A Phase 1b/2 Study of Alpelisib in Combination with Cetuximab in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Razak, ARA; Wang, HM; Chang, JY; Ahn, MJ; Munster, P; Blumenschein, G, Jr; Solomon, B; Lim, DWT; Hong, RL; Pfister, D; Saba, NF; Lee, SH; van Herpen, C; Quadt, C; Bootle, D; Blumenstein, L; Demanse, D; Delord, JP

Author(s): Razak, ARA; Wang, HM; Chang, JY; Ahn, MJ; Munster, P; Blumenschein, G, Jr; Solomon, B; Lim, DWT; Hong, RL; Pfister, D; Saba, NF; Lee, SH; van Herpen, C; Quadt, C; Bootle, D; Blumenstein, L; Demanse, D; Delord, JP;
Details: Publication Year 2023,Volume 18,Issue #6,Page 853-868
Journal Title: Targeted Oncology
Publication Type: Research article
Abstract: BACKGROUND: Alpelisib in combination with cetuximab showed synergistic anti-tumour activity in head and neck squamous cell carcinoma (HNSCC) models. OBJECTIVES: The recommended phase 2 dose (RP2D) was determined in a phase 1b dose-escalation study. Phase 2 evaluated anti-tumour activity with a randomised part in cetuximab-naive patients and a non-randomised part in cetuximab-resistant patients. PATIENTS AND METHODS: Alpelisib was administered in 28 d cycles as whole tablets, suspension from crushed tablets or suspension from dispersible tablets in patients with platinum-resistant, recurrent/metastatic HNSCC. RESULTS: The RP2D determined for alpelisib was 300 mg/d. Alpelisib-cetuximab achieved an overall response rate of 25% and 9.9% and disease control rate of 75% and 43.7% in phase 1b and phase 2 studies, respectively. Median progression-free survival (PFS) per central review was 86 d for combination treatment and 87 d for cetuximab monotherapy (unadjusted HR 1.12; 95% CI 0.69-1.82; P > 0.05). When adjusted for baseline covariates [sum of longest diameters from central data, haemoglobin and white blood cell (WBC), the results favoured combination treatment (adjusted HR 0.54; 95% CI 0.30-0.97; P = 0.039). PFS per investigator assessment resulted in an unadjusted HR of 0.76 (95% CI 0.49-1.19; P > 0.05) favouring combination treatment. The median PFS in cetuximab-resistant patients was 3.9 months. CONCLUSIONS: The addition of alpelisib to cetuximab did not demonstrate a PFS benefit in cetuximab-naive patients with advanced HNSCC. The alpelisib-cetuximab combination showed moderate activity in cetuximab-resistant patients, with a consistent safety profile. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01602315; EudraCT 2011-006017-34.
Publisher: Springer Nature
Department(s): Medical Oncology
PubMed ID: 37875771
Publisher's Version: https://doi.org/10.1007/s11523-023-00997-z
Open Access at Publisher's Site: https://doi.org/10.1007/s11523-023-00997-z
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-12-05 12:35:42

Last Modified: 2023-12-05 12:50:03