Publications by authors named "Valeriy Breder"
Introduction: Atezolizumab plus bevacizumab significantly improved overall survival (OS) and progression-free survival (PFS) versus sorafenib in patients with unresectable hepatocellular carcinoma (HCC) in IMbrave150. Efficacy and safety in patient subpopulations with Vp4 portal vein tumor thrombosis (PVTT) and other high-risk prognostic factors are reported.
Methods: IMbrave150 was a global, randomized (2:1), open-label, phase 3 study in systemic treatment-naive patients with unresectable HCC; OS and PFS were co-primary endpoints.
Background: In the preplanned interim analysis of the TOPAZ-1 study, durvalumab plus gemcitabine-cisplatin significantly improved overall survival versus placebo plus gemcitabine-cisplatin in participants with advanced biliary tract cancer. We aimed to report updated overall survival and safety data from TOPAZ-1 with additional follow-up and data maturity beyond the interim analysis.
Methods: TOPAZ-1 was a phase 3, randomised, double-masked, placebo-controlled, global study done at 105 sites in 17 countries.
Article Synopsis
- - This study evaluated the safety and effectiveness of Debio 1347, a new oral drug targeting FGFR fusions in patients with advanced solid tumors, focusing on its ability to produce objective responses and other outcomes in different cancer types.
- - A total of 63 patients participated, with only a 5% objective response rate, leading to the trial's early termination due to lower-than-expected effectiveness, despite manageable side effects like hyperphosphatemia and stomatitis.
- - The findings suggest that while the drug has some tolerance, its lack of significant efficacy means it should not undergo further testing for FGFR fusion tumors; the study also provided insight into the characteristics of FGFR fusions in solid tumors.
Article Synopsis
- The TOPAZ-1 study investigated the effectiveness of durvalumab, a PD-L1 inhibitor, in combination with gemcitabine and cisplatin for treating advanced biliary tract cancer, showing significant survival benefits over the placebo.
- Participants aged 18 or older were randomly assigned to receive either the treatment or placebo, with their quality of life measured using specific questionnaires during the study.
- Findings from patient-reported outcomes are discussed, highlighting how the treatments impacted their quality of life based on decline metrics.
Background: Systemic therapies have improved the management of hepatocellular carcinoma, but there is still a need to further enhance overall survival in first-line advanced stages. This study aimed to evaluate the addition of pembrolizumab to lenvatinib versus lenvatinib plus placebo in the first-line setting for unresectable hepatocellular carcinoma.
Methods: In this global, randomised, double-blind, phase 3 study (LEAP-002), patients aged 18 years or older with unresectable hepatocellular carcinoma, Child Pugh class A liver disease, an Eastern Cooperative Oncology Group performance status of 0 or 1, and no previous systemic treatment were enrolled at 172 global sites.
Introduction: KEYNOTE-240 showed a favorable benefit/risk profile for pembrolizumab versus placebo in patients with sorafenib-treated advanced hepatocellular carcinoma (HCC); however, prespecified statistical significance criteria for overall survival (OS) and progression-free survival (PFS) superiority were not met at the final analysis. Outcomes based on an additional 18 months of follow-up are reported.
Methods: Adults with sorafenib-treated advanced HCC were randomized 2:1 to pembrolizumab 200 mg intravenously every 3 weeks or placebo.
Article Synopsis
- The HIMALAYA study compared the effectiveness of the STRIDE regimen (tremelimumab plus durvalumab) and durvalumab alone against sorafenib for treating unresectable hepatocellular carcinoma (HCC), a difficult-to-treat liver cancer.
- Results showed that participants receiving STRIDE lived longer and had a lower risk of worsening quality of life compared to those taking sorafenib, while those on durvalumab alone had similar survival to the sorafenib group.
- The findings indicate that STRIDE is a more effective treatment option than sorafenib for patients with unresectable HCC, with manageable side effects associated with the immunotherapy drugs.
