Induction chemotherapy (IC) followed by radiotherapy (RT) versus 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 carried out 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/m 2 /day 1, 5-FU (F) 750 mg/m 2 /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.

Organ Preservation for Advanced Laryngeal Cancer: Experience with Concurrent Chemoradiation Therapy

“…The purpose of the study was to test the hypothesis that the addition of cetuximab to induction chemotherapy (IC) and radiotherapy improves LFS. Response to first IC cycle (IC-1) with >30% endoscopically estimated tumor surface shrinkage was used to define early responders; early salvage TL was recommended to non-responders [24]. This empirical endoscopically assessed cut-off of >30% was introduced the first time in literature.…”

The failure of cetuximab-based de-intensified regimes for HPV-positive OPSCC: A radiobiologists perspective

“…One question that comes into mind is whether this lack of effectiveness is specific for the HPV-positive fraction of OPSCC/HNSCC tumors, which clearly have a different biology than HPV-negative. Focusing on prospective trials with mostly HPV-negative tumors, cetuximab failed to enhance survival when added to chemoradiation in RTOG-0522 and when added to induction chemotherapy and subsequent RT in DeLOS-II [16] , [17] . Furthermore, the alternative anti-EGFR antibodies panitumumab (CONCERT-1&2) and zalutumumab (DAHANCA 19) also failed to compete with cisplatin when added to RT or to enhance survival when added to chemoradiation, as well as the EGFR-inhibitor erlotinib [18] , [19] , [20] , [21] .…”

Perspectives of Induction With Chemo and/or Immune Check Point Inhibition in Head and Neck Organ Preservation Treatment

“…Currently, in organ preservation for laryngeal and hypopharyngeal cancers ICT is the most reasonable alternative to concurrent CRT. Attention has been directed toward the identification of patients with an excellent response to ICT who are possible candidates for organ preservation (6, 7). Until now, there is no prospectively approved reliable method for the prediction of response of HNSCC patients to chemotherapy.…”