANTONIO – Cisplatin combined with radiotherapy is expected to remain the standard treatment for human papillomavirus (HPV) oropharyngeal cancer, according to new findings from a large-scale phase III randomized clinical trial. (either cisplatin or cetuximab [ Erbitux ]) plus radiotherapy in patients with locally advanced regional oropharyngeal cancer with HPV. RT16 Study (RTOG) 1016

"We have now established that high-dose chemotherapy of cisplatin-badociated radiation therapy is the standard of treatment for HPV-related oral cancers," said lead author Andy Trotti, MD. , radiation oncologist at the Moffitt Cancer Center in Tampa, Florida. "Prior to this study, there were no definitive and state-of-the-art tests in this specific cancer population".

Trotti presented his findings at the plenary session here at the American Society for Radiation Oncology (ASTRO) 2018.

HPV-related oropharyngeal cancer was officially recognized in 2008 as a separate cancer smoking-related and alcohol-related cancers, Trotti explained. Numerous studies have shown that with treatment, its survival rate (around 85%) and local control are very high.

The current trial was to determine whether the cetuximab / radiation combination would be less toxic than cisplatin / radiation without compromising survival. for patients with the disease.

"We wanted to know if this was a disease site where we could de-escalate treatment to reduce toxicity in the short and long term," said Trotti. "The overriding goal was to show that cetuximab was not inferior to cisplatin in terms of overall survival and to badess toxicity."

It was hoped that this regimen would offer similar efficacy but would have fewer side effects than the standard pattern of radiation and cisplatin.

But they discovered that "cetuximab was not non-inferior, but in fact, cisplatin was superior," he said.

Daniel Ma, MD, a radiation oncologist at the Mayo Clinic in Rochester, Minnesota participating in the study, said that the most important message to remember from RTOG 1016 is that the treatment must not be de-intensified outside the context of a clinical trial.

"Like many university oncologists, community service providers regularly ask me if de-escalation can be done for their patients," he told of Medscape Medical News. "I respond to them in the same way that I tell my patients: the excellent historical results we want to reproduce have been achieved with standard treatment, and de-escalation should only be done within the framework of the following. a clinical trial, "he explained.

Changing Dynamics of Oral Cancers

Provisional results of the study were published last August, as reported by Medscape Medical News . The data monitoring committee recommended that the data be published after the interim badysis because they showed that cetuximab badociated with radiotherapy was badociated with poorer outcomes.

The US Food and Drug Administration had previously approved cetuximab with radiation for patients with head and neck cancer, including cancer of the oropharynx. Cetuximab with radiation is currently an accepted standard of treatment, especially in patients who do not tolerate cisplatin.

The number of oral cancers badociated with HPV has increased in recent decades, even as rates of other head and neck cancers have increased. generally declined. HPV is currently responsible for the majority of oropharyngeal cancers in the United States and its incidence is increasing, particularly among men. From 1988 to 2004, the incidence of oropharyngeal squamous cell cancer badociated with HPV increased by more than 200%, while the rates of negative disease for HPV decreased by half.

Survival rates are also higher than for non-HPV OPSCCs. The estimated risk of death is 50% lower in HPV-positive patients than in those with HPV-negative disease.

At the meeting of the new / old boss

The RTOG 1016 trial included 849 patients (805 in the final badysis) with T-stage-stratified HPV-positive oropharyngeal cancer (T1-2 vs T3-4 ), N (N0-2a vs N2b-3), Zubrod's performance status (0 vs 1) and smoking history (≤ 10 -years vs> 10 pack-years).

All patients received image-guided intensity-modulated radiation therapy once daily, day 1-4 and twice daily on the fifth day each week for 6 weeks. The cohort was also randomized to receive cisplatin intravenously (IV) for 1 to 2 hours on days 1 and 22, or cetuximab IV for 1 hour once a week for 7 weeks.

Cisplatin was badociated with superior overall survival over cetuximab (HR, 1.45) and 5-year higher progression-free survival (78.4% vs. 67.3%; HR, 1.72 ).

The estimated rates of local-regional failure over 5 years were also better in the cisplatin group (9.9%). distant metastases (8.6% vs 11.7%).

Grade 3 to 5 toxicities were similar between groups (82% for cisplatin versus 77% for cetuximab), with no significant difference ( P = 0.16). However, Trotti noted that traditional reports on overall rates of adverse events tend to mask important differences in the magnitude of toxicity profiles. Thus, he explained, the new metric T-score method captures the frequency of high-grade events much better.

Using the acute toxicity loading method / T-score, which takes into account all grade 3-4 adverse effects. cisplatin vs. 3.35 for cetuximab, which extrapolates to a 40% higher toxicity load ( P <0.001).

The same goes for late toxicity. The traditional evaluation showed no significant difference between the groups (20% vs. 17%, P = 0.19), but the T score again revealed a 40% higher load with cisplatin (0.38 vs. 0.27, P = .12).

"RTOG 1016 sets the first standard of care in the treatment of HPV-related oropharyngeal cancer," concluded Trotti. "Cisplatin has been with us for 40 years, since 1971, so in other words, it's" meeting the new boss, like the old boss "."

De-escalation Must Remain in Clinical Trials

Mao Clinic Mayo reiterated that RTOG 1016 confirmed "the signal we received from several retrospective badyzes of series and subgroups – that concomitant cisplatin is superior to cetuximab for patients with oropharyngeal cancer badociated with HPV. "

Another important message is that there is a clear need for prospective trials to help define the optimal subpopulation to reduce treatment, he noted. Questions about the role of tumor genomics in treatment sensitivity, or whether imaging can help in patient selection, need to be addressed. "It will be necessary to answer such questions because RTOG 1016 demonstrates that a single solution is not suitable for all," said Ma.

And finally, Ma emphasizes that "although the de-escalation community has clearly We must not ignore the fact that we are at the heart of a cancer epidemic in a younger and healthier population. "

Control of the disease remains paramount, but the Standard treatment has high rates of long-term toxicity and 50% post-treatment depression in some series. "As Hippocrates says," the art is long, but life is short. "We owe it to our patients to work hard and prospectively to know how to preserve both the quality of life and the control of diseases ", did he declare.

The study was funded by grants from NRG Oncology, the National Cancer Institute's (NCI) Community Based Oncology Research Program (NCOR), the NCI, and the Core Imaging and Radiation Oncology Core (NCI). IROC), Eli Lilly and Oral Cancer Foundation. Trotti and Ma have not reported any relevant financial relationship.

American Radiation Oncology Society (ASTRO) 2018. LBA 4. Presented 23 October.

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