Immuno-chemotherapy as single treatment modality for larynx preservation (ICoLP): Co-primary endpoints and safety results.
Authors: Ferrarotto Renata , Johnson Faye M. , Hutcheson Kate A. , Sui Dawen , Johnson Jason M. , Ebersole Barbara , Mott Frank , Lewis Carol M. , Bonini Flavia , Hoff Camilla Oliveira , Mitani Yoshitsugu , Cortez Maria Angelica , Bell Diana , El-Naggar Adel K. , Gunn Gary Brandon , Fuller Clifton Dave , Myers Jeffrey , Lee J. Jack , Rosenthal David Ira , Diaz Eduardo 
Published: June 2023

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Background: Optimal treatment of larynx squamous cell carcinoma (LC) maximizes functional outcomes and survival. Surgery and radiotherapy (RT) may lead to significant morbidity, notably dysphonia and dysphagia. Our group published durable pathologic complete response (pCR) with normal function in 33% of patients (pts) with stage II-IV LC treated with single modality chemotherapy. We hypothesized that pembrolizumab (P), cisplatin (C), and docetaxel (D) will cure a subset of LC pts and preserve larynx function. Methods: Eligible pts had stage II-III LC measurable per RECIST 1.1. Treatment consisted of P 200 mg, C 75 mg/m2 or carboplatin AUC 6, and D 75 mg/m2 IV Q3W. After 2 PCD cycles, pts with radiological response (complete [CR], partial [PR], or stable disease [SD]) received 2 additional PCD cycles. After 4 cycles, pts underwent larynx biopsy. Those with pCR received 4 doses of consolidation P; those without pCR received local therapy (LT; RT or surgery). Co-primary endpoints are disease control rate (DCR; CR+PR+SD) after 2 PCD cycles and pCR rate after 4 cycles. Secondary endpoints include safety, laryngeal preservation rate, relapse-free survival, and swallow function. Per Bayesian design (H0: 65% DCR, 15% pCR; H1: 85% DCR, 30% pCR), we reject H0 if of 25 pts, 19 have DCR or > 7 achieve pCR (10% alpha, 88% power). Results: 24 pts enrolled from 8/9/19-12/15/22, 62.5% were stage III (54.2% were T3 and 16.7% were N1); 23 were evaluable for the efficacy endpoints. DCR was 100% with 74% (17/23) being objective responses and 52% CR; pCR rate to date is 77.3% (17/22; 1 pt is on-treatment). 6 of 17 (35%) pts with pCR developed recurrence, mostly (4/6) within 4 months of pCR, and were salvaged with LT. 5 pCR lasted ≥ 1 y; 2 additional pCR pts unable to perform serial laryngoscopy or imaging due to loss of insurance (n = 1) or moving to another state (n = 1) have not had clinical recurrence for ≥ 2 ys. The median follow-up is 17.2 mos (range: 1.4 – 39.4 mos). One patient who refused LT at early recurrence was lost to follow-up and eventually underwent a total laryngectomy and RT then recurred locally and died of disease. An additional patient who had pCR with early recurrence received definitive RT with CR, but subsequently developed a solitary lung metastasis treated with RT; 2 pts remain on trial treatment. The most common treatment-related adverse events (TRAE) were fatigue (91.6%), anemia (79%), diarrhea (45.8%), and nausea (41.6%). 10 grade 3-4 TRAE were reported in 5 (20.8%) pts with the most common being neutropenia (3/24, 12.5%) and anemia (2/24; 8.3%). 2 pts discontinued PCD treatment due to toxicity. Conclusions: The study reached its primary endpoint with a DCR of 100% (23/23) and a pCR in 77.3% (17/22) of evaluable patients; 5 pCR last ≥ 1 y. Recurrences after pCR occurred stressing the importance of close follow-up. Updated efficacy and swallow function results will be presented at the meeting. Clinical trial information: NCT04030455 .