PURPOSE:Angiogenesis plays an essential role in neuroendocrine tumors (NETs). This study evaluates efficacy and safety of axitinib in extrapancreatic (ep)-NETs. PATIENTS AND METHODS:AXINET was an international, randomized, double-blind, placebo-controlled, phase II/III trial including patients age 18 years and older, with unresectable/metastatic G1-2 epNETs and up to two previous treatment lines. Patients were randomly assigned (1:1) to axitinib 5 mg or placebo, both orally twice a day, in combination with intramuscular octreotide long-acting release 30 mg once every 28 days until disease progression or unacceptable toxicity. Randomization was stratified by primary tumor site, Ki-67 index (≤5% or >5%), and time from diagnosis (> or ≤12 months). The primary end point was investigator-assessed progression-free survival (PFS). Efficacy was also assessed by a blinded independent central review (BICR). RESULTS:From October 2011 to May 2019, 256 patients were assigned to axitinib (n = 126) or placebo (n = 130). Investigator-assessed median PFS was 17.2 months (95% CI, 13.6 to 24.7) versus 13.1 months (95% CI, 10.9 to 18.6) in the axitinib and placebo groups, respectively (hazard ratio [HR], 0.86 [95% CI, 0.65 to 1.15]). The median BICR PFS was 16.6 months (95% CI, 13.5 to 24.2) versus 9.9 months (95% CI, 8.2 to 13.9) in the axitinib and placebo groups, respectively (HR, 0.71 [95% CI, 0.54 to 0.94], P = .017). Objective response rate (ORR) was significantly greater for axitinib per investigator assessment (17.5% v 4.6%; P = .001) and BICR (12.8% v 3.2%; P = .005). Most common grade ≥3 toxicities were hypertension (24.0% v 9.2%) and diarrhea (13.6% v 1.5%). CONCLUSION:Axitinib significantly increased PFS per BICR assessment and ORR both per investigator and BICR assessment compared with placebo, although the primary study end point was not met. Toxicity profile was manageable with no new safety concerns.
Background:Over the past decade, the treatment landscape for metastatic urothelial carcinoma (mUC) has improved significantly with the introduction of immunotherapy, targeted agents, and antibody-drug conjugates. The median overall survival (mOS) reached 36.7 months in cisplatin-eligible and 25.6 months in cisplatin-ineligible patients in the first-line setting and over 10 months post-platinum failure. However, liver metastases remain a known poor prognostic factor. Methods:We conducted a retrospective analysis of mUC patients treated at 79 global institutions. Two cohorts were defined: cohort 1 included patients who progressed after platinum-based therapy and received pembrolizumab, and cohort 2 included patients who received avelumab as maintenance therapy. Treatments were administered between 1 January 2016 and 31 October 2024. Results:Cohort 1 (n = 1,341) had an mOS of 17.5 months. Patients without liver metastases had significantly longer OS than those with liver involvement (20.1 vs. 9.4 months, p <0.001). Among patients with liver metastases, OS was 11.8 months in males vs. 5.8 months in females (p = 0.066). OS was longer in those with BMI ≥25 kg/m² (14.1 vs. 8.1 months, p = 0.028) and better ECOG-PS (ECOG 0: 17.0 months; ECOG 1: 9.8; ECOG ≥2: 3.1; p <0.001). Cohort 2 (n = 291) had an mOS of 25.8 months. Again, OS was longer in patients without liver metastases (27.0 vs. 16.4 months, p <0.001). Among those with liver involvement, OS was 14.7 months in males and 20.0 months in females (p = 0.310). Patients with BMI ≥25 had non-reached OS versus 17.1 months in those with lower BMI (p <0.001). ECOG-PS remained a strong prognostic factor (NR for ECOG 0; 14.7 months for ECOG 1; 4.6 months for ECOG ≥2, p <0.001). Conclusion:Liver metastases are associated with significantly reduced survival in patients with mUC receiving immunotherapy. However, both pembrolizumab and avelumab demonstrated improved outcomes compared with historical chemotherapy data. These findings underscore the need for personalized treatment strategies in high-risk subgroups.
The sustained improvement in cancer survival has highlighted the growing impact of cardiovascular toxicity related to anticancer therapies, which has become a leading cause of non-cancer morbidity and mortality. This position statement aims to provide a practical and standardized framework for the comprehensive management of cardiotoxicity in oncology patients from the perspective of Primary Care (PC) in Spain, acknowledging its pivotal role in prevention, early detection, risk stratification, and long-term follow-up. The document reviews the main forms of cardiovascular toxicity associated with systemic anticancer therapies, as well as local treatments such as thoracic radiotherapy, incorporating current definitions and recommendations from European and international guidelines. A structured model based on the oncology care continuum is proposed, encompassing the initial phase, active treatment, and survivorship, allowing cardiovascular surveillance to be tailored according to baseline risk, type of treatment, and clinical evolution. Special emphasis is placed on early cardiovascular risk assessment, proactive optimization of cardiovascular risk factors and comorbidities, and the establishment of clear referral and coordination pathways between PC, Oncology, Hematology and Cardiology. The central role of PC in the follow-up of long-term cancer survivors is also highlighted, as this growing population remains at risk of late cardiovascular complications that may persist or increase over time. This position statement seeks to promote coordinated, equitable, and patient-centered care, reducing clinical variability and improving cardiovascular outcomes and quality of life for oncology patients within the National Health System.
Real-world data are essential for understanding treatment-related toxicities in haematology, but traditional analyses are limited by data access, sharing constraints, and reduced data granularity. Emerging digital health technologies (DHTs), such as electronic patient-reported outcomes and wearable devices, can be used to capture continuous, patient-generated data not reliably captured by current post-marketing toxicity assessments. Artificial intelligence, synthetic data, and digital twins can be used to predict and simulate toxicity at a much larger scale beyond the capacity of traditional methodologies. These emerging DHTs could overcome barriers, such as data fragmentation and lack of harmonisation, between existing real-world toxicity data sources. However, they also come with new challenges, including data quality and interpretability, integration into existing clinical workflows, privacy protection, and data governance. Developing and implementing them in partnership with patients, clinicians, payers, and regulators is necessary to maximise their impact in both individual patient and population-level clinical care.
