Human epidermal growth factor receptor 2 (HER2) mutations in non-small cell lung cancer (NSCLC) are associated with aggressive disease and poor prognosis. Improved understanding of patient characteristics is vital to advance personalized treatment and improve outcomes. In this structured protocol-based targeted literature review, we assessed the epidemiology and ‘real-world’ outcomes in patients with HER2-mutant NSCLC by region, and by mutation category (tyrosine kinase domain [TKD] and non-TKD). Across 64 studies, the frequency of HER2 mutations ranged from 1
To investigate the frequency of visually ill-demarcated small pancreatic ductal adenocarcinomas (PDACs) and compare their clinicopathologic and MRI characteristics with those of well-demarcated tumors. This multicenter retrospective study enrolled 210 patients with surgically confirmed small PDACs (≤ 20 mm) who underwent preoperative unenhanced MRI. Clinical and pathological data were collected. Two radiologists independently evaluated the following MRI features: (a) tumor delineation (well-demarcated or ill-demarcated), (b) tumor signal intensity, and (c) secondary signs, including distal parenchymal signal intensity, parenchymal atrophy, main pancreatic duct (MPD) stenosis and dilatation, and small retention cyst. Clinicopathologic features and MRI findings were compared between well-demarcated and ill-demarcated PDACs using the Mann–Whitney and Fisher’s exact tests. Multivariate logistic regression analysis was performed to identify independent factors associated with ill-demarcated PDAC. Visually ill-demarcated tumors accounted for 46.7
Treatment-free remission (TFR) is an emerging goal for patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKI). However, long-term TFR durability in real-world settings remains understudied. The J-SKI study, a large observational study, was conducted to evaluate long-term TFR outcomes in Japanese patients with CML. This interim analysis included 795 eligible patients from the prospective (n = 283) and retrospective (n = 512) cohorts. With a median follow-up of 32 months (range 0.8–168) after TKI discontinuation, the 5-year TFR rate was 65.2
3025 Background: Safety and efficacy of HER2 tyrosine kinase inhibitor (TKI) and anti-HER2 antibody-drug conjugate (ADC) in HER2-mutant solid tumors have not been investigated. Methods: Mobocertinib, a potent HER2 TKI plus T-DM1, an anti-HER2 ADC was evaluated in this phase I study. In a dose-finding cohort (phase Ia, pIa), the maximum tolerated dose was estimated in patients (pts) irrespective of HER2 mutational status. To further establish safety and evaluate preliminary efficacy, additional pts with HER2 mutations were enrolled in a dose-expansion cohort (phase Ib, pIb). Mobocertinib of 80, 120 to 160 mg was orally administered with intravenous T-DM1 3.6 mg/kg every 3 weeks. The primary endpoint was to determine the recommended dose (RD) (pIa), and to evaluate the confirmed objective response rate (ORR) (pIb). Results: Between Nov 2022 and Jun 2023, a total of 28 pts, 6 in the pIa and 22 in the pIb were enrolled to this study (14 NSCLC; 4 cervical; 2 duodenal papilla; 2 pancreatic, median follow-up, 6.4 mo [range, 1.9 to 12.9 mo]). The median age was 54 (range, 40-84) years, 17 pts were female. Among 27 pts with HER2-mutant tumors, mutations in kinase domain were most common (66.7%). In the pIa cohort, 3 DLTs were observed with mobocertinib 120 mg, including grade 3 thrombocytopenia, grade 4 acute kidney injury, and drug withdrawal due to nausea and anorexia, while there was no DLT with 80 mg. The RD was therefore determined to be mobocertinib 80 mg plus T-DM1 3.6 mg/kg. Among 22 pts in the pIb, grade ≥ 3 AE occurred in 72.7% of pts; the common events (>5%) being thrombocytopenia (50.0%), diarrhea (13.6%), and anorexia (13.6%). No interstitial lung disease/pneumonitis was observed. The ORR was 28.6%, the disease control rate (DCR) was 71.4%, and median progression-free survival (mPFS) was 3.2 mo (95% CI 1.6, 6.1) in the pIb. In 27 pts with HER2 mutations across all cohorts, the ORR was 42.3%, the DCR was 76.9%, and mPFS was 4.3 mo (95% CI 2.7, 6.7). Additionally, in 13 pts with HER2-mutant NSCLC including those who had developed resistance to trastuzumab deruxtecan, the ORR was 53.8%, the DCR was 84.6%, and mPFS was 6.1 mo (95% CI 2.9, 6.3). Conclusions: The RD of this study treatment is mobocertinib 80 mg plus T-DM1 3.6 mg. Combination therapy of HER2 TKI and HER2 ADC demonstrated feasibility and potential efficacy for HER2-mutant solid tumors. Clinical trial information: 2051220070 .
INTRODUCTION:In real-world practice in Japan, standard treatment for metastatic hormone-naïve prostate cancer (mHNPC) is androgen deprivation therapy (ADT), administered as monotherapy, combined androgen blockade (CAB), ADT plus androgen receptor pathway inhibitors (ARPIs), or ADT plus docetaxel. In a previous interim analysis of the large-scale, longitudinal, multicentre, J-ROCK registry study of real-world clinical and patient-reported outcomes, ADT plus ARPI or ADT plus docetaxel was used more frequently than ADT/CAB in patients (aged ≥ 20 years) with newly diagnosed LATITUDE-criteria high-risk mHNPC. METHODS:This post hoc analysis of the J-ROCK study evaluated prostate-specific antigen (PSA) response, progression-free survival (PFS), time to castration-resistant prostate cancer (CRPC), overall survival (OS) and safety in patients with high-risk mHNPC who received ADT/CAB (cohort 1) or ADT plus ARPI (cohort 2B) in subgroups were defined according to the following known prognostic factors at baseline: age, Gleason Grade Group (GGG), alkaline phosphatase (ALP), hemoglobin (Hb) and lactate dehydrogenase (LDH). RESULTS:This analysis included 947 evaluable patients (371 in cohort 1 and 576 in cohort 2B). PSA response rates remained similar among age and GGG subgroups in both cohorts, but were reduced in cohort 2B patients with elevated ALP, low Hb, and elevated LDH. Time to CRPC and OS were longer in cohort 2B than in cohort 1, regardless of prognostic factors. Among patients with poor prognosis (older, high GGG, low Hb, elevated LDH), OS decline occurred earlier in cohort 1 versus cohort 2B. A trend towards a plateau in the time to CRPC curve was observed in both cohorts, even in patients with poor prognosis. Safety data were not affected by prognostic factors or treatment. CONCLUSIONS:These findings suggest that novel ADT plus ARPI regimens for LATITUDE-criteria high-risk mHNPC may improve real-world outcomes compared with ADT monotherapy or CAB, particularly among patients with poor prognosis.
