The European Larynx Organ Preservation Study [MK-3475-C44]

Abstract

The European Larynx Organ Preservation Study (ELOS; NCT06137378) is a prospective, randomized, open-label, two-armed parallel group controlled, phase II multicenter larynx organ preservation (LOP) trial in locoregionally advanced (LA) stage III, IVA/B head and neck squamous cell carcinoma of the larynx or hypopharynx (LHSCC) amenable for total laryngectomy (TL) with PD-L1 expression within tumor tissue biopsy, calculated as CPS ≥ 1. Induction chemotherapy (IC) with docetaxel and cisplatin (TP) followed by radiation will be compared to TP plus PD-1 inhibition by pembrolizumab (MK-3475; 200 mg i.v. starting day 1 q3w for 17 cycles). After a short induction early response evaluation (ERE) 21 ± 3 days after the first cycle of IC (IC-1), responders achieving endoscopic estimated tumor surface shrinkage (ETSS) ≥30% will get an additional two cycles of IC followed by intensity-modulated radiotherapy 70-72 Gy (EQD2/α/β = 10) aiming at LOP. Nonresponders (ETSS < 30% or progressing disease) will receive TL and bilateral neck dissection followed by postoperative radiation or chemoradiation as recommended by the clinic's multidisciplinary tumor board. Pembrolizumab treatment will be continued in the intervention arm regardless of ETSS status after IC-1 in both responders and laryngectomized nonresponders, independent of subsequent decisions on adjuvant therapy after TL.

Clinical trial registration: clinicaltrials.gov, identifier NCT06137378.

Keywords: head and neck squamous cell carcinoma (HNSCC); immune checkpoint blockade PD-1:PD-L1 axis; inductionchemotherapy (IC); larynx and hypopharynx cancer (LHSCC); larynx organ function; larynx organ preservation (LOP); randomized controlled trial (RCT); total laryngectomy (TL).

Figure 1

Study design of European Larynx Organ Preservation Study (ELOS) [MK-3475-C44] (NCT06137378), a randomized controlled trial comparing the outcome of patients in arm A (control) treatment according to the medication and radiation protocol as in the DeLOS-II LOP trial (2) with the same treatment plus additional pembrolizumab (over 12 months) in the experimental arm (B; light green). CPS: combined positive score; R, randomization; TP, induction chemotherapy utilizing T, docetaxel, P, cisplatin (75 mg/m² each per cycle); Early response evaluation (ERE) according to DeLOS-II criteria: PR, partial response ≥ 30% endoscopic tumor surface shrinkage (ETSS) after one cycle; PD/SD, progressing disease or insufficient response < 30% ETSS; TL, total laryngectomy; ND, neck dissection; RT, radiotherapy; CRT, concomitant cisplatin-based chemo-radiotherapy.