PALOMA-3 clinical trial: is there a significant benefit in overall survival for breast cancer? Is it worth it?

Adashek, Jacob J.; Aguiar, Pedro Nazareth; Castelo‐Branco, Pedro; Lopes, Gilberto; Mello, Ramon Andrade De

doi:10.2217/fon-2019-0044

Cited by 5 publications

(3 citation statements)

References 17 publications

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“…[5,53,55,56] Still the question that arises is whether or not combining drug A with drug B is better than sequentially using drug A followed by drug B. Some studies, such as those showing modest efficacy of single-agent EGFR inhibitors in gastric cancer [57] and single-agent CDK inhibitors in breast cancer [58,59], while combinations such as those of CDK inhibitors with anti-estrogens are effective, [60] indicate that drug combinations are needed from the beginning (Table 2). But the question of combination versus sequential therapy still needs answering on a larger scale level.…”

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

Cancer: slaying the nine-headed Hydra

Adashek¹,

Subbiah²,

Westphalen³

et al. 2023

Annals of Oncology

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Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

Cancer: slaying the nine-headed Hydra

Adashek¹,

Subbiah²,

Westphalen³

et al. 2023

Annals of Oncology

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“…Some oncological drugs that lack efficacy as single agents could produce durable responses when combined with other compounds with a different mechanism of action [159,160]. For example, some studies show the modest efficacy of single-agent EGFR inhibitors in gastric cancer [158] and single-agent CDK (cyclin-dependent kinase) inhibitors in breast cancer [161,162]. Although, combinations such as those of CDK inhibitors with antiestrogens are effective, indicating that drug combinations are needed to enhance the activity [163].…”

Section: Combinations N-of-1mentioning

confidence: 99%

Agnostic Approvals in Oncology: Getting the Right Drug to the Right Patient with the Right Genomics

et al. 2023

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(1) Background: The oncology field has drastically changed with the advent of precision medicine, led by the discovery of druggable genes or immune targets assessed through next-generation sequencing. Biomarker-based treatments are increasingly emerging, and currently, six tissue-agnostic therapies are FDA-approved. (2) Methods: We performed a review of the literature and reported the trials that led to the approval of tissue-agnostic treatments and ongoing clinical trials currently investigating novel biomarker-based approaches. (3) Results: We discussed the approval of agnostic treatments: pembrolizumab and dostarlimab for MMRd/MSI-H, pembrolizumab for TMB-H, larotrectinib and entrectinib for NTRK-fusions, dabrafenib plus trametinib for BRAF V600E mutation, and selpercatinib for RET fusions. In addition, we reported novel clinical trials of biomarker-based approaches, including ALK, HER2, FGFR, and NRG1. (4) Conclusions: Precision medicine is constantly evolving, and with the improvement of diagnostic tools that allow a wider genomic definition of the tumor, tissue-agnostic targeted therapies are a promising treatment strategy tailored to the specific tumor genomic profile, leading to improved survival outcomes.

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“…Each combination therapy has demonstrated a significant prolongation of progression-free survival (PFS) compared with hormonal monotherapy [1,[5][6][7]. In addition, CDK4/6 inhibitors showed a statistically significant prolongation of overall survival (OS) as a secondary endpoint when used in combination with fulvestrant [8][9][10][11]. However, there is no standard care for cases of disease progression after endocrine-based therapy with a CDK4/6 inhibitor.…”

Section: Introductionmentioning

confidence: 99%

Phase 1 trial of entinostat as monotherapy and combined with exemestane in Japanese patients with hormone receptor-positive advanced breast cancer

et al. 2021

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Background Entinostat is an oral inhibitor of class I histone deacetylases intended for endocrine therapy-resistant patients with hormone receptor-positive (HR+) advanced or metastatic breast cancer (BC). We examined the safety, efficacy, and pharmacokinetics of entinostat monotherapy and combined entinostat/exemestane in Japanese patients. Methods This phase 1 study (3 + 3 dose-escalation design) enrolled postmenopausal women with advanced/metastatic HR+ BC previously treated with nonsteroidal aromatase inhibitors. Dose-limiting toxicities (DLTs) of entinostat monotherapy (3 mg/qw, 5 mg/qw, or 10 mg/q2w) and entinostat+exemestane (5 mg/qw + 25 mg/qd) were assessed. Pharmacokinetics, lysine acetylation (Ac-K), and T-cell activation markers were measured at multiple time points. Results Twelve patients were enrolled. No DLTs or grade 3–5 adverse events (AEs) occurred. Drug-related AEs (≥ 2 patients) during DLT observation were hypophosphatemia, nausea, and platelet count decreased. Six patients (50%) achieved stable disease (SD) for ≥ 6 months, including one treated for > 19 months. Median progression-free survival was 13.9 months (95% CI 1.9–not calculable); median overall survival was not reached. Area under the plasma concentration-time curve and Ac-K in peripheral blood CD19+ B cells increased dose-proportionally. The changing patterns of entinostat concentrations and Ac-K levels were well correlated. T-cell activation markers increased over time; CD69 increased more in patients with SD ≥ 6 months vs. SD < 6 months. Conclusions Entinostat monotherapy and combined entinostat/exemestane were well tolerated in Japanese patients, with no additional safety concerns compared with previous reports. The correlation between pharmacokinetics and Ac-K in peripheral blood CD19+ B cells, and also T-cell activation markers, merits further investigation. Trial registration JAPIC Clinical Trial Information, JapicCTI-153066. Registered 12 November 2015. ClinicalTrials.gov, NCT02623751. Registered 8 December 2015.

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PALOMA-3 clinical trial: is there a significant benefit in overall survival for breast cancer? Is it worth it?

Cited by 5 publications

References 17 publications

Cancer: slaying the nine-headed Hydra

Cancer: slaying the nine-headed Hydra

Agnostic Approvals in Oncology: Getting the Right Drug to the Right Patient with the Right Genomics

Phase 1 trial of entinostat as monotherapy and combined with exemestane in Japanese patients with hormone receptor-positive advanced breast cancer

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