A Phase 1b/2 Study of Alpelisib in Combination with Cetuximab in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma.
Target Oncol
; 18(6): 853-868, 2023 Nov.
Article
em En
| MEDLINE
| ID: mdl-37875771
ABSTRACT
BACKGROUND:
Alpelisib in combination with cetuximab showed synergistic anti-tumour activity in head and neck squamous cell carcinoma (HNSCC) models.OBJECTIVES:
The recommended phaseâ¯2 dose (RP2D) was determined in a phaseâ¯1b dose-escalation study. Phaseâ¯2 evaluated anti-tumour activity with a randomised part in cetuximab-naïve patients and a non-randomised part in cetuximab-resistant patients. PATIENTS ANDMETHODS:
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 300â¯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 HRâ¯1.12; 95%â¯CIâ¯0.69-1.82;â¯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 HRâ¯0.54;â¯95%â¯CIâ¯0.30-0.97;â¯P = 0.039). PFS per investigator assessment resulted in an unadjusted HR of 0.76 (95% CIâ¯0.49-1.19;â¯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-naïve 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias de Cabeça e Pescoço
/
Recidiva Local de Neoplasia
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article