Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy represent the standard of care for hormone receptor-positive (HR+), HER2-negative metastatic breast cancer (mBC). While clinical trials established their efficacy, real-world evidence on safety, dose adjustments, and outcomes remains limited. We conducted a prospective observational study including patients with HR+/HER2- mBC treated with palbociclib, ribociclib, or abemaciclib across three oncology units between 2019 and 2024. Data on adverse events, dose modifications, progression-free survival (PFS), and overall survival (OS) were collected and analyzed. Adverse events were reported in 77.5% of patients. Neutropenia was the most frequent adverse event with palbociclib and ribociclib, while diarrhea and hepatic toxicity predominated with abemaciclib. Pulmonary toxicity occurred in 19.1% of abemaciclib-treated patients, often in those previously irradiated. Median PFS and OS were 26.4 and 31.1 months, respectively. The occurrence of grade 3-4 adverse events correlated with improved OS (37.1 vs. 23.0 months, P  < 0.001). Dose reductions, required in more than 60% of patients, did not compromise efficacy; instead, they were associated with longer PFS and OS. Conversely, treatment discontinuation predicted worse outcomes. In real-world practice, CDK4/6i toxicities are frequent but manageable. Proactive toxicity management and timely dose adjustments are essential to sustain treatment benefit. Dose reductions may even improve outcomes, underscoring the value of individualized dosing strategies.

BACKGROUND:Concomitant medications may impair immune checkpoint inhibitor (ICI) activity through modulation of the gut microbiome and systemic immunity. While a medication-based risk model (drug score) has been validated in pan-cancer cohorts, evidence in advanced urothelial carcinoma (aUC) remains limited. This study assessed the association between concomitant medications and survival in patients receiving avelumab maintenance in the Meet-URO 25 cohort. METHODS:We retrospectively analyzed patients with aUC treated with avelumab maintenance in several Italian centers. The drug score assigned 1 point each for antibiotics and PPIs, and 2 points for corticosteroids ≥ 10 mg prednisone equivalent. Patients were classified as good (0), intermediate (1-2), or poor (3-4) risk. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier and Cox models. RESULTS:Among 251 patients (median age 72; 82% male), use of interfering medications was low. Drug score distribution was 76.5% good, 21.9% intermediate, and 1.6% poor risk. Median PFS was 8.0, 3.9, and 2.9 months, respectively; median OS was 27.6, 14.0, and 3.4 months. Drug score, ECOG performance status, and bone metastases were independent prognostic factors. CONCLUSIONS:The drug score showed significant prognostic value in aUC patients receiving avelumab maintenance, supporting its integration into risk stratification for ICI-treated UC.

Background:Enfortumab vedotin (EV), an antibody-drug conjugate targeting Nectin-4, has demonstrated efficacy in advanced urothelial carcinoma (UC) following platinum-based chemotherapy and immune checkpoint inhibitor (ICI) therapy. However, real-world evidence on its effectiveness and safety remains limited. Methods:We conducted a multicenter retrospective study across Italian oncology centers to evaluate EV in patients with metastatic UC (mUC) who had progressed after prior platinum-based chemotherapy and ICI. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. We also assessed prognostic factors, including a composite index (HERO score) based on baseline hemoglobin and neutrophil-to-lymphocyte ratio (NLR). Results:Fifty-three patients were included (median age 72 years; 41.5% ⩾75 years). The ORR was 34.0% (all partial responses), with a DCR of 58.5%. Median PFS and OS were 6.1 and 9.7 months, respectively. Multivariate analysis identified NLR ⩾ 4 and lung metastases as independent predictors of inferior PFS, while NLR ⩾ 4 remained independently associated with worse OS. Dose reductions and peripheral neuropathy were associated with improved outcomes. The HERO score significantly stratified patients by PFS and OS (p = 0.017 and p < 0.001, respectively). EV was generally well tolerated, with most adverse events being low-grade. Conclusion:In this real-world cohort, EV confirmed its efficacy and manageable safety profile in mUC. The HERO score may provide a simple tool for risk stratification in clinical practice, though prospective validation is needed.

