A Phase I Study of the Pharmacokinetics and Safety of Ipatasertib, an Akt Inhibitor in Chinese Patients With Locally Advanced or Metastatic Solid Tumors.

Purpose: Ipatasertib is a selective inhibitor of Akt, a frequently activated protein kinase that plays a critical role in human cancers. The current clinical trial aimed to assess the pharmacokinetic properties, safety, and tolerability of ipatasertib administered to Chinese patients with locally advanced or metastatic solid tumors.

Methods: A Phase I, single-arm, open-label study was performed in Chinese patients with locally advanced or metastatic solid tumors for whom standard therapy either does not exist or has proven ineffective.

Patient-reported quality of life in Asian patients with ER+/HER2- advanced breast cancer treated with palbociclib plus letrozole in the PALOMA-4 trial.

Background: Palbociclib plus an aromatase inhibitor is approved for treatment of patients with ER+/HER2- advanced breast cancer (ABC). In the PALOMA-4 trial, adding palbociclib to letrozole prolonged median progression-free survival in Asian women with ER+/HER2- ABC. Here, we report patient-reported outcomes (PROs) from PALOMA-4.

Clinicopathological characteristics, evolution, and treatment outcomes of hormone receptor-negative/HER2-low metastatic breast cancer: a pooled analysis of individual patient data from three prospective clinical trials.

Objective: With the approval of trastuzumab deruxtecan for the treatment of unresectable/metastatic HER2-low breast cancer, human epidermal growth factor receptor 2 (HER2)-low has emerged as a clinically actionable biomarker. There is an urgent need for a deeper understanding of HER2-low breast cancer patients. Therefore, this study was conducted to explore the clinicopathological characteristics, the evolution of HER2-low status, and its impact on the prognosis of hormone receptor (HoR)-negative/HER2-low metastatic breast cancer (MBC) patients.

Chaperonin-containing TCP1 subunit 6A inhibition via TRIM21-mediated K48-linked ubiquitination suppresses triple-negative breast cancer progression through the AKT signalling pathway.

Background: Triple-negative breast cancer (TNBC) is distinguished by a significant likelihood of distant recurrence and an unfavourable prognosis. However, the underlying molecules and mechanisms have not been fully elucidated.

Methods: We investigated the expression profile and clinical relevance of chaperonin-containing TCP1 subunit 6A (CCT6A) in TNBC.

Entrectinib versus crizotinib in Asian patients with ROS1-positive non-small cell lung cancer: A matching-adjusted indirect comparison.

Objectives: Entrectinib and crizotinib are the only ROS proto-oncogene 1 receptor (ROS1) tyrosine kinase inhibitors available for most Asian patients. Their efficacy has neither been compared directly in clinical trials in patients with ROS1-positive non-small cell lung cancer (NSCLC), nor indirectly in Asian populations. Thus, we aimed to provide comparative evidence of the efficacy and safety of entrectinib and crizotinib for Asian patients with advanced or metastatic ROS1-positive NSCLC.

Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer.

Background: Outcomes in patients with hormone receptor-positive metastatic breast cancer worsen after one or more lines of endocrine-based therapy. Trastuzumab deruxtecan has shown efficacy in patients with metastatic breast cancer with low expression of human epidermal growth factor receptor 2 (HER2) after previous chemotherapy.

Methods: We conducted a phase 3, multicenter, open-label trial involving patients with hormone receptor-positive metastatic breast cancer with low HER2 expression (a score of 1+ or 2+ on immunohistochemical [IHC] analysis and negative results on in situ hybridization) or ultralow HER2 expression (IHC 0 with membrane staining) who had received one or more lines of endocrine-based therapy and no previous chemotherapy for metastatic breast cancer.

Site-specific therapy guided by a 90-gene expression assay versus empirical chemotherapy in patients with cancer of unknown primary (Fudan CUP-001): a randomised controlled trial.

Background: Empirical chemotherapy remains the standard of care in patients with unfavourable cancer of unknown primary (CUP). Gene-expression profiling assays have been developed to identify the tissue of origin in patients with CUP; however, their clinical benefit has not yet been demonstrated. We aimed to evaluate the efficacy and safety of site-specific therapy directed by a 90-gene expression assay compared with empirical chemotherapy in patients with CUP.

Liposomal irinotecan (HR070803) in combination with 5-fluorouracil and leucovorin in patients with advanced solid tumors: a phase 1b dose-escalation and expansion study.

This phase 1b study aimed to evaluate the dose-limiting toxicity (DLT), maximum tolerated dose (MTD), pharmacokinetics, and preliminary efficacy of HR070803, a novel nanoliposomal formulation of irinotecan, in combination with 5-fluorouracil and leucovorin in patients with pretreated advanced solid tumors. This study consisted of dose-escalation and expansion stages. Dose escalation was performed with a traditional 3 + 3 design; patients received intravenous infusion of HR070803 from 60 to 80 mg/m, followed by leucovorin (200 mg/m) and 5-fluorouracil (2000 mg/m) every 2 weeks.

Emerging roles of tripartite motif family proteins (TRIMs) in breast cancer.

