Biomarkers of treatment benefit with atezolizumab plus vemurafenib plus cobimetinib in BRAFV600 mutation-positive melanoma.
Ann Oncol
; 33(5): 544-555, 2022 05.
Article
en En
| MEDLINE
| ID: mdl-35131452
ABSTRACT
BACKGROUND:
The phase III IMspire150 study (NCT02908672) demonstrated significantly improved progression-free survival (PFS) with atezolizumab, vemurafenib, and cobimetinib (atezolizumab group) versus placebo, vemurafenib, and cobimetinib (control group) in patients with BRAFV600-mutated advanced melanoma. We report exploratory biomarker analyses to optimize targeting of patients who are more likely to benefit from triplet combination therapy. PATIENTS ANDMETHODS:
Five hundred fourteen patients were randomized to atezolizumab (n = 256) or control (n = 258). Outcomes were evaluated in subgroups defined by key biomarkers, including programmed death-ligand 1 (PD-L1) expression, lactate dehydrogenase (LDH) level, tumor mutational burden (TMB), and interferon-γ (IFN-γ) gene signature. Exploratory recursive partitioning analysis was then used to model associations between PFS and baseline covariates, including key biomarkers.RESULTS:
PFS benefit for atezolizumab versus control was greater in patients with high TMB [≥10 mutations/Mb; hazard ratio (HR) 0.73; 95% confidence interval (CI) 0.52-1.02; P = 0.067] versus low TMB (<10 mutations/Mb; HR 0.92; 95% CI 0.65-1.30; P = 0.64) and similar between patients with strong IFN-γ (≥median; HR 0.76; 95% CI 0.54-1.06) versus weak IFN-γ (CONCLUSIONS:
Treatment benefits in the atezolizumab group seemed to be most evident in patients with elevated LDH and PD-L1- tumors. LDH remains the primary predictor of outcomes regardless of treatment. IFN-γ and TMB further differentiate outcomes for patients treated with atezolizumab, vemurafenib, and cobimetinib.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Proteínas Proto-Oncogénicas B-raf
/
Melanoma
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Ann Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2022
Tipo del documento:
Article