Induction Chemotherapy Followed by Cetuximab Radiotherapy Is Not Superior to Concurrent Chemoradiotherapy for Head and Neck Carcinomas: Results of the GORTEC 2007-02 Phase III Randomized Trial

Abstract

Purpose Both concurrent chemoradiotherapy (CT-RT) and cetuximab radiotherapy (cetux-RT) have been established as the standard of care for the treatment of locally advanced squamous cell carcinoma of the head and neck. It was not known whether the addition of induction chemotherapy before cetux-RT could improve outcomes compared with standard of care CT-RT. Patients and Methods The current trial was restricted to patients with nonmetastatic N2b, N2c, or N3 squamous cell carcinoma of the head and neck and fit for taxotere, cisplatin, fluorouracil (TPF). Patients were randomly assigned to receive three cycles of TPF followed by cetux-RT versus concurrent carboplatin fluorouracil and RT as recommended in National Comprehensive Cancer Network guidelines. The trial was powered to detect a hazard ratio (HR) of 0.66 in favor of TPF plus cetux-RT for progression-free survival at 2 years. The inclusion of 180 patients per arm was needed to achieve 80% power at a two-sided significance level of .05. Results Between 2009 and 2013, 370 patients were included. All patients and tumors characteristics were well balanced between arms. There were more cases of grade 3 and 4 neutropenia in the induction arm, and the induction TPF was associated with 6.6% treatment-related deaths. With a median follow-up of 2.8 years, 2-year progression-free survival was not different between both arms (CT-RT, 0.38 v TPF + cetux-RT, 0.36; HR, 0.93 [95% CI, 0.73 to 1.20]; P = .58). HR was 0.98 (95% CI, 0.74 to 1.3; P = .90) for locoregional control and 1.12 (95% CI, 0.86 to 1.46; P = .39) for overall survival. These effects were observed regardless of p16 status. The rate of distant metastases was lower in the TPF arm (HR, 0.54 [95% CI, 0.30 to 0.99]; P = .05). Conclusion Induction TPF followed by cetux-RT did not improve outcomes compared with CT-RT in a population of patients with advanced cervical lymphadenopathy.

The neoadjuvant paradigm reinvigorated: a review of pre-surgical immunotherapy in HNSCC

“…More recently, GORTEC 2007-02 showed no improvement in PFS or OS with induction chemotherapy followed by cetuximab radiotherapy compared to chemoradiotherapy, though there was a reduction in the rate of distant metastases (DM) in the induction chemotherapy arm [8]. p16 status was stratified (n = 26, 31% in CRT arm, n = 19, 21% in TPF and cetuximab RT arm), but results were consistent with the overall population.…”

Induction chemotherapy followed by radiotherapy for N3 head and neck squamous cell carcinoma

“…It is conceivable that the benefit of ICT could be expected in N3 HNSCC patients who are at increased risk of distant metastases. 8,12 This study represents a retrospective single-institution analysis of the therapeutic results in 120 HNSCC patients with N3 disease treated with induction chemotherapy followed by definitive chemoradiation/radiotherapy. To our knowledge, this study is the largest series focusing on the role of induction chemotherapy in N3 HNSCC in a single center.…”

“…4 Adding taxane to cisplatin and 5-fluorouracil (PF) has been shown to improve response rate, time to progression (TTP), and overall survival (OS) compared with PF. 8,9 Thus, the applicability of the outcomes of these trials to patients with N3 HNSCC is unclear. Unfortunately, only 22% and 11% of patients with N3 disease had been enrolled in the two studies despite this being a stated goal of study accrual.…”

“…Unfortunately, only 22% and 11% of patients with N3 disease had been enrolled in the two studies despite this being a stated goal of study accrual. 8,9 Thus, the applicability of the outcomes of these trials to patients with N3 HNSCC is unclear.…”

Plattenepithelkarzinome der Kopf-Hals-Region (SCCHN)

“…Bei Inoperabilität steht die de finitive RCT zu Verfügung. Versuche, die weiterhin schlechte Pro gnose der Patienten mit N2 und N3Status durch eine Induktion schemotherapie zu verbessern, konnten bisher keinen Vorteil für das progressionsfreie Überleben oder das Gesamtüberleben de monstrieren und führen zudem zu einer erhöhten Toxizität[11].…”