Breast cancer (BC) is the most common malignant tumor worldwide. Despite enormous progress made in the past decades, the underlying mechanisms of BC remain further illustrated. Recently, TRIM family proteins proved to be engaged in BC progression through regulating various aspects.

BOLERO-5: a phase II study of everolimus and exemestane combination in Chinese post-menopausal women with ER + /HER2- advanced breast cancer.

Background: The global BOLERO-2 trial established the efficacy and safety of combination everolimus (EVE) and exemestane (EXE) in the treatment of estrogen receptor positive (ER +), HER2-, advanced breast cancer (ABC). BOLERO-5 investigated this combination in a Chinese population (NCT03312738).

Methods: BOLERO-5 is a randomized, double-blind, multicenter, placebo controlled, phase II trial comparing EVE (10 mg/day) or placebo (PBO) in combination with EXE (25 mg/day).

6th and 7th International consensus guidelines for the management of advanced breast cancer (ABC guidelines 6 and 7).

This manuscript describes the Advanced Breast Cancer (ABC) international consensus guidelines updated at the last two ABC international consensus conferences (ABC 6 in 2021, virtual, and ABC 7 in 2023, in Lisbon, Portugal), organized by the ABC Global Alliance. It provides the main recommendations on how to best manage patients with advanced breast cancer (inoperable locally advanced or metastatic), of all breast cancer subtypes, as well as palliative and supportive care. These guidelines are based on available evidence or on expert opinion when a higher level of evidence is lacking.

Tucidinostat plus exemestane for postmenopausal patients with advanced, hormone receptor-positive breast cancer: a long-term safety and overall survival update from the randomised, double-blind, placebo-controlled, phase 3 trial.

Background: The ACE study previously demonstrated that tucidinostat (chidamide), a subtype-selective histone deacetylase (HDAC) inhibitor, plus exemestane significantly improved progression-free survival (PFS) in advanced hormone receptor-positive (HR) breast cancer patients with a manageable safety profile. The analysis of long-term safety and overall survival (OS) is presented here.

Methods: ACE is a randomized, double-blind, placebo-controlled, phase 3 trial comparing tucidinostat 30 mg/twice weekly plus exemestane 25 mg/day versus placebo plus exemestane 25 mg/day in postmenopausal patients with advanced, HR breast cancer.

Comprehensive analysis of cancer of unknown primary and recommendation of a histological and immunohistochemical diagnostic strategy from China.

Background: Previous studies on cancer of unknown primary (CUP) mainly focus on treatment and prognosis in western populations and lacked clinical evaluation of different IHC markers, so this study aimed to evaluate characteristics of CUP and recommend a diagnostic strategy from a single center in China.

Methods And Results: Data of 625 patients with CUP were retrospectively collected and reviewed. The patients ranged in age from 20 to 91 years, with a female-to-male ratio of 1.

HS-10352 in hormone receptor-positive, HER2-negative advanced breast cancer: A phase 1 dose-escalation trial.

Background: Approximately 40% of patients with hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) exhibit PIK3CA mutations.

Aims: This study aims to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of HS-10352, a selective PI3Kα inhibitor, in this patient population.

Materials And Methods: Conducted as a phase 1 dose-escalation trial, HS-10352 was administered orally once-daily (QD) at dose levels of 2, 4, 6, and 8 mg.

HER2-low heterogeneity between primary and paired recurrent/metastatic breast cancer: Implications in treatment and prognosis.

Background: With the largest sample size to date, the authors' objective was to investigate the incidence of primary-to-metastatic human epidermal growth factor 2 (HER2) conversion and the predictors for such conversion. Moreover, no previous studies have evaluated the prognosis of patients who have negative HER2 expression (HER2-0) versus low HER2 expression (HER2-low) when HER2 status was assessed based on all recurrent/metastatic lesions.

Methods: The authors included 1299 patients who had available HER2 status of primary breast tumors and paired recurrent/metastatic lesions at Fudan University Shanghai Cancer Center and West China Hospital.

Pretreatment F-FDG uptake heterogeneity may predict treatment outcome of combined Trastuzumab and Pertuzumab therapy in patients with metastatic HER2 positive breast cancer.

Objective: Intra-tumoral heterogeneity of F-fluorodeoxyglucose (F-FDG) uptake has been proven to be a surrogate marker for predicting treatment outcome in various tumors. However, the value of intra-tumoral heterogeneity in metastatic Human epidermal growth factor receptor 2(HER2) positive breast cancer (MHBC) remains unknown. The aim of this study was to evaluate F-FDG uptake heterogeneity to predict the treatment outcome of the dual target therapy with Trastuzumab and Pertuzumab(TP) in MHBC.

Pyrotinib plus capecitabine for trastuzumab-resistant, HER2-positive advanced breast cancer (PICTURE): a single-arm, multicenter phase 2 trial.

Background: Patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer and primary resistance to trastuzumab have a poor clinical outcome and lack good evidence to inform clinical decision. This study investigated the efficacy and safety of pyrotinib plus capecitabine in this population.

Methods: This phase 2 trial was conducted at 16 sites in China.