Investigators of a new phase II study reported that favorable-risk oropharyngeal squamous cell carcinoma testing positive for human papillomavirus or p16 can be treated successfully using substantially decreased chemoradiotherapy doses.
Bhishamjit S. Chera, MD
Investigators of a new, prospective, multi-institutional, phase II study reported that favorable-risk oropharyngeal squamous cell carcinoma (OPSCC) positive for human papillomavirus (HPV) or p16 can be treated successfully with fewer side effects using substantially decreased chemoradiotherapy (CRT) doses. The study findings were presented at the 2015 American Society for Radiation Oncology Annual Meeting and published online in theInternational Journal of Radiation Oncology, Biology, Physics.1
The study builds on previous research that showed that patients with HPV- or p16-associated OPSCCs responded much better to radiation and chemotherapy than patients with HPV- or p16-negative disease.2In addition to having favorable-risk OPSCCs, all study patients (n=43) had a minimal smoking history.
Treatment was limited to 60 Gy intensity-modulated radiotherapy with concurrent weekly 30 mg/m2intravenous cisplatinum for 6 weeks. Historically, standard treatment of OPSCCs includes 70 Gy intensity-modulated radiotherapy once weekly for 7 weeks, three high doses of cisplatinum, and, in some cases, post-treatment surgery.2,3Although this standard regimen has a high cure rate (>90%), it has been associated with numerous side effects and long-term complications.3
“We decided on the lower dosages based on our experiences with anal cancer,” said the study’s first author and principal investigator Bhishamjit S. Chera, MD, UNC Lineberger member and associate professor in the Department of Radiation Oncology at the University of North Carolina (UNC) School of Medicine, in an interview withTargeted Oncology. “Squamous cell carcinoma of the anal canal is also related to HPV and standardly treated with radiation and chemotherapy, with radiation doses ranging from 50 Gy to 60 Gy. We hypothesized that HPV-associated oropharyngeal cancer would be as radiosensitive as HPV-associated anal cancer, leading us to select the 60 Gy dosage.”
In the study, the de-intensified CRT regimen achieved an 86% pathologic complete response rate. Of its 43 patients, 37 (86%) achieved a pathologic complete response with the de-intensified CRT regimen. Disease in the remaining 6 patients was limited to microscopic foci of residual cancer, with one at the primary site and five in the lymph nodes. Pathologic complete response, which was the study’s primary endpoint, was assessed for through a biopsy of the primary tumor site and a limited neck surgery to remove any pretreatment cancerous lymph node regions. After a median follow-up of 20.7 months (range, 6-36 months), all patients were alive with no evidence of disease. “These results suggest that we are probably over-treating these patients with the standard radiation and chemotherapy regimens,” said Chera.
The study also had several secondary endpoint measures, including physician-reported toxicity, patient-reported symptoms, quality of life, and penetration aspiration scale scores for modified barium-swallow studies. Overall, the investigators observed fewer acute side effects with the de-intensified regimen.
“Most notably, patients experienced fewer hematological toxicities and less swallowing side effects,” said Chera. “With standard radiation and chemotherapy, approximately 80% of patients require a feeding tube to make it through treatment and 10% need a permanent feeding tube, whereas in our study of de-intensified radiation and chemotherapy, only 40% needed a feeding tube and none were permanent.”
Chera believes the study patients will have excellent long-term cancer control but notes that further follow-up is needed. Although other clinical trials are evaluating different de-intensified regimens, Chera noted that his study is unique because both radiation and chemotherapy were substantially reduced and neither induction chemotherapy nor definitive surgery were performed.
Chera toldTargeted Oncologythat additional follow-up studies are underway or planned, including one that eliminates chemotherapy altogether for select patients. “We are currently conducting a follow-up, second-generation, phase II study at UNC with our colleagues in the University of Florida, which will soon be close to accrual and in which the lowest stage patients are only getting 60 Gy intensity-modulated radiotherapy, without concurrent chemotherapy,” he said. “In addition, patients with moderate and remote smoking histories are eligible and biopsy with limited neck surgery is not mandated, as all patients are assessed with a posttreatment positron emission tomography/computed tomography scan at 12 weeks to guide biopsy/surgical evaluation.”
A third-generation study is also planned. “This study will use cancer genomics to help us identify more patients in whom we can safely de-intensify treatment,” said Chera.
Chera’s current study was funded by the UNC School of Medicine, Department of Radiation Oncology, and the University of Florida School of Medicine, Department of Radiation Oncology.