Chemoradiotherapy plus cisplatin administered weekly was found to be non-inferior to cisplatin once every 3 weeks for patients with high-risk locally advanced squamous cell carcinoma of the head and neck.
Outcomes in patients with high-risk locally advanced squamous cell carcinoma of the head and neck demonstrated noninferiority of chemoradiotherapy plus weekly cisplatin compared with cisplatin every 3 weeks, according to a study published in The Journal of Clinical Oncology.
The median follow-up was 2.2 years. The overall survival (OS) for patients receiving weekly chemoradiotherapy and cisplatin was non-inferior to the cisplatin every 3 weeks regimen (Hazard ratio [HR], 0.69; 99.1% CI, 0.37-1.27; one-sided P for noninferiority = .0027 < .0043). At the time of the interim analysis, 44 patients in the cisplatin alone arm compared with 32 in the weekly arm. The estimated 2-year OS rate was 74.2% and the 3-year rate was 59.1% in the cisplatin alone arm vs 77.7% and 71.6%, respectively in the weekly arm.
A total of 261 patients enrolled on the trial and included in the intent-to-treat analyses, 132 of whom were in the cisplatin alone arm and 129 were in the chemoradiotherapy arm. In the per-protocol analysis, 251 patients were included.
In the cisplatin alone arm, patients received cisplatin at 100 mg/m2 once every 3 weeks for 3 cycles during the radiation therapy period, or once within 14 days from the day of completion of radiation. In the weekly arm, patients received 40 mg/m2 of cisplatin once a week for 7 cycles during the radiation therapy period.
A total of 88 patients experienced disease recurrence, including 51 in the cisplatin alone armand 37 in the weekly arm. The relapse-free survival (RFS) HR was 0.71 (95% CI, 0.48-1.06) and for local RFS, the HR was 0.73 (95% CI, 0.47-1.13).
With a median follow-up of 3.5 years, the HR for death was 0.75 (95% CI, 0.50-1.13). In terms of causes of death, 2 deaths were treatment related in the weekly arm. In the weekly arm, investigators reported a lower number of deaths and fewer cancer-specific deaths.
Adverse effects (AEs) of special interest were prespecified in the protocol since they were expected to be more frequent in the cisplatin alone armvs the weekly arm, and included neutropenia, infection, hearing impairment, and renal impairment. Data on acute hematologic AEs of special interest of grade 3 or higher showed that neutropenia was less frequent in the weekly arm at 35% vs 49% in the cisplatin alone arm. Additionally, thrombocytopenia was less frequent in the cisplatin alone armat 66% vs 84% in the weekly arm.
Non-hematologic AEs of special interest included renal impact (40% vs 30%), hearing impairment (17% vs 7%), and tinnitus (25% vs 5%) in the cisplatin alone armand weekly groups, respectively.
In total, 79.8% of patients in the cisplatin alone vs 81.1% in the weekly groups had at least 1grade 3 AE was (P = .87), and the rates of grade 4 AEs were 18.6% vs 8.2% (P = .017), respectively. Discontinuation in the 3-weekly arm occurred because of treatment-related AE such as xerostomia (n = 1), mucositis (n = 1), and persistent nausea (n = 1). In the weekly arm, discontinuation occurred with 2 patients from protocol treatment, including 1 each from anorexia and febrile neutropenia. There were 2 treatment-related deaths in the weekly arm from febrile neutropenia and laryngeal edema.
Kiyota N, Tahara M, Mizusawa J, et al. Weekly cisplatin plus radiation for postoperative head and neck cancer (JCOG1008): a multicenter, noninferiority, phase II/III randomized controlled trial. J Clin Oncol. Published online March 1, 2022. doi:10.1200/JCO.21.01293