Weekly carboplatin did not confer any additional benefit when paired with postoperative radiotherapy for high-risk cutaneous squamous cell carcinoma of the head and neck, according to findings from a randomized phase 3 study conducted in Australia and New Zealand.
“Concurrent, platinum-based, postoperative chemoradiotherapy has demonstrated improvement in locoregional control, PFS and OS compared with radiotherapy alone [among] patients with high-risk mucosal squamous cell carcinoma of the head and neck,” Sandro Virgilio Porceddu, MD, radiation oncologist at Princess Alexandra Hospital in Australia, and colleagues wrote. “Although many have extrapolated the use of postoperative chemoradiotherapy from these studies to cutaneous squamous cell carcinoma of the head and neck, there is no high-level evidence to support its use in this setting.”
The effect of 60 Gy or 66 Gy of radiotherapy with or without weekly carboplatin on freedom from locoregional relapse following surgery served as the primary objective. Secondary outcomes included DFS and OS.
Researchers randomly assigned 321 patients, 310 of whom received treatment with radiotherapy alone (n = 157) or chemoradiotherapy (n = 153). Seventy-seven percent (n = 238) of patients had high-risk nodal disease, 19% (n = 59) had high-risk primary or in-transit disease, and 4% (n = 13) had both.
The median dose for radiotherapy was 60 Gy. Most patients (84%) assigned to chemoradiotherapy underwent six cycles of carboplatin.
Median follow-up was 60 months.
Two-year freedom from locoregional relapse rates were 88% (95% CI, 83-93) in the radiotherapy group and 89% (95% CI, 84-94) in the chemoradiotherapy group. At 5 years, rates were 83% (95% CI, 77-90) in the radiotherapy group and 87% (95% CI, 81-93) for the chemoradiotherapy group. The difference did not show a significant benefit with chemoradiotherapy (HR = 0.84; 95% CI, 0.46-1.55).
The two groups also showed no significant differences in DFS or OS.
Locoregional failure was the most common site of first treatment failure. In both arms, 7% of patients experienced isolated distant metastases as the first site of failure.
Patients in both arms tolerated treatment equally well, and carboplatin did not appear to cause any toxicity. Few grade 3 or grade 4 late toxicities occurred in either arm.
Aarti K. Bhatia
After 2011, accrual for the study slowed because of the increasing use of intensity-modulated radiation as standard treatment, whereas the study did not allow for this therapy, Aarti K. Bhatia, MD, MPH, assistant professor of medicine at Yale Cancer Center, and colleagues wrote in a related editorial. Recruitment ended after the researchers had randomly assigned 321 patients.
“Aspects of the clinical design including the statistical assumptions, the failure to complete accrual, patient selection and the regimen under study all contributed to reducing the power of this study to detect a meaningful benefit from the addition of chemotherapy to postoperative radiotherapy in cutaneous squamous cell carcinoma, if one exists,” Bhatia and colleagues wrote. “Closer examination of these aspects of this report may help establish the direction for future trials in this setting.” – by Andy Polhamus
Disclosures: Porceddu reports consultant/advisory roles with Merck Serono, Merck Sharpe & Dohme, Oral Oncology and UpToDate, as well as travel, accommodations and expenses from Merck Serono and Merck Sharpe & Dohme. Please see the full study for all other authors’ relevant financial disclosures. Bhatia reports a consultant/advisory role with Bristol-Myers Squibb and research funding from Boehringer Ingelheim. Please see the full editorial for all other authors’ relevant financial disclosures.