In advanced urothelial carcinoma (UC), the prognostic impact of metastatic site and burden during avelumab maintenance therapy remains poorly defined. We performed a sub-analysis of the Italian multicenter retrospective–prospective observational study Meet-URO 25, including patients with advanced UC who received avelumab maintenance after disease control with first-line platinum-based chemotherapy. We assessed the association between metastatic site and number of metastatic sites at the start of avelumab and clinical outcomes, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). A total of 243 patients were included. Lymph nodes (79.0

ABSTRACT Cancer remains a major global public health problem. A key aspect of cancer care among survivors is sexual health. Cancer patients experience a range of sexual dysfunctions, including erectile dysfunction, vaginal dryness, dyspareunia, and reduced libido. Psychological symptoms such as anxiety, fatigue, and body image issues often exacerbate these problems, leading to impaired emotional and relational functioning. Despite their profound impact on quality of life, these concerns are not systematically addressed in routine cancer care. Oncosexology fits into this context, addressing the profound impact of cancer and its treatments on sexual health and intimacy. Objectives This narrative review provides an overview of the current evidence on sexual dysfunction in adult cancer patients, including psychosocial correlates and available interventions, to help clinicians understand the scope, challenges, and management strategies related to sexual health in oncology. Method The study was conducted by searching major scientific databases using search terms related to sexual health in cancer patients. Inclusion criteria were studies involving adult cancer patients, focusing on sexual health outcomes, therapeutic interventions, or care models, and published in peer‐reviewed journals. Articles were selected based on the relevance of their findings and the quality of their presentation. Results Data published in the literature show that sexual dysfunctions are common in cancer populations and often co‐occur with psychological problems such as anxiety, fatigue, and altered body image. Interventions range from pharmacological treatments to psychosocial and psychosexual counseling and multidisciplinary care models. The results also highlight that, despite the difficulties patients and healthcare providers encounter in communicating about these topics, multidisciplinary interventions can help reduce these dysfunctions. Conclusions Integrating sexual health into cancer care is essential to promoting overall well‐being and supporting long‐term survival. Further high‐quality, cancer‐specific research is needed to support evidence‐based, patient‐centered interventions across diverse cancer populations.

Biochemical recurrence after definitive local therapy for prostate cancer represents a heterogeneous clinical state, with patients exhibiting short prostate-specific antigen (PSA) doubling time at particularly high risk of metastatic progression and cancer-related mortality. Persistent androgen receptor signaling plays a central role in sustaining occult micrometastatic disease, providing a strong biological rationale for early therapeutic intervention. The phase III EMBARK trial demonstrated that intensification of androgen receptor pathway inhibition with enzalutamide, administered either in combination with androgen deprivation therapy or as monotherapy, significantly improves metastasis-free survival and delays disease progression in patients with high-risk biochemical recurrence, with an overall survival benefit observed for combination therapy. Importantly, EMBARK introduced a PSA-guided treatment-suspension strategy designed to reduce cumulative treatment exposure. These findings redefine high-risk biochemical recurrence as an actionable disease state and support the integration of enzalutamide-based approaches into contemporary prostate cancer treatment algorithms.

Systemic inflammatory indices have been proposed as prognostic biomarkers in several malignancies; however, their role in patients receiving avelumab maintenance for advanced urothelial carcinoma (aUC) remains poorly defined. This study aimed to evaluate the prognostic impact of inflammatory markers in this context and to develop a composite score for outcome stratification. We retrospectively analyzed patients with aUC who were treated with avelumab maintenance therapy. Systemic inflammatory markers - including the neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-eosinophil ratio (NER), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and the systemic immune-inflammation index (SII) - were collected at baseline and after treatment initiation (cycle 3), and changes from baseline to cycle three were analyzed (increase versus stability/decrease). Overall survival (OS), the primary endpoint, was evaluated using Kaplan-Meier and Cox models. A prognostic score was created from the multivariable analysis. Time-dependent Receiver operating characteristics (ROC) analysis was employed to evaluate model discrimination at 6, 12, and 24 months. The prognostic impact on disease control rate (DCR - secondary endpoint) was assessed using logistic regression and ROC curves. A total of 358 patients were included in the study. In the multivariable analysis, high NLR, high NER, low LMR, increasing NLR trend, bone and liver metastases were independently associated with worse OS. These variables were incorporated into a 0-6 point prognostic score, which demonstrated good discrimination (C-index 0.76; AUC at 6, 12, and 24 months: 0.87, 0.75, and 0.73, respectively). The score remained prognostic across subgroups and following sensitivity analyses. High LMR, low NER, the absence of liver metastases, and the absence of bone metastases were independently associated with higher DCR. A response-associated score combining these variables showed a decreasing DCR from 69% (score 0) to 25% (score 4). Baseline and dynamic inflammatory markers may serve as prognostic factors for OS in patients with aUC undergoing avelumab maintenance therapy. A composite score that integrates laboratory and clinical features could allow for clinically meaningful stratification of survival and response outcomes, with potential applications in clinical practice. However, a prospective evaluation is necessary.

