Τίτλος:
Cobimetinib plus atezolizumab in BRAFV600 wild-type melanoma: primary results from the randomized phase III IMspire170 study
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Background: Emerging data suggest that the combination of MEK inhibitors and immunotherapeutic agents may result in improved efficacy in melanoma. We evaluated whether combining MEK inhibition and immune checkpoint inhibition was more efficacious than immune checkpoint inhibition alone in patients with previously untreated BRAFV600 wild-type advanced melanoma. Patients and methods: IMspire170 was an international, randomized, open-label, phase III study. Patients were randomized 1 : 1 to receive cobimetinib (60 mg, days 1-21) plus anti-programmed death-ligand 1 atezolizumab (840 mg every 2 weeks) in 28-day cycles or anti-programmed death-1 pembrolizumab (200 mg every 3 weeks) alone until loss of clinical benefit, unacceptable toxicity, or consent withdrawal. The primary outcome was progression-free survival (PFS), assessed by an independent review committee in the intention-to-treat population. Results: Between 11 December 2017, and 29 January 2019, 446 patients were randomized to receive cobimetinib plus atezolizumab (n = 222) or pembrolizumab (n = 224). Median follow-up was 7.1 months [interquartile range (IQR) 4.8-9.9] for cobimetinib plus atezolizumab and 7.2 months (IQR 4.9-10.1) for pembrolizumab. Median PFS was 5.5 months [95% confidence interval (CI) 3.8-7.2] with cobimetinib plus atezolizumab versus 5.7 months (95% CI 3.7-9.6) with pembrolizumab [stratified hazard ratio 1.15 (95% CI 0.88-1.50); P = 0.30]. Hazard ratios for PFS were consistent across prespecified subgroups. In exploratory biomarker analyses, higher tumor mutational burden was associated with improved clinical outcomes in both treatment arms. The most common grade 3-5 adverse events (AEs) were increased blood creatine phosphokinase (10.0% with cobimetinib plus atezolizumab versus 0.9% with pembrolizumab), diarrhea (7.7% versus 1.9%), rash (6.8% versus 0.9%), hypertension (6.4% versus 3.7%), and dermatitis acneiform (5.0% versus 0). Serious AEs occurred in 44.1% of patients with cobimetinib plus atezolizumab and 20.8% with pembrolizumab. Conclusion: Cobimetinib plus atezolizumab did not improve PFS compared with pembrolizumab monotherapy in patients with BRAFV600 wild-type advanced melanoma. © 2020 European Society for Medical Oncology
Συγγραφείς:
Gogas, H.
Dréno, B.
Larkin, J.
Demidov, L.
Stroyakovskiy, D.
Eroglu, Z.
Francesco Ferrucci, P.
Pigozzo, J.
Rutkowski, P.
Mackiewicz, J.
Rooney, I.
Voulgari, A.
Troutman, S.
Pitcher, B.
Guo, Y.
Yan, Y.
Castro, M.
Mulla, S.
Flaherty, K.
Arance, A.
Περιοδικό:
Annals of Oncology
Εκδότης:
Elsevier Ireland Ltd
Λέξεις-κλειδιά:
atezolizumab; cobimetinib; creatine kinase; pembrolizumab; programmed death 1 ligand 1; antineoplastic agent; atezolizumab; azetidine derivative; B Raf kinase; BRAF protein, human; cobimetinib; monoclonal antibody; piperidine derivative, abdominal pain; acne; adult; aged; anemia; arthralgia; Article; asthenia; BRAFV600 wild type melanoma; BRAFV600 wild type melanoma; cancer combination chemotherapy; cancer staging; clinical outcome; constipation; controlled study; creatine kinase blood level; decreased appetite; diarrhea; drug efficacy; drug response; drug safety; fatigue; female; fever; follow up; headache; human; hypertension; hypertransaminasemia; hypophosphatemia; intention to treat analysis; lung embolism; maculopapular rash; major clinical study; male; melanoma; monotherapy; multiple cycle treatment; nausea; oncological parameters; open study; peripheral edema; phase 3 clinical trial; priority journal; progression free survival; protein expression; pruritus; randomized controlled trial; rash; sepsis; treatment duration; tumor mutational burden; vomiting; clinical trial; genetics, Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Azetidines; Humans; Melanoma; Piperidines; Proto-Oncogene Proteins B-raf
DOI:
10.1016/j.annonc.2020.12.004
