National Cancer Center Hospital East

The administration of bevacizumab, ramucirumab, and aflibercept increases the incidence of hypertension; however, the risk of discontinuation of cancer therapy due to hypertension from these medications remains unclear. A systematic review and meta-analysis were conducted to assess the incidence and risk of hypertension associated with bevacizumab, ramucirumab, and aflibercept, as well as the risk of treatment discontinuation due to hypertension. Phase III randomized controlled trials (RCTs) of these therapies published through November 5, 2024, were identified through searches in PubMed, Cochrane Library, and Web of Science databases. The meta-analysis included 57 RCTs comprising 34,145 patients who received bevacizumab, ramucirumab, or aflibercept. The overall incidence of hypertension was 28% (95% confidence interval [CI]: 22-34%) for all-grade hypertension and 9% (95% CI: 7-11%) for grade ≥3 hypertension. Compared to control groups, treatment with these agents was associated with an increased risk of all-grade hypertension (odds ratio [OR]: 4.5; 95% CI: 3.7-5.5) and grade ≥3 hypertension (OR: 5.0; 95% CI: 4.0-6.3). The incidence of treatment discontinuation due to hypertension was 1% (95% CI: 1-2%), with a risk difference of 1.60% (95% CI: 0.76-2.38). VEGF inhibitor therapy-induced hypertension has been suggested to increase the risk of cancer treatment discontinuation. Therefore, careful monitoring and management of blood pressure in patients receiving these agents is essential.

Protein phosphorylation is a central post-translational modification regulating cellular signaling, frequently dysregulated in cancer. Mass spectrometry (MS)-based phosphoproteomics has emerged as a powerful approach to systematically profile phosphorylation events, thereby revealing aberrant kinase activity and therapeutic vulnerabilities that are not captured by genomic or transcriptomic analyses. Recent advances across the workflow-including optimized sample preparation and phosphopeptide enrichment, isotope- or label-free quantitative strategies, high-resolution mass spectrometry platforms, specialized algorithms for site identification and quantification, and integrative informatics analyses-have enabled the detection of tens of thousands of phosphorylation sites even from small clinical specimens. These developments have facilitated the characterization of signaling pathways across diverse cancer types, leading to the identification of targetable kinases and informing therapeutic strategies. In this review, we highlight studies that employed phosphoproteomic analyses of clinical specimens or patient-derived cancer cells to delineate signaling characteristics and to propose and validate therapeutic targets. Collectively, MS-based phosphoproteomics is poised to become a cornerstone of precision oncology. By enabling comprehensive and quantitative mapping of phosphorylation events, this technology allows mechanistic dissection of cancer signaling pathways and uncovers therapeutic vulnerabilities that may be exploited with targeted agents.

Minimal residual disease (MRD) detection using liquid biopsy is an emerging tool for risk stratification and monitoring for recurrence in resected early stage NSCLC. There is increasing need for clear guidance on its optimal clinical implementation. The Asian Thoracic Oncology Research Group (ATORG) convened a multidisciplinary panel of 27 experts to develop a consensus statement on the clinical application of circulating tumor DNA-based MRD testing in early stage resected NSCLC, using a structured Delphi methodology. Statements were organized into the following broad thematic domains: assay validity and standardization; harmonization in research and trials; clinical application; challenges in implementation; consensus recommendations; infrastructure for regional MRD adoption; and roadmap for pragmatic trials. A total of 23 position statements were developed, of which all except one achieved strong consensus. The consensus highlighted the need to define minimum analytical performance thresholds for MRD assays, improve standardization of reporting metrics, and clear guidelines for pre-analytical handling. Harmonization of blood sampling time points and terminology across clinical trials is also essential to confirm the prognostic value of MRD assays. Although current MRD assays demonstrate high specificity and positive predictive value, variable sensitivity precludes routine use for adjuvant therapy de-escalation outside clinical trials. Broader access, sustainable funding, ongoing consensus building, and collaborative real-world data generation are also critical to support clinical implementation and adoption. Future clinical trials must account for the distinct biology and changing standards of care associated with different driver genes. These consensus recommendations provide a pragmatic framework to guide the responsible integration of MRD testing into clinical research and practice.