Immune checkpoint inhibitor-related pneumonitis (CIP) is an uncommon but clinically relevant toxicity in renal cell carcinoma (RCC), where immune checkpoint inhibitors are frequently used either as dual immunotherapy or in combination with VEGF-targeted tyrosine kinase inhibitors. In RCC, CIP poses specific diagnostic challenges because respiratory symptoms and computed tomography findings may overlap with pulmonary metastases, infections, thromboembolic events, heart failure, and TKI-related lung toxicity. This review summarizes the incidence of CIP across pivotal RCC trials and real-world cohorts, compares its epidemiology with non-small cell lung cancer, and discusses clinical presentation, radiological patterns, differential diagnosis, and current management strategies. Particular attention is given to RCC-specific mechanisms, including immune-mediated alveolar injury, T cell activation, cytokine dysregulation, macrophage activation, GSDME-mediated pyroptosis, and the potential contribution of VEGF pathway inhibition to pulmonary inflammation. We also review risk factors, steroid-refractory disease, second-line immunosuppression, and the unresolved issue of ICI rechallenge after pneumonitis. A better understanding of these mechanisms and clinical features may improve early recognition, guide multidisciplinary management, and support safer use of immunotherapy-based combinations in patients with RCC.

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.

BackgroundCombination therapy with the PARP inhibitor niraparib and the androgen-receptor inhibitor abiraterone acetate plus prednisone (AAP) has recently shown improvement in radiographic progression-free survival (rPFS) in patients with metastatic castration-resistant prostate cancer (mCRPC) harboring homologous recombination repair (HRR) gene alterations, particularly BRCA1/2, in the phase III MAGNITUDE trial. Evidence outside clinical trials remains limited.MethodsWe retrospectively reviewed the clinical courses of five consecutive patients with HRR-mutated mCRPC treated with niraparib (200 mg once daily) plus abiraterone acetate (1000 mg once daily) and prednisone (5 mg twice daily) at our institution. Baseline characteristics, PSA kinetics (including time to PSA 50% decline), radiological responses, progression-free survival (PFS; defined as a composite clinical, radiological, and biochemical endpoint), overall survival (OS), and safety outcomes were assessed. All patients underwent radiological evaluation every three months, including contrast-enhanced CT of the chest and abdomen and bone scintigraphy. Tumor response was assessed according to RECIST 1.1 criteria for measurable disease.ResultsAll patients harbored pathogenic HRR gene alterations: somatic and/or germline BRCA1/2 (three BRCA2, two BRCA1), and one patient with concurrent PALB2. Median age at therapy initiation was 70 years (range 60–80). Three patients (Patients 1, 4, 5) achieved significant and sustained PSA declines (≥50%) and prolonged disease control, including elderly and frail individuals. Two patients (Patients 2, 3) exhibited early progression with limited clinical benefit, consistent with aggressive disease course. Median PFS varied widely across the cohort, reflecting heterogeneity of clinical phenotypes. Treatment was generally manageable; dose interruptions or reductions were required in selected cases, with no new safety signals observed.ConclusionsNiraparib–abiraterone demonstrated anti-tumor activity in a subset of HRR-mutated mCRPC patients, including elderly and frail individuals. However, the very small sample size, retrospective design, and absence of standardized rPFS assessment limit generalizability. These findings are primarily hypothesis-generating but align with prospective trial results and underscore the heterogeneity of HRR-mutated mCRPC, highlighting the need for individualized therapeutic strategies.

BackgroundAvelumab maintenance therapy is an established therapeutic approach for patients with advanced urothelial carcinoma (UC) whose disease has not progressed after first-line platinum-based chemotherapy. However, evidence on its effectiveness and safety in elderly patients remains limited.MethodsThis multicenter retro-prospective Italian study included 251 patients with advanced UC who received avelumab maintenance between 2021 and 2023. Outcomes were compared between patients aged ≥75 and <75 years. Primary endpoints were progression-free survival (PFS) and overall survival (OS).ResultsAmong 96 elderly and 155 younger patients, median PFS was 7.2 months (95% CI, 4.9–17.5) and 6.7 months (95% CI, 4.9–9.3), respectively (p = 0.547), while median OS was 28.1 months (95% CI, 17.3–42.1) versus 18.5 months (95% CI, 12.0–38.6) (p = 0.238). Immune-related adverse events were infrequent and generally comparable across age groups. In multivariable analyses, lung metastases independently predicted worse OS in elderly patients, whereas bone metastases and concomitant corticosteroid therapy were adverse prognostic factors in younger patients.ConclusionsAvelumab maintenance demonstrated similar efficacy and safety in elderly and younger patients, supporting its use regardless of age. In the evolving therapeutic landscape of advanced UC, this treatment strategy remains a relevant and practical option, particularly for elderly or comorbid patients who may not be candidates for more intensive first-line combinations.

