De-escalated IMRT regimen shows promise in HPV-associated oropharyngeal carcinoma
De-escalated intensity-modulated radiotherapy plus concurrent cisplatin satisfied criteria for further study among patients with HPV-related oropharyngeal squamous cell carcinoma, according to phase 2 study results.
The reduced-dose radiation plus cisplatin regimen met the threshold for disease control and quality of life compared with standard-of-care treatment, whereas an accelerated radiation regimen without cisplatin did not, according to the findings, published in Journal of Clinical Oncology.
“Many patients with HPV-related oropharyngeal squamous cell carcinoma tend to be younger, and because they are nonsmokers or previous light smokers, they also tend to live longer,” Sue S. Yom, MD, PhD, professor in the department of radiation oncology and otolaryngology-head and neck surgery at University of California, San Francisco, told Healio. “As a result, many people are worried about the long-term side effects of high-dose radiation in these patients. For many years, there have been proponents within the NRG Oncology Group wanting to test the proposition that we could reduce the radiation doses safely in these patients. Our study was designed to give birth to the components for future study.”
Yom and colleagues sought to identify a suitable de-escalated treatment regimen for a prospective phase 2 or phase 3 randomized controlled trial.
They randomly assigned 306 patients (median age, 59 years; 84% men) with p16-positive oropharyngeal squamous cell carcinoma and a smoking history of 10 years or less to either 60 Gy IMRT for 6 weeks plus concurrent cisplatin (n = 157) or an accelerated regimen of 60 Gy IMRT alone for 5 weeks (n = 149). More than half of patients had T2 or T3 disease (62.4%), N2 disease (75.5%) and tonsil as the primary cancer site (52.6%).
Researchers considered treatment to be worthy of phase 3 study if it conferred a 2-year PFS rate higher than the historical control rate of 85% and a 1-year mean composite score of 60 or greater according to the MD Anderson Dysphagia Inventory (MDADI).
Results showed a 2-year PFS rate of 90.5% with the combination regimen, which statistically superior to the 85% historical rate (P = .04), compared with a statistically nonsignificant 87.6% with IMRT alone (HR = 0.67; 95% CI, 0.36-1.24).
The combination and IMRT-only groups had similar rates of 2-year OS (96.7% vs. 97.3%; HR = 0.95; 95% CI, 0.31-2.95).
One-year mean MDADI scores were 85.3 for the combination regimen and 81.76 with IMRT alone.
“We have high confidence that 60 Gy with concurrent cisplatin produces an outcome similar to that of the standard 70 Gy with cisplatin that was used in a prior clinical trial,” Yom said. “We believe that this arm, comprised of 60 Gy with cisplatin, is the arm that should move forward to further testing in clinical trials.”
Grade 3 to grade 4 acute toxicities appeared more common with the combination regimen (79.6% vs. 52.4%; P < .001).
“However, we showed that the reduced dose resulted in excellent swallowing-related quality of life. We have also established that it is feasible within a national cooperative group clinical trial to select certain patients for unilateral radiation therapy and use PET/CT scan between 12 weeks and 14 weeks after radiation ends to evaluate response,” Yom said.
Based upon these findings, researchers initiated the NRG HN005 trial comparing 70 Gy IMRT plus cisplatin with 60 Gy IMRT plus either cisplatin or the anti-PD-1 antibody nivolumab (Opdivo, Bristol Myers Squibb).
“We are continuing to clarify the relative roles of chemotherapy and radiation therapy in this disease, as well as clarify the risks and benefits of this type of nonsurgical program compared with surgery,” Yom said. “We learned quite a bit about quality of life from this study, which we are taking forward into future trials. We also plan to continue to look at secondary analyses of the biology and physics of this study, which will help us in designing future trials.”
Although the current study requires further investigation and confirmation, there were some potentially hypothesis-generating observations, Yom added.
“The radiation-only arm did not appear to maintain as much efficacy as the chemoradiation arm for higher-stage disease, but there were so few patients with disease relapse that we do not know this with certainty,” Yom said. “In addition, there was no apparent effect on distant metastases from use of concurrent chemotherapy in this population, although with the overall rates being so small, it is hard to tell. The reduced dose of 60 Gy, whether given with chemotherapy or not, produced good results in most patients, but only the chemoradiation arm could be confidently predicted to produce statistically similar results as 70 Gy with cisplatin.”
The wide landscape of seemingly promising treatment options for HPV-related oropharyngeal squamous cell carcinoma somewhat mirrors that for low-risk prostate cancer and makes the decision-making process incredibly confusing and difficult, Anupama Chundury, MD, and Sung Kim, MD, radiation oncologists at Rutgers Cancer Institute of New Jersey at University Hospital, wrote in an accompanying editorial.
“Until the results of NRG HN005 are published, it goes without saying that we strongly encourage caregivers to put eligible patients on this protocol if at all possible,” they wrote.
References:
Chundury A and Kim S. J Clin Oncol. 2021;doi:10.1200/JCO.21.00017.
Yom SS, et al. J Clin Oncol. 2021;doi:10.1200/JCO.20.03128.
For more information:
Sue S. Yom, MD, PhD, can be reached at University of California, San Francisco, 1825 4th St., Suite L1101, San Francisco, CA 94158; email: sue.yom@ucsf.edu.
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