Magrolimab (ONO-7913) is an anti-cluster of differentiation 47 (CD47) monoclonal antibody. This was a phase 1, open-label, uncontrolled, dose-escalation study that assessed the tolerability and safety of intravenous magrolimab (priming dose: 1 mg/kg; maintenance dose: 20 mg/kg [Cohort 1] or 30 mg/kg [Cohort 2]; 28-day treatment cycle) in Japanese adult patients with histologically or cytologically confirmed advanced or metastatic solid tumors, ≥ 1 measurable lesion, an Eastern Cooperative Oncology Group performance score of 0–1, and an expected survival ≥ 3 months. Seven patients were enrolled and received magrolimab (Cohort 1, n = 4; Cohort 2, n = 3) with the median follow-up of 170.0 (34–491) days. All 7 patients discontinued the magrolimab monotherapy, and 4 (57.1%) patients completed the study as per the protocol. No dose-limiting toxicities were observed in both cohorts, and the maximum tolerated dose was not reached. All patients experienced treatment-emergent adverse events (TEAEs) but not any serious adverse events, TEAEs leading to treatment discontinuation or interruption, or TEAE-related deaths. No complete or partial responses occurred, while the disease control rate was 42.9% (best overall response: stable disease, n = 3; disease progression, n = 3; not evaluable, n = 1). Magrolimab was well tolerated in Japanese patients with advanced or metastatic solid tumors. Trial registration: NCT04403308, submitted on May 21, 2020.

BackgroundA Japanese phase 2 trial of encorafenib plus binimetinib met the primary endpoint of the centrally assessed objective response rate in patients with unresectable BRAF V600E-mutated thyroid cancer. Consequently, encorafenib plus binimetinib has been approved in Japan. We present the health-related quality of life (HR-QoL) outcomes from the trial.MethodsThe multicenter, open-label, uncontrolled phase 2 trial enrolled patients with unresectable locally advanced or metastatic BRAF V600E-mutated thyroid cancer. HR-QoL score, one of the secondary endpoints, was assessed using the EORTC QLQ-C30 and QLQ-THY34 at baseline and during follow-up. The minimal important change (MIC) threshold was set at 10 points.ResultsWe enrolled 22 patients with BRAF V600E-mutated thyroid cancer. The median follow-up was 11.5 months. Completion rates for the questionnaires were 100% (22 of 22 patients) at baseline and 68% (15 of 22) at week 20. Until week 20, changes from baseline were below MIC at most time points in 29 of all 32 domains in QLQ-C30 and QLQ-THY34. In the other 3 domains, patients showed tendencies toward improvement (social support and appetite loss) or deterioration (joint pain) for consecutive time points. Patients with anaplastic thyroid cancer showed tendencies toward improvement for swallowing, restlessness, body image, and discomfort in the head and neck, from the first assessment after the initial treatment.ConclusionThe combination therapy of encorafenib plus binimetinib for unresectable BRAF V600E-mutated thyroid cancer was associated with generally maintained HR-QoL. Considering the efficacy and safety data from the trial, the regimen may provide clinical benefits while maintaining HR-QoL.

Abstract Introduction Maintaining dose intensity is essential for the efficacy of adjuvant S-1 chemotherapy in gastric cancer. Although pharmacist interventions can reduce toxicity and improve adherence, multicenter evidence regarding their impact on dose maintenance is limited. Aim This study aimed to evaluate the impact of continuous pharmacist intervention on treatment completion and relative performance (RP) value in patients receiving adjuvant S-1 chemotherapy for gastric cancer. Methods This multicenter retrospective study analysed 225 patients across 12 institutions, categorised into continuous intervention (n=97) and non-continuous intervention (n=128) groups. Continuous intervention was defined as systematic monitoring and management for at least 50% of the treatment duration. Inverse probability of treatment weighting adjusted for baseline covariates. The primary and secondary endpoints were the eight-cycle completion rate and the RP value, respectively. Results Eight-cycle completion rate did not differ significantly between the continuous and non-continuous intervention groups (53.0% vs. 55.2%, p = 0.775), nor did the frequency of treatment modification events, including discontinuation or dose reduction. However, the RP value was significantly higher in the continuous intervention group than in the non-continuous intervention group (73.7% vs. 64.9%, p = 0.038), a finding robustly supported by sensitivity analysis between these two groups (75.1% vs. 61.1%, p = 0.0008). The continuous group maintained a high intervention rate (89.1%) throughout the final cycle, providing significantly more supportive care interventions than the non-continuous intervention group (53.2% vs. 4.9%, p < 0.001). Conclusion Although continuous pharmacist intervention did not improve the binary completion rate, it was essential for maintaining RP values above the clinically essential 70% threshold through proactive toxicity management and dynamic dose optimization. These findings suggest that systematic pharmaceutical care contributes significantly to ensuring the quality and intensity of adjuvant chemotherapy.