The addition of weekly carboplatin following surgery and radiation therapy did not improve freedom from locoregional relapse (FFLRR) in patients with high-risk cutaneous head and neck squamous cell carcinoma (HNSCC).
In the TROG 05.01 trial, the 2-year rate of FFLRR was 88% (95% CI, 83-93) for patients who had radiation therapy (RT) alone compared with 89% (95% CI, 84-94) for those who received AUC 2 of once-weekly carboplatin in addition to radiation (CRT). The 5-year FFLRR rate was 83% (95% CI, 77-90) in the RT arm versus 87% (95% CI, 81-93) for the CRT arm (HR, 0.84; 95% CI, 0.46-1.55; P
Investigators found that the results from the sensitivity analysis with death as a competing event were almost identical between the 2 arms (HR, 0.85; 95% CI, 0.47-1.56; P
From April 2005 to July 2014, patients with HNSCC enrolled in the multicenter, open-label, randomized phase III trial at 22 sites in Australia and New Zealand. Among 310 evaluable patients, 157 were randomly assigned to RT and 153 were assigned to CRT. All patients underwent resection of the primary lesion, any type of parotidectomy, and/or any type of neck dissection. Superficial parotidectomy was the most common regional nodal surgery performed.
Initial RT in both arms consisted of conventionally fractionated daily treatment to a total of 60 Gy in 30 fractions over 6 weeks to the site of previous gross disease. However, investigators became concerned that 60 Gy may have been a suboptimal dose in the presence of microscopic positive margins, so a modification to include the option of 66 Gy in 33 fractions over 6.5 weeks was included in November 2008.
In the CRT arm, participants received weekly carboplatin beginning on day 1, 2, or 3 of the RT and repeated on the same day each week to a maximum of 6 doses.
The median age was 65 and 63 years for the RT and CRT arms, respectively. The vast majority of patients were men (94% in the RT arm and 92% in the CRT arm). Most patients in both groups had an ECOG performance status of 0.
In the RT arm, 78% of patients had high-risk nodal disease, 18% had advanced primary or in-transit disease, and 4% had high-risk nodal and advanced primary/in transit disease. In the CRT arm, 76% of patients had high-risk nodal disease, 20% had advanced primary or in-transit disease, and 5% had high-risk nodal and advanced primary/in transit disease.
Extracapsular nodal extension was present in 86 patients in the RT arm compared with 79 patients in the CRT arm.
The median RT dose was 60 Gy, and more than 90% of patients in both arms received the prescribed RT dose. In the CRT arm, 84% of patients received 6 doses of chemotherapy, with 11% requiring a dose reduction.
The 2-year disease-free survival (DFS) was 78% (95% CI, 72-85) and the 5-year DFS was 67% (95% CI, 60-76) in the RT arm compared with 83% (95% CI, 77-89) and 73% (95% CI, 66-81), respectively, in the CRT group (HR 0.85; 95% CI, 0.55-1.29; P
The 2-year overall survival (OS) was 88% in both groups. Five-year OS was 76% (95% CI, 69-84) in the RT arm and 79% (95% CI, 72-86) in the CRT arm (HR, 0.95; 95% CI, 0.58-1.57; P
There were no treatment-related deaths. The most common grade 1/2 adverse event (AE) in both groups was salivary gland (RT, 96%; CRT, 93%). Grade 3/4 AEs were uncommon except for dermatitis, which appeared in 49% of RT patients and 38% of CRT patients.
The most common any-grade chemotherapy-related AE was grade 1/2 nausea, observed in 55% of CRT patients.
Porceddu SV, Bresel M, Poulsen MG, et al. Postoperative concurrent chemoradiotherapy versus postoperative radiotherapy in high-risk cutaneous squamous cell carcinoma of the head and neck: the randomized phase III TROG 05.01 trial [published online March 14, 2018]. J Clin Oncol. doi: 10.1200/JCO.2017.77.0941.