Induction chemotherapy (IC) followed by radiotherapy (RT) vs. cetuximab plus IC and RT in advanced laryngeal/hypopharyngeal cancer resectable only by total laryngectomy – final results of the larynx organ preservation trial DeLOS-II

Abstract

Background

The German multicenter randomized phase-II larynx-organ preservation (LOP) trial DeLOS-II was performed to prove the hypothesis that cetuximab (E) added to induction chemotherapy (IC) and radiotherapy improves laryngectomy-free survival (LFS; survival with preserved larynx) in locally advanced laryngeal/hypopharyngeal cancer (LHSCC).

Patients and methods

Treatment-naïve patients with stage III/IV LHSCC amenable to total laryngectomy (TL) were randomized to three cycles IC with TPF (docetaxel [T] and cisplatin [P] 75 mg/m²/day 1, 5-FU [F] 750 mg/m²/day days 1-5) followed by radiotherapy (69.6 Gy) without (A) or with (B) standard dose cetuximab for 16 weeks throughout IC and radiotherapy (TPFE). Response to first IC-cycle (IC-1) with ≥30% endoscopically estimated tumor surface shrinkage (ETSS) was used to define early responders; early salvage TL was recommended to non-responders. The primary objective was 24-months LFS above 35% in arm B.

Results

Of 180 patients randomized (7/2007-9/2012), 173 fulfilled eligibility criteria (A/B: larynx 44/42, hypopharynx 41/46). Because of 4 therapy-related deaths among the first 64 randomized patients, 5-FU was omitted from IC in the subsequent 112 patients reducing further fatal toxicities. Thus, IC was TPF in 61 patients and TP in 112 patients, respectively. The primary objective (24-months LFS above 35%) was equally met by arms A (40/85, 47.1%) as well as B (41/88, 46.6%). 123 early responders completed IC+RT; their overall response rates (TPF/TP) were 94.7%/87.2% in A vs. 80%/86.0% in B. The 24-months overall survival (OS) rates were 68.2% and 69.3%.

Conclusions

Despite being accompanied by an elevated frequency in adverse events, the IC with TPF/TP plus cetuximab was feasible but showed no superiority to IC with TPF/TP regarding LFS and OS at 24 months. Both early response and 24-months LFS compare very well to previous LOP trials and recommend effective treatment selection and stratification by ETSS.

Clinical trial information

NCT00508664