Elderly patients with recurrent ovarian cancer are often underrepresented in clinical trials, complicating treatment decisions because of comorbidities and altered drug tolerance. Trabectedin plus pegylated liposomal doxorubicin is a non-platinum option for patients with a platinum-free interval of 6-12 months. This single-center retrospective study evaluated the efficacy and safety of this combination in 23 patients aged ≥65 years with partially platinum-sensitive relapsed ovarian cancer treated between 2018 and 2022. Median age was 68 years. The median progression-free survival was 6 months (95% CI: 4-9), and the median overall survival was 18 months (95% CI: 12-101). Treatment was generally well tolerated, with mostly grade 1-2 hematologic toxicities, particularly anemia and neutropenia, and no treatment-related deaths. These findings suggest that trabectedin plus pegylated liposomal doxorubicin has clinically meaningful activity and an acceptable safety profile in this elderly population, although confirmation in larger cohorts is needed.

The introduction of immunotherapy, either as monotherapy or in combination with tyrosine kinase inhibitors (TKIs), has profoundly reshaped the first-line treatment of metastatic renal cell carcinoma. Nevertheless, most patients eventually experience disease progression, highlighting the unmet clinical need for effective therapeutic strategies in the post-immunotherapy setting. Cabozantinib, a multikinase TKI targeting VEGFR, MET, and AXL, represents one of the most established treatment options in this context. This mini-review summarizes the biological rationale, key clinical evidence, and the most recent data presented at major international congresses, with a specific focus on the positioning of cabozantinib after failure of immunotherapy-based regimens or immune-TKI combinations.

Ulcerative colitis (UC) is associated with an increased risk of developing colitis-associated colorectal cancer (caCRC), a major complication of long-standing disease. In this review, we examined the pathogenic association between UC and caCRC, highlighting the risk factors, molecular mechanisms, and current strategies for prevention and management. Compared to sporadic colorectal cancer, caCRC tends to occur at a younger age and is more frequently characterized by mucinous or signet-ring cell histology, proximal colonic involvement, and a higher incidence of synchronous lesions. The risk of caCRC increases 8-10 years after UC diagnosis and is influenced by disease duration, extent of colonic involvement, inflammatory burden, family history of colorectal cancer, and coexisting primary sclerosing cholangitis. The inflammation-to-cancer progression follows a multistep pathway of genetic alterations, advancing from low-grade to high-grade dysplasia, and ultimately to carcinoma. While chemopreventive agents such as 5-aminosalicylates may offer some benefit, surveillance colonoscopy remains the primary strategy for risk reduction. Early detection and individualized prevention strategies are critical for improving long-term outcomes in patients with UC.

Recent advancements in cancer multi-omics have transformed our understanding of cancer biology by integrating genomics, transcriptomics, proteomics, and metabolomics. These integrative approaches have led to the identification of novel biomarkers and therapeutic targets, offering deeper insights into the molecular intricacies of various cancers, including breast, lung, gastric, pancreatic, and glioblastoma. Despite these advances, challenges remain, such as the integration of disparate data types and the interpretation of complex biological interactions. However, developments in proteogenomics and mass spectrometry have enhanced the correlation between molecular profiles and clinical features, refining the prediction of therapeutic responses. Future research in cancer drug discovery is poised to benefit from multi-omics approaches, improving the precision and efficacy of personalized therapies. By developing integrative network-based models, researchers aim to address challenges related to heterogeneity, reproducibility, and data interpretation. A standardized framework for multi-omics data integration could revolutionize cancer research, optimizing the identification of novel drug targets and enhancing our understanding of cancer biology. This complete approach holds the promise of advancing personalized therapies by fully characterizing the molecular landscape of cancer, ultimately improving patient outcomes through more effective and targeted treatment strategies. This narrative review underscores the potential of multi-omics approaches to transform cancer research and improve patient outcomes through more precise and effective treatments.

Esophageal cancer is an aggressive malignancy often diagnosed at advanced stages, with esophageal squamous cell carcinoma being the predominant subtype worldwide. Standard first-line chemotherapy provides limited survival benefits, with a median overall survival of less than 1 year. Recent advancements in immunotherapy, particularly immune checkpoint inhibitors (ICIs), have transformed the treatment landscape, improving overall survival and progression-free survival. However, response rates remain variable, with programmed death ligand 1 (PD-L1) expression being the primary predictive biomarker. The variability in PD-L1 testing methods and immune microenvironment alterations after prior treatments complicate patient selection for ICIs. Several phase 3 trials, including KEYNOTE-590 and CheckMate 648, have demonstrated the efficacy of ICIs combined with chemotherapy, particularly in patients positive for PD-L1. Despite these advances, long-term survival remains low, emphasizing the need for better biomarkers and novel therapeutic strategies. This review explored current first-line treatment options for esophageal squamous cell carcinoma, challenges in biomarker-based patient selection, and emerging therapeutic approaches.

CDK4/6 inhibitors have transformed treatment for HR + HER2 − advanced breast cancer (aBC). However, adverse events (AEs) often lead to dose adjustments or discontinuation, potentially impacting outcomes. This study assessed AE incidence and its effect on survival in patients receiving abemaciclib (AB), ribociclib (RB), or palbociclib (PB). A retrospective study of 162 h + HER2 − aBC patients treated with CDK4/6 inhibitors as first-line therapy (July 2017–September 2024) was conducted. AE incidence, progression-free survival (PFS), and overall survival (OS) were analyzed. Most patients (91.4

Breast cancer (BC) is the most commonly occurring type of cancer in women, being a major cancer-related cause of mortality worldwide. With the advancement in current therapeutic options, including hormone therapy and targeted therapies, there is a need for more accurate and less invasive options to monitor cancer progression in patients. Liquid biopsy has evolved rapidly, being able to detect small quantities of nucleic acids or cell-free DNA in the blood of BC patients. This method addresses three major issues of needle biopsy: firstly, it is more permissive by being less invasive and does not require needling the organs; secondly, it covers for the heterogeneous nature of the tumor of origin, which could lead to an otherwise inaccurate representation of the cancer-driving mutations; thirdly, it better represents the type of tumor that the primary tumor is going to evolve into before it starts to metastasize. This current review will address the current advancements in liquid biopsy in the context of BC, highlighting the pros and challenges.

Renal cell carcinoma (RCC) is often diagnosed at a localized stage and treated with surgery. However, up to 40 % of patients may experience recurrence despite complete resection. The introduction of immune checkpoint inhibitors, particularly pembrolizumab, has changed the adjuvant treatment landscape. The Tuscan Interdisciplinary Uro-Oncological Group (GIOTTO) provides practical guidance on patient selection and clinical use of adjuvant pembrolizumab in RCC.

The advent of immunotherapy (IO) has revolutionized the therapeutic landscape of advanced renal cell carcinoma (RCC). The aim of this study is to analyze clinical outcomes in patients who discontinued IO in metastatic RCC first line in a real-world setting. We retrospectively collected data about 1077 patients aged ≥18 years with a histologically confirmed diagnosis of clear cell RCC and histologically or radiologically confirmed metastatic disease, treated in 52 centers from 20 countries, between January 1, 2016 and April 1, 2024, from all three International metastatic renal cell carcinoma (mRCC) Database Consortium risk groups (favorable, intermediate, and poor). Each patient was treated in front-line with IO + Tirosine Kinase Inhibitor or IO + IO combinations. In this study we analyzed survival outcomes comparing patients who interrupted IO versus patients who continuously received it and multivariable analysis. We analyzed the clinical behavior of 185 patients who interrupted IO treatment due to SAE, 127 patients with IO-tyrosine kinase inhibitor, 58 patients with IO-IO versus 892 patients who do not discontinue IO treatment. No significant differences in OS were found in patients who discontinue treatment versus no discontinuation. Moreover, time to discontinuation seemed to be an OS predictor, being inferior in patients who interrupted IO in the first to third month versus patients who discontinued treatment after this time data. The ARON-1 study offers a comprehensive examination of toxicity-related IO discontinuation in advanced RCC, contributing to a better understanding of balancing treatment efficacy with tolerability.