Weekly cisplatin a potential new standard for HNSCC
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Weekly cisplatin appeared noninferior to an every-3-weeks dose as part of chemoradiotherapy regimen for certain patients with head and neck squamous cell carcinoma, according to study results presented during the ASCO20 Virtual Scientific Program.
Chemoradiotherapy with weekly cisplatin also exhibited a favorable toxicity profile and should be considered the new standard of care for patients with postoperative, high-risk locally advanced HNSCC, researchers concluded.
Weekly cisplatin appeared noninferior to an every-3-weeks dose as part of chemoradiotherapy regimen for certain patients with head and neck squamous cell carcinoma.
“This trial met its primary endpoint of noninferiority OS,” Naomi Kiyota, MD, PhD, clinical researcher in the department of medical oncology and hematology at Kobe University Hospital in Japan, said during a presentation. “This study is the first to show that weekly [cisplatin] is noninferior to 3-weekly [cisplatin] in postoperative high-risk patients with squamous cell carcinoma of the head and neck.”
The standard treatment regimen for postoperative high-risk patients with locally advanced HNSCC is chemoradiotherapy consisting of cisplatin dosed at 100 mg/m² every 3 weeks and radiation at a dose of 66 Gy given in 33 fractions.
However compliance to this regimen often is insufficient due to high-dose-related toxicities.
Chemoradiotherapy with weekly cisplatin, dosed at 40 mg/m², is an alternative regimen associated with better compliance.
Kiyota and colleagues conducted a multi-institutional phase 2/phase 3 trial that included 261 patients aged 20 to 75 years with HNSCC.
Researchers randomly assigned patients to 3-weekly cisplatin in combination with radiotherapy (n = 132) or weekly cisplatin with radiotherapy (n = 129). All patients had postoperative high-risk features — microscopically positive margin and/or extranodal extension — and ECOG performance status of 0 to 1.
Median follow-up was 2.2 years.
Results showed a higher rate of 3-year OS among patients who received weekly cisplatin (71.6% vs. 59.1%; HR = 0.69; 99.1% CI, 0.37-1.3), with a one-sided P for noninferiority (.00272) that fell below the predetermined threshold (.00433).
Researchers reported 3-year RFS of 64.5% among patients assigned weekly cisplatin and 53% among those in the 3-weekly cisplatin group (HR = 0.71; 95% CI, 0.48-1.06).
The weekly regimen also appeared associated with lower rates grade 3 or higher neutropenia (35.3% vs. 48.8%), grade 2 or higher creatinine elevation (5.7% vs. 8.5%), and grade 2 or higher hearing impairment (2.5% vs. 7.8%). Rates of grade 2 or higher mucositis were comparable between the weekly and 3-weekly groups (59% vs. 55%).
For compliance, median total dose of cisplatin was 280 mg/m² (interquartile range [IQR], 250-299) for patients who received 3-weekly cisplatin in combination with radiotherapy and 239 mg/m² (IQR, 199-277) for patients who received weekly cisplatin with radiotherapy. Total radiation dose was 66 Gy in both groups.
The Data and Safety Monitoring Committee recommended halting the trial and publishing the results because the statistical boundary for OS noninferiority had met the prespecified stop criteria.
“Weekly [cisplatin] in combination with radiotherapy is a new standard treatment option for these patients,” Kiyota said. “A final analysis is planned after 5-year follow-up from final registration.”
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Kiyota N, et al. Abstract 6502. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.
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