The addition of bevacizumab to the current standard of care of chemoradiation therapy is safe and feasible for the treatment of locally or regionally advanced nasopharyngeal cancer, according to data presented at the 2020 Multidisciplinary Head and Neck Cancers Symposium.1
“I’m pleased to report that nearly 70% of patients tolerated the addition of bevacizumab to both concurrent cisplatin and radiation therapy, as well as the adjuvant portion,” said Nancy Y. Lee, MD, FASTRO, Vice Chair of Radiation Oncology, Experimental Therapeutics; Service Chief of Head & Neck Radiation Oncology; and Proton Therapy Service Chief at Memorial Sloan Kettering Cancer Center, New York. “The low rate of distant metastasis was also striking, considering that almost 90% of patients had stage III or IV disease. This warrants further investigation.”
“The low rate of distant metastasis was also striking, considering that almost 90% of patients had stage III or IV disease.”— Nancy Y. Lee, MD, FASTRO
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Long-term results of the multicenter, phase II study showed no grade 4 hemorrhage or grade 5 adverse events after combining concurrent chemotherapy and radiation with bevacizumab. Moreover, despite the overwhelming majority of patients presenting with stage III or IV disease, the rate of distant metastasis was low, with just 20% of patients experiencing distant metastasis at 7 years.
As Dr. Lee reported, locoregionally advanced nasopharyngeal cancer is treated with concurrent cisplatin and radiation therapy, followed by adjuvant cisplatin and fluorouracil (5-FU) to achieve high rates of locoregional control, but distant metastasis remains an issue. Up to 30% of patients develop distant metastasis, which is the predominant cause of death, noted Dr. Lee.
The rationale for the addition of bevacizumab comes from elevated vascular endothelial growth factor (VEGF), which is associated with a poor prognosis in head and neck cancers and is overexpressed in approximately two-thirds of nasopharyngeal cancer. As Dr. Lee explained, the monoclonal antibody bevacizumab blocks VEGF-A; it has been shown to reduce the rate of distant metastasis and improve disease-free survival in patients with many solid tumors. Bevacizumab is currently approved by the U.S. Food and Drug Administration for multiple metastatic cancers, including lung, colon, and cervical.
For this study, Dr. Lee and colleagues enrolled patients with nasopharyngeal cancer between December 2006 and February 2009. All patients with World Health Organization stage I to IIb/III or stage IIB or greater disease were eligible, regardless of lymph node status. The investigators administered bevacizumab (15 mg/kg) and cisplatin (100 mg/m2) concurrently on days 1, 22, and 43 with intensity-modulated radiation therapy or three-dimensional conformal radiotherapy (to a total dose of 69.96 Gy over 33 fractions). This regimen was followed by adjuvant bevacizumab (15 mg/kg) and cisplatin (80 mg/m2) on day 1 and 5-FU (1,000 mg/m2/d) on days 1 through 4 for three cycles.
The study’s primary endpoint was grade 4 hemorrhage or grade 5 adverse events in the first year. Secondary endpoints included local-regional progression-free rates, distant metastasis–free rates, progression-free survival, and overall survival.
‘Unheard of’ Rate of Distant Metastasis
As Dr. Lee reported, 44 of 46 patients enrolled were evaluated. Patients were predominantly male (65.9%) and Asian (52.3%), with a median age of 48.5 years. Although this cohort had a good performance status, said Dr. Lee, the overwhelming majority had advanced disease: approximately 90% of patients had node-positive disease, and 88.6% were classified as having stage III or IV disease.
Results of the study showed that 68.2% of patients tolerated the addition of bevacizumab to both concurrent cisplatin and radiation as well as adjuvant cisplatin and 5-FU chemotherapy. “This regimen was tolerable and consistent with what is seen without bevacizumab,” said Dr. Lee, who reported no grade 4 hemorrhage or grade 5 events and no deaths within 30 days of completion of protocol treatments.
Notably, the regimen was also effective in controlling distant metastases. The 2-year distant metastasis–free rate of nearly 90% is unheard of for this group of patients, according to Dr. Lee, and 5- and 7-year distant metastasis–free rates were both 79.5%.
The reported grade 3 or 4 complication rates increased from 22.7% to 36.4% from the initial report, including two additional cases of dysphagia and some hearing issues, which may be attributed to cisplatin, noted Dr. Lee. However, just 3.4% of patients required a feeding tube at 4 years. “Not seeing excessive feeding tubes is very encouraging,” said Dr. Lee, who noted that survival data were promising as well. The 5- and 7-year progression-free survival rates were 61.2% and 56.3%, respectively, and 5- and 7-year overall survival rates were 79.5% and 69.7%, respectively, Dr. Lee reported.
When asked how she is currently treating locally advanced nasopharyngel carcinoma in her practice, Dr. Lee explained, “Every patient who comes to our institution is put on HN001, a phase III trial for individualized treatment of nasopharyngeal carcinoma based on the Epstein-Barr virus biomarker, but not everyone can go on trial. If a patient is deemed an induction candidate, we will give the patient gemcitabine/cisplatin; we have found it to be a little more tolerable than TPF [docetaxel, cisplatin, and 5-FU].”
She continued, “In general, our center is still treating patients with concurrent chemoradiation followed by adjuvant chemotherapy. There will be data out this year showing that concurrent chemoradiation in this group of patients is not enough. Either you give induction, or you give adjuvant chemotherapy in addition to concurrent chemoradiation. You just cannot give concurrent chemoradiation alone.”
DISCLOSURE: Dr. Lee has served as a consultant or advisor to Merck, Merck/Serono, Pfizer, and Sanofi; has received research funding from AstraZeneca; and has received institutional research funding from Pfizer. Dr. Haddad has served as a consultant or advisor to AstraZeneca, Bristol-Myers Squibb, Celgene, Eisai, Genentech, GSK, Immunomic Therapeutics, Loxo, Merck, and Pfizer; and has received institutional research funding from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Genentech, Kura, Merck, Pfizer, and VentiRx.
1. Lee N, Harris J, Pfister DG, et al: Long-term update of a phase II study of concurrent chemoradiotherapy using radiation + bevacizumab for locally or regionally advanced nasopharyngeal cancer: RTOG 0615. 2020 Multidisciplinary Head and Neck Cancers Symposium. Abstract 10. Presented February 28, 2020.