BACKGROUND: A single, high priming dose of tremelimumab (anti-cytotoxic T lymphocyte–associated antigen 4) plus durvalumab (anti–programmed cell death ligand-1), an infusion regimen termed STRIDE (Single Tremelimumab Regular Interval Durvalumab), showed encouraging clinical activity and safety in a phase 2 trial of unresectable hepatocellular carcinoma. METHODS: In this global, open-label, phase 3 trial, the majority of the patients we enrolled with unresectable hepatocellular carcinoma and no previous systemic treatment were randomly assigned to receive one of three regimens: tremelimumab (300 mg, one dose) plus durvalumab (1500 mg every 4 weeks; STRIDE), durvalumab (1500 mg every 4 weeks), or sorafenib (400 mg twice daily). The primary objective was overall survival for STRIDE versus sorafenib.
View Article and Find Full Text PDFBackground & Aims: IMbrave150 demonstrated that atezolizumab plus bevacizumab led to significantly improved overall survival (OS) and progression-free survival (PFS) compared with sorafenib in patients with unresectable hepatocellular carcinoma at the primary analysis (after a median 8.6 months of follow-up). We present updated data after 12 months of additional follow-up.
View Article and Find Full Text PDFImportance: Ensartinib, an oral tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK), has shown systemic and central nervous system efficacy for patients with ALK-positive non-small cell lung cancer (NSCLC).
Objective: To compare ensartinib with crizotinib among patients with advanced ALK-positive NSCLC who had not received prior treatment with an ALK inhibitor.
Design, Setting, And Participants: This open-label, multicenter, randomized, phase 3 trial conducted in 120 centers in 21 countries enrolled 290 patients between July 25, 2016, and November 12, 2018.
Importance: Administration of pembrolizumab plus concurrent chemoradiation therapy (cCRT) may provide treatment benefit to patients with locally advanced, stage III non-small cell lung cancer (NSCLC).
Objective: To evaluate treatment outcomes and safety of pembrolizumab plus cCRT in stage III NSCLC.
Design, Setting, And Participants: The phase 2, nonrandomized, 2-cohort, open-label KEYNOTE-799 study enrolled patients between November 5, 2018, and July 31, 2020, from 52 academic facilities and community-based institutions across 10 countries.
Background: Understanding patients' experience of cancer treatment is important. We aimed to evaluate patient-reported outcomes (PROs) with atezolizumab plus bevacizumab versus sorafenib in patients with advanced hepatocellular carcinoma in the IMbrave150 trial, which has already shown significant overall survival and progression-free survival benefits with this combination therapy.
Methods: We did an open-label, randomised, phase 3 trial in 111 hospitals and cancer centres across 17 countries or regions.
Background: Many cancer patients undergo sophisticated laboratory testing, which requires proper interpretation and interaction between different specialists.
Case Presentation: We describe a patient with an extensive family history of cancer, who was diagnosed with bilateral breast cancer and two lung cancer lumps by the age of 40 years. She submitted a lung cancer specimen to a genetic profiling service, which reported the presence of the EGFR mutation (a combination of G719S and L833V substitutions) and the TP53 с.
Background: Health-related quality of life (HRQoL) is an important outcome measure and prognostic indicator in hepatocellular carcinoma (HCC). KEYNOTE-240 (NCT02702401) assessed the efficacy and safety of pembrolizumab plus best supportive care (BSC) versus placebo plus BSC in patients with HCC who previously received sorafenib. This study presents the results of a prespecified exploratory analysis of patient-reported outcomes.
View Article and Find Full Text PDFBackground: The combination of atezolizumab and bevacizumab showed encouraging antitumor activity and safety in a phase 1b trial involving patients with unresectable hepatocellular carcinoma.
Methods: In a global, open-label, phase 3 trial, patients with unresectable hepatocellular carcinoma who had not previously received systemic treatment were randomly assigned in a 2:1 ratio to receive either atezolizumab plus bevacizumab or sorafenib until unacceptable toxic effects occurred or there was a loss of clinical benefit. The coprimary end points were overall survival and progression-free survival in the intention-to-treat population, as assessed at an independent review facility according to Response Evaluation Criteria in Solid Tumors, version 1.
Background: There are no systemic treatments for patients with hepatocellular carcinoma (HCC) whose disease progresses during sorafenib treatment. We aimed to assess the efficacy and safety of regorafenib in patients with HCC who have progressed during sorafenib treatment.
Methods: In this randomised, double-blind, parallel-group, phase 3 trial done at 152 sites in 21 countries, adults with HCC who tolerated sorafenib (≥400 mg/day for ≥20 of last 28 days of treatment), progressed on sorafenib, and had Child-Pugh A liver function were enrolled.