Background: Approximately 25–30% of non-small-cell lung cancer (NSCLC) patients are diagnosed when the disease is still resectable, although the risk of recurrence is significant. Recently, approaches based on targeted agents or immune checkpoint inhibitors (ICIs) have modified the management of such patients. However, some questions remain unanswered. Objectives: Our aim is to assess the current evidence on approaches involving targeted agents and ICIs in resectable NSCLC, to provide an up-to-date overview of the subject, and to identify areas of current debate, Methods: We analyzed randomized trials on ICIs and targeted therapies in early-stage NSCLC, published or presented at international oncology meetings throughout the last 5 years. Results: Osimertinib and alectinib have shown robust results in the adjuvant setting for molecularly identified patient subgroups, while ICIs have achieved robust data in the neoadjuvant/perioperative setting, with less consistent data on the pure adjuvant approach. Circulating tumor DNA levels may offer a possible biomarker for therapeutic decisions, albeit more prospective data are needed. Conclusions: Targeted agents and ICIs are revolutionizing early-stage NSCLC, similarly to what was observed in advanced disease. Prospective studies designed to compare neoadjuvant, adjuvant, and perioperative approaches and to assess the role of circulating biomarkers are warranted.

BACKGROUND:Antibody-drug conjugates are novel effective therapies for metastatic breast cancer. Nevertheless, their toxicity profile can significantly affect patients' quality of life over time. METHODS:This is a systematic review and meta-analysis of randomized controlled trials of antibody-drug conjugates currently approved for the treatment of metastatic breast cancer [trastuzumab-emtansine (T-DM1), trastuzumab deruxtecan (T-DXd) and sacituzumab-govitecan (SG)] versus standard therapy to evaluate the risk of adverse events, discontinuation rate due to toxicity, impact on quality of life according to EORTC QLQ-C30 scale and subdomains. Relative risks (RR) and hazard ratios (HR) with 95% CIs were calculated using random effects models. RESULTS:Nine trials with a total of 5753 patients were included. The most common adverse events of any grade for T-DM1 included thrombocytopenia (RR 7.14, 95% CI 4.13-12.36) and increased alanine-transaminase (ALT) (RR 2.04, 95% CI 1.43-2.91), for T-DXd were nausea (RR 2.39, 95% CI 1.90-3.00) and anemia (RR 1.55, 95% CI 1.27-1.90), while for SG were neutropenia (RR 1.30, 95% CI 1.14-1.49), diarrhea (RR 3.62, 95% CI 2.97-4.42) and nausea (RR1.90, 95% CI 1.65-2.19). Severe adverse events such as interstitial lung disease and left ventricular dysfunction were peculiar of T-DXd. Antibody-drug conjugates significantly delayed clinical deterioration of global health status by EORTC QLQ-C30 (HR .71, 95% CI .59-.86), physical, emotional and social functioning, pain and fatigue symptoms. CONCLUSIONS:This meta-analysis offers consolidated data on adverse events associated with antibody-drug conjugates and their effects on patients' quality of life, emphasizing differences based on the specific agent. These findings underscore the critical need for effective strategies to prevent, diagnose and manage these toxicities.

Background Universal screening of colorectal cancer (CRC) patients for Lynch syndrome (LS) through MisMatch Repair (MMR) testing is recommended. BRAFV600E mutation and/or MLH1 promoter methylation (Reflex Testing, RefT)generally rule out LS in MLH1-deficient (dMLH1) patients. We estimated the impact of RefTon genetic counseling (GC) and on the diagnostic yield of genetic testing (GT). Methods Overall, 3199 CRC patients were referred to our center between 2011 and 2021. Patients referred until January 2019 (n=2536) underwent universal MMR testing and were termed ‘Cohort A’; among patients after February 2019 (n=663), ‘Cohort B’, RefT was also performed in dMLH1 patients. Results Overall, 401/3199 patients (12.5%) were MMR-deficient (dMMR); 312 (77.8%) in cohort A and 89 (22.2%) inB; 346/401 were dMLH1 (86.3%), 262/312 (83.9%) in cohort A and 84/89 (94.3%) in B. In Cohort A, 91/312 (29.1%) dMMR patients were referred to GC, 69/91 (75.8%) were in the dMLH1 group; 57/69 (82.6%) dMLH1 patients underwent GT and 1/57 (1.7%) had LS. In Cohort B, 3/84 dMLH1 patients did not undergo BRAF testing. Three BRAF wt and not hypermethylated of the remaining 81 dMLH1 patients were referred to GC and GT, and one had LS. This diagnostic pathway reduced GC referrals by 96% (78/81) in Cohort B and increased the diagnostic yield of GT by about 20 times. Conclusion Our findings support RefT in dMLH1 CRC patients within the LS diagnostic pathway, as it reduces the number of GC sessions needed and increases the diagnostic yield of GT.

