Final results of the randomized phase II DeLOS-II trial: Induction chemotherapy (IC) followed by radiotherapy (R) vs. cetuximab (E) plus IC and R for functional larynx preservation in resectable laryngeal and hypopharyngeal cancer (LHSCC).

Abstract

6025 Background: To evaluate the impact of E added throughout IC and R on the rate of two-year functional laryngectomy free survival (fLFS). Methods: Untreated patients (pts) with stage III/IV LHSCC, amenable to resection by total laryngectomy, were randomized to three cycles of IC with TPF (docetaxel and cisplatin 75 mg/m² day 1 and F 750 mg/m²/day on days 1-5) followed by R (69,6Gy) without (arm A) or with (arm B) standard dose of cetuximab for 16 weeks throughout IC and R. In case of non-response after the first IC cycle, salvage laryngectomy was performed. The primary objective was a 2-year fLFS rate above 35% (lower bound of 80%-CI) in the experimental arm. Results: Of180 pts randomized (7.2007-9.2012), 173 fulfilled ITT criteria. Due to 4 therapy related deaths among the first 64 randomized pts, F was omitted from IC in 2.2009 with no further treatment related deaths in the remaining 112 pts. Table 1 summarizes rates of response, laryngectomy, fLFS and OS. The primary objective of an fLFS above 35% was met, however, the control arm also met objectives. 31.8% (arm A) and 22.7% (arm B) of patients did not respond to first cycle IC. Conclusions: IC with TPFE/TPE was feasible and showed a trend towards being more effective compared to TPF/TP in terms of rates of fLFS and OS. The early response rate to IC of 77.3% and the 1 and 2 year fLFS rates of 63.6% and 46.6%, respectively compare very well to previous larynx preservation trials and suggest effective treatment selection and stratification by early response evaluation to IC. Clinical trial information: NCT00508664.Efficacy and outcome data. Arm A TP(F) – > R Arm B TP(F) – > R plus cetuximab OR (95%CI) Localisation: : : Larynx 44 42 Hypopharynx 41 46 TPF 30 31 TP 55 57 ORR* (n = 126) : : TPF 94.7% 80.0% TP 79.1% 94.9% Laryngectomy 25.9% 33.0% fLFS at 6 months 65.9% 77.3% 0.5680 (0.2905-1.1105) fLFS at 1 year 55.3% 63.6% 0.7068 (0.3842-1.3001) fLFS at 2 years 44.7% 46.6% 0.9268 (0.5094-1.6863) OS at 2 years 68.2% 69.3% 0.9508 (0.4997-1.8091) OR: Odds Ratio; *at final examination