Less can sometimes be more.
In the phase 2 trial, 95% of patients with locally advanced oropharynx cancer and HPV remained progression free at 2 years following reduced-dose radiation therapy (50 Gy), compared with 96% of patients receiving standard-dose radiation therapy (60 Gy). Both groups avoided chemotherapy as well.
The results, published in the Journal of Clinical Oncology, suggest that postoperative radiation therapy at 50 Gy without chemotherapy was safe and effective in this intermediate-risk subset of patients, the authors concluded.
Although it’s hard for one trial to define standard of care, this study “may be an example of a practice-changing phase 2 [trial],” said lead author Robert L. Ferris, MD, PhD, director of the University of Pittsburgh Medical Center Hillman Cancer Center. “We and others have adopted 50 Gy without chemo as our adjuvant treatment for up to 4 positive nodes and 1 mm of extranodal extension.”
Treatment deintensification for patients with HPV and oropharynx cancer is an active area of investigation, but whether undergoing transoral surgery can allow intermediate-risk patients to receive a lower dose of adjuvant therapy remains uncertain.
Recent results from a phase 3 trial, presented during the plenary session at the 2021 annual meeting of the American Society for Radiation Oncology, showed that de-escalated adjuvant radiation therapy resulted in robust responses and lower toxicity as compared with standard care radiotherapy in patients with HPV and oropharyngeal squamous cell carcinoma.
The goal of the current ECON-ACRIN (E3311) trial was to prospectively assess the 2-year progression-free survival of transoral surgery and reduced adjuvant therapy in intermediate-risk patients with HPV and oropharynx cancer.
The phase 2 trial included 359 patients with HPV and oropharynx cancer who underwent surgery and were then assigned to one of four treatment groups based on individual risk factors for recurrence: low-risk patients under observation (arm A); intermediate-risk patients receiving low-dose radiation therapy (50 Gy, arm B) and those receiving standard-dose radiation (60 Gy, arm C) both without chemotherapy; and finally high-risk patients receiving chemotherapy in combination with high-dose radiation (arm D).
Among patients who underwent transoral surgery, 11% were assigned to arm A, 28% and 30% were randomly allocated to arms B and C, respectively, and 31% were assigned to arm D. For those who underwent transoral laser microsurgery, 11% were assigned to arm A, 32% and 24% were randomly allocated to arms B and C, respectively, and 34% were assigned to arm D.
Almost all patients (95%) in arm B remained progression free at 2 years after receiving reduced-dose radiation therapy. This rate of progression-free survival aligned with those observed in the other cohorts: 91% in high-risk patients receiving chemotherapy in combination with standard 66 Gy high-dose radiation, 96% in intermediate-risk patients in the 60 Gy standard-dose radiation arm, and 97% in the low-risk observation arm.
Although progression-free survival did not differ statistically between the arms (P = .90 for B vs. C; P = .30 for B vs. D; P = .30 for C vs. D), the authors urged caution when interpreting the results because the study was not powered to compare arms B and C directly.
Overall, these results show that “we could reduce radiation therapy and eliminate chemotherapy for 70% of patients,” Dr. Ferris said in an interview. Plus, “a small group of the lowest-risk [patients] did well with surgery alone.”
Regarding outcomes for quality of life (functional assessment of cancer therapy–head and neck) and swallowing (MD Anderson Dysphagia Index), patients reported a consistent decline in both during treatment. Patient scores, however, recovered to baseline levels in arms A-C and remained slightly lower after adjuvant therapy in arm D; however, it is unknown whether differences will emerge over a longer-term period.
Bhishamjit S. Chera, MD, an associate professor and radiation oncologist at the University of North Carolina at Chapel Hill, noted that reduced doses are not the current standard of care but it’s the “direction we’re headed.”
“I have started to use lower doses in selected patients” and other experts are offering it as well, said Dr. Chera, who was not involved in the research.
He also said that patients appear very interested in participating in lower-intensity therapy, judging by how rapidly accrual is for clinical trials of this nature.
However, caution is warranted.
“You have to be careful when you reduce intensity and there are different ways of doing it,” Dr. Chera said. “It’s not ready for community practice, and if it is offered to patients, it needs to be explained carefully with informed consent.”
The study was supported by the National Cancer Institute of the National Institutes of Health. Dr. Ferris has disclosed relationships Novasenta, Merck, Pfizer, EMD Serono, Numab, Macrogenics, Aduro Biotech, Sanofi, Zymeworks, Bristol-Myers Squibb, AstraZeneca/MedImmune, and Tesaro. Dr. Chera disclosed stock and other ownership interests in Naveris, and a consulting or advisory role with Naveris. He is a coinventor on a patent application regarding a method for measuring tumor-derived viral nucleic acids in blood samples, which is owned by the University of North Carolina at Chapel Hill and licensed to Naveris.
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