Vitamin D is rightly recognized as an essential key factor in the regulation of calcium and phosphate homeostasis, affecting primary adequate bone mineralization. In the last decades, a more complex and wider role of vitamin D has been postulated and demonstrated. Cardiovascular diseases have been found to be strongly related to vitamin D levels, especially to its deficiency. Pre-clinical studies have suggested a direct role of vitamin D in the regulation of several pathophysiological pathways, such as endothelial dysfunction and platelet aggregation; moreover, observational data have confirmed the relationship with different conditions, including coronary artery disease, heart failure, and hypertension. Despite the significant evidence available so far, most clinical trials have failed to prove any positive impact of vitamin D supplements on cardiovascular outcomes. This discrepancy indicates the need for further information and knowledge about vitamin D metabolism and its effect on the cardiovascular system, in order to identify those patients who would benefit from vitamin D supplementation.

Breast cancer is the most common cancer in women, and luminal breast cancer is the predominant subtype, characterized by the presence of estrogen receptors and/or progesterone receptors in tumor cells. Adjuvant endocrine therapy is the pivotal approach in the management of luminal early breast cancer. Hence, new therapeutic approaches have been studied during the last few years, especially in patients with high risk of recurrence.Here we provide a summary of the most recent clinical trials evaluating adjuvant treatment in hormone-receptors-positive early breast cancer. First, the main cornerstone is related to the role of extended endocrine treatment, which has been widely investigated to access a benefit in disease-free survival and overall survival (only the GIM4 trial has positive feedback about survival) and to tailor the treatment according to patient compliance. The results highlighted an advantage in extending the use of endocrine treatment for at least seven full years, considering aromatase inhibitors as principal drugs. Second, the shift of CDK4/6 inhibitors (CDK4/6i) from advanced to early setting reported positive outcomes, with favorable results from MonarchE and NATALEE trials, using Abemaciclib and Ribociclib respectively, even if non-negligible toxicities have been reported. Last, the use of PARP inhibitors for BRCA1/2 mutated patients has been evaluated in the OlympiA trial (Olaparib), observing a comparable benefit between hormone-receptors-positive and triple-negative early breast cancer.However, more data are still required to better select patients that could benefit more from CDK4/6i considering side effects too, and sequential treatments are still not codified.

Abstract Background: The long-term results of the Italian randomized phase III GIM2 study showed that, in women with node-positive breast cancer (BC), dose-dense (DD) chemotherapy significantly improved both disease-free survival (DFS) and overall survival (OS) compared with standard-interval (SI) chemotherapy. Obesity has been identified as an independent poor prognostic factor in patients with BC, with a potential negative impact on the efficacy and toxicity of systemic therapies. Nevertheless, the specific influence of body mass index (BMI) on the efficacy of different adjuvant chemotherapy schedules (DD or SI) remains a subject of debate. This analysis aimed to investigate this hypothesis in patients enrolled in the GIM2 trial. Methods: GIM2 was a randomized multicentric phase III trial that compared different chemotherapy schedule (DD vs SI) and regimen (FEC-P vs EC-P) in 2091 node-positive early breast cancer patients. BMI (kg/m2) was categorized as follows: < 18.5 (underweight), 18.5 to < 25 (lean), 25 to < 30 (overweight), and ≥ 30 (obese). The primary endpoint was to assess association between BMI and DFS and OS. Survival estimates were compared using the Kaplan-Meier method and log-rank test. Univariate and multivariable Cox proportional hazard models, adjusted for relevant prognostic factors, were used. Results: A total of 1925 patients were included in the present analysis, of whom 31.6% (n=632) were overweight and 19.3% (n=386) obese. Median age was 52 years. Overweight-obesity condition was significantly associated with postmenopausal status, greater representation of T2-T4 tumors with N > 2 in both patients in the DD and SI arm. After a median follow-up of 15.0 years (IQR 8.4-16.3), compared to patients with normal BMI, those who were overweight or obese at diagnosis had a higher risk of experiencing a DFS event (Hazard Ratio [HR] 1.11 95% CI 0.94-1.31 and HR 1.37 95%CI 1.14-1.65, respectively, p=0.003) and OS event (HR 1.11 95% CI 0.89-1.38 and HR 1.59 95%CI 1.26-2.01, respectively, p=0.0003). No significant interaction was found between BMI and treatment schedule in terms of DFS (p for interaction=0.56) nor OS (p for interaction=0.19). At the multivariate analysis, in the DD arm, adjusted HR (aHR) for DFS and for OS were 1.01 (95% CI 0.75- 1.35) and 1.04 (95% CI 0.72-1.52) for obese vs. normal BMI groups, and 0.88 (95% CI 0.68- 1.15) and 0.77 (95%CI 0.54-1.10) for overweight vs. normal BMI groups, respectively. In the SI arm, aHRs for DFS and OS were 1.24 (95% CI 0.94- 1.63) and 1.35 (95%CI 0.96- 1.90) for obese vs. normal BMI groups, and 1.04 (95%CI 0.82- 1.33) and 1.01 (95% CI 0.74-1.40) for overweight vs. normal BMI groups, respectively. Similar results were observed when considering hormone receptor-positive and negative BC separately. Conclusion: In the GIM2 trial, BMI was prognostic but not predictive of different benefit to adjuvant chemotherapy. In high-risk patients, DD schedule should be considered the preferred schedule irrespective of BMI. Citation Format: Francesca Poggio, Eva Blondeaux, Marco Tagliamento, Marta Perachino, Simone Nardin, Benedetta Conte, Sabino De Placido, Mario Giuliano, Valeria Forestieri, Michelino De Laurentiis, Adriano Gravina, Giancarlo Bisagni, Anita Rimanti, Anna Turletti, Cecilia Nisticò, Angela Vaccaro, Francesco Cognetti, Alessandra Fabi, Simona Gasparro, Ornella Garrone, Ylenia Urracci, Maria Grazia Alicicco, Mauro Mansutti, Paola Poletti, Pierpaolo Correale, Claudia Bighin, Fabio Puglisi, Filippo Montemurro, Giuseppe Colantuoni, Luca Boni, Matteo Lambertini, Lucia Del Mastro. Impact of Body Mass Index (BMI) on the efficacy of different adjuvant chemotherapy schedules in patients with breast cancer: analysis from the randomized phase III GIM2 trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-03-02.

INTRODUCTION:We conducted an online survey to investigate oncologists' clinical practices and views on palliative care at the end of life in the Italian region of Liguria. METHODS:The survey included 29 items divided into three sections: participant characteristics (n=6), hospital resources and practices (n=11), participant practices and views (n=12). RESULTS:Twenty-one of the 41 medical oncologists invited completed the survey (51%). Although almost all reported the presence of palliative medicine physicians at their hospitals (90%), nearly half (48%) stated that palliative medicine physicians were not responsible for managing cancer patients at end of life, and 21% reported routine participation of palliative medicine physicians in multidisciplinary meetings. Thirty-eight percent of the respondents stated they never consulted psychologists regarding end of life patient care, and 43% reported they rarely did. Notably, a substantial proportion of participants stated that they administered active treatments to patients with six months life expectancy. Regarding integration between oncology and palliative medicine, an equal proportion felt it had been fully (48%) or partially achieved (48%) at their hospitals. CONCLUSIONS:Participants seemed fairly satisfied with the level of integration between oncology and palliative medicine at their hospitals, which contrasts with other findings regarding, for instance, the scant participation of palliative medicine physicians in multidisciplinary meetings. Exploring the impact of the novel regional clinical healthcare pathway for palliative care on practices at hospitals in Liguria will be crucial to ensure that cancer patients at end of life receive quality care.

Background The phase III GIM2 trial showed improved disease-free survival (DFS) and overall survival (OS) with adjuvant dose-dense (DD) as compared with standard-interval (SI) chemotherapy in women with node-positive early-stage breast cancer (BC). This exploratory analysis aimed to investigate the benefit of different schedules according to body mass index (BMI) in this trial. Patients and methods This analysis explored the efficacy, in terms of DFS and OS, of different chemotherapy schedules according to BMI. Univariate and multivariable Cox proportional hazard models, adjusted for relevant prognostic factors, were used. Results Out of 2091 patients enrolled, 1925 with known baseline BMI were randomized in the DD versus SI comparison and therefore included in this analysis: 31.6% were overweight and 19.3% obese. Overweight and obesity were significantly associated with postmenopausal status, pT >2, and pN >2 tumors. After a median follow-up of 15.0 years (interquartile range 8.4-16.3 years), multivariable Cox survival models demonstrated no association of different BMI categories on DFS [adjusted hazard ratio (adjHR) 0.96, 95% confidence interval (CI) 0.80-1.15 and adjHR 1.11, 95% CI 0.91-1.35 for overweight and obese patients, respectively, compared to patients with normal BMI] or OS (adjHR 0.90, 95% CI 0.71-1.14 and adjHR 1.18, 95% CI 0.92-1.52 for overweight and obese patients, respectively). No significant interaction was found between BMI and treatment schedule in terms of DFS (Pfor interaction = 0.56) or OS (Pfor interaction = 0.19). The survival benefit of DD chemotherapy was observed irrespective of different BMI categories, with a more pronounced benefit for overweight and obese patients. Conclusion In node-positive BC patients, DD schedule should be considered the preferred schedule irrespective of BMI.

Adjuvant endocrine therapy (ET) with exemestane combined with LHRH analog (LHRHa) is standard of care for premenopausal women with hormone receptor-positive breast cancer. However, LHRHa may not always achieve complete ovarian suppression in these patients. The PREFER-Fertility (NCT02895165) and GIM 23-POSTER (NCT05730647) are prospective, observational studies that enrolled premenopausal women eligible to receive (neo)adjuvant chemotherapy and/or ET. We conducted an exploratory analysis of patients achieving suboptimal suppression of ovarian function enrolled at the coordinating center of both studies, defined as estradiol levels greater than 25.1 ng/L or resumption of menstruation at least 3 months after the start of exemestate plus LHRHa. As of February 2024, a total of 1616 patients were enrolled (766 in the PREFER and 850 in the GIM 23), of whom 528 patients included from the main center. Among them, 26 (4.9%) had a suboptimal ovarian suppression. Median age of these patients was 39 (interquartile range (IQR) 36-46). Median body mass index was 21.8 kg/m2 (84.6% <25). Main histopathological characteristics are summarised in the table. 65.4% of these patients received chemotherapy, mainly anthracycline plus taxane (93.8%), and 3 patients received adjuvant abemaciclib. Median time from last chemotherapy to suboptimal ovarian suppression was 7 months, with 17 patients already on LHRHa during chemotherapy. Monthly leuprorelin was given in 65% of the cases, while the others received monthly triptorelin. Median time to suboptimal ovarian suppression was 7 months (IQR: 5-20). At median follow-up of 5 years (IQR: 2-6), 3 patients had a relapse of disease.Table: 125PCharacteristicsN of patients (%)TNM - StageIA14 (53.9)IB3 (11.5)IIA5 (19.2)IIB2 (7.7)IIIA2 (7.7)Grading11 (3.8)218 (69.3)35 (19.2)NA2 (7.7)HistologyDuctal21 (80.8)Lobular1 (3.8)Other4 (15.4)Ki67<2012 (46.2)≥2014 (53.8)HER2 status012 (46.1)1+5 (19.2)2+2 (7.7)2+ FISH amplified or 3+7 (27) Open table in a new tab In our cohort, almost 5% of premenopausal patients did not achieve ovarian suppression with LHRHa. Oncologists should be aware that serial monitoring of estradiol levels should be performed to address this.

1024 Background: Estrogen receptors (ER) are considered predictive biomarkers to identify ER+ MBC patients who would likely benefit from endocrine therapies (ET). However, 30 to 40% of ER+ MBC patients fail to achieve a durable response. 18F-FES PET/CT has been shown to represent a valuable and accurate diagnostic tool to determine ER status at the level of metastatic sites and can be proposed as a valid alternative to biopsy of metastatic lesions. In this trial, we evaluated 18F-FES PET/CT as a predictive tool for endocrine responsiveness in ER+ MBC. Methods: ET-FES is an international, multicenter, academic clinical trial, conducted within the JTC-2011 ERA-NET TRANSCAN programme. Patients with ER+/HER2- MBC and first evidence of relapse were eligible for the study. All patients underwent a baseline 18F-FES PET/CT in addition to conventional staging procedures. Tumors were classified as endocrine sensitive if overall Standardized Uptake Value (SUV) ≥ 2; SUVmax was measured in the 3 largest lesions to quantify ER expression and a cutoff value of 2 was used to dichotomize results (endocrine sensitive vs resistant). In the ET-FES trial, patients with SUV ≥ 2 received single agent ET until PD; patients with SUV < 2 were randomized to receive single agent ET or chemotherapy (CT). The predictive role of 18F-FES PET/CT results was assessed for PFS and OS by univariate and multivariate analyses. Results: Overall, 147 patients (142 for ITT analysis) were enrolled from 04/2015 to 12/2020; 113 presented with 18F-FES SUV ≥ 2 and received ET; 29 pts, with SUV < 2 were randomly assigned to ET or first line chemotherapy (CT), following local clinical practice. After a median follow up of 4.6 years, 51 deaths had occurred (54.2%). Median PFS was 18,0 months (95%CI 11,2- 22,9) in the overall population and in 18F-FES SUV ≥ 2 versus 12,4 months (95%CI 3,1 – NR) in patients with SUV <2 treated with ET and 23.0 months (95%CI 7,7 – 30,0) if treated with CT. Median OS was not reached in the overall patient population and in patients with SUV ≥2, treated with single agent ET. Median OS was 28.1 months (95%CI 14,2 – NR) in patients with SUV <2 treated with ET versus 52,8 months (95%CI 16,1 – NR) if treated with CT. The Kaplan–Meier estimate of OS at 48 months was 64.4% (SE +/-5%) in all patients and 66% in 18F-FES SUV ≥ 2; at 60 months was 54.4% (SE +/-6%) and 57% (SE +/-5%), respectively. Among the 113 pts with SUV ≥ 2 treated with ET, the Kaplan–Meier estimate of OS at 60 months was 73.0% if treated with aromatase inhibitors versus 35% in case of fulvestrant or tamoxifen (p< 0.0005). Conclusions: ET-FES is the first prospective trial to assess the efficacy of ET alone in patients selected for endocrine responsiveness on the basis of whole body molecular ER imaging by 18F-FES PET/CT. These results suggest that the efficacy of ET may be maximized by using the appropriate assessment of endocrine responsiveness at the different metastatic sites. Clinical trial information: EUDRACT 2013-000-287-29 .

Transgender and gender-diverse (TGD) individuals face an elevated risk of cancer in comparison with the general population. This increased risk is primarily attributed to an imbalanced exposure to modifiable risk factors and a limited adherence to cancer screening programmes, stemming from historical social and economic marginalisation. Consequently, these factors contribute to poorer clinical outcomes in terms of cancer diagnosis and mortality. A focal point of interest is the potential carcinogenic effect of gender-affirming hormone therapy (GAHT). It is crucial to recognise that GAHT serves as an essential, life-saving treatment for TGD individuals. Therefore, if a demonstrated direct correlation between GAHT and elevated cancer risk emerges, essential shared decision-making discussions should occur between oncology practitioners and patients. This narrative review aims to collect and discuss evidence regarding potential correlations between GAHT and the most prevalent tumours known to be influenced by sex hormones. The objective is to comprehend how these potential carcinogenic effects impact health and inform health interventions for TGD individuals. Unfortunately, the scarcity of epidemiological data on cancer incidence in the TGD population persists due to the absence of sexual orientation and gender identity data collection in cancer centres. Consequently, in most cases, establishing a positive or negative correlation between GAHT and cancer risk remains speculative. There is an urgent need for concerted efforts from researchers and clinicians worldwide to overcome barriers and enhance cancer prevention and care in this specific population.

IntroductionThe treatment landscape of non-small cell lung cancer (NSCLC) has seen significant advancements in recent years, marked by a shift toward target agents and immune checkpoint inhibitors (ICIs). However, chemotherapy remains a cornerstone of treatment, alone or in combination. Microtubule-targeting agents, such as taxanes and vinca alkaloids, play a crucial role in clinical practice in both early and advanced settings in NSCLC.Area coveredThis review outlines the mechanisms of action, present significance, and prospective advancements of microtubule-targeting agents (MTAs), with a special highlight on new combinations in phase 3 trials. The online databases PubMed, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched using the terms 'Microtubule-targeting agents' and 'non-small cell lung cancer' or synonyms, with a special focus over the last 5 years of publications.Expert opinionDespite the emergence of immunotherapy, MTA remains crucial, often used alongside or after immunotherapy, especially in squamous cell lung cancer. Next-generation sequencing expands treatment options, but reliable biomarkers for immunotherapy are lacking. While antibody-drug conjugates (ADCs) show promise, managing toxicities remain vital. In the early stages, MTAs, possibly with ICIs, are standard, while ADCs may replace traditional chemotherapy in the advanced stages. Nevertheless, MTAs remain essential in subsequent lines or for patients with contraindications.

OBJECTIVES:To better understand the type of care offered to Italian patients with advanced breast cancer at the End-of-Life (EoL), we conducted a retrospective observational study. EoL was defined as the period of six months before death.METHODS:One hundred and twenty-one patients with advanced breast cancer (ABC) treated at IRCCS San Martino Policlinic Hospital who died between 2017 and 2021 were included. Data about patient, disease, and treatment characteristics from breast cancer diagnosis to death, along with information about comorbidities, medications, imaging, specialist evaluations, hospitalization, palliative care and home care, hospice admissions, and site of death were collected.RESULTS:98.3% of the patients received at least one line of active treatment at EoL; 52.8% were hospitalized during the selected period. Palliative (13.9%), psychological (7.4%), and nutritional evaluations (8.2%) were underutilized. Palliative home care was provided to 52% of the patients. Most of the patients died at home (66.1%) and fewer than one out of five (18.2%) died at the hospital. Among the patients who died at home, 27.3% had no palliative support.CONCLUSIONS:Our findings indicate that palliative care in EoL breast cancer patients is still inadequate. Only a minority of patients had psychological and nutritional support While low nutritional support may be explained by the fact that typical symptoms of ABC do not involve the gastrointestinal tract, the lack of psychological support suggests that significant barriers still exist. Data on the site of death are encouraging, indicating that EoL management is increasingly home centered in Italy.

Background: Lung cancer patients diagnosed following emergency admission often present with advanced disease and poor performance status, leading to suboptimal treatment options and outcomes. This study aimed to investigate the clinical and molecular characteristics, treatment initiation, and survival outcomes of these patients. Methods: We retrospectively analyzed data from 124 patients diagnosed with lung cancer following emergency admission at a single institution. Clinical characteristics, results of molecular analyses for therapeutic purpose, systemic treatment initiation, and survival outcomes were assessed. Correlations between patients’ characteristics and treatment initiation were analyzed. Results: Median age at admission was 73 years, and 79.0 % had at least one comorbidity. Most patients (87.1 %) were admitted due to cancer-related symptoms. Molecular analyses were performed in 89.5 % of advanced non-small cell lung cancer (NSCLC) cases. In this subgroup, two-thirds (66.2 %) received first-line therapy. Median overall survival (OS) was 3.9 months for the entire cohort, and 2.9 months for patients with metastatic lung cancer. Among patients with advanced NSCLC, OS was significantly longer for those with actionable oncogenic drivers and those who received first-line therapy. Improvement of performance status during hospitalization resulted in increased probability of receiving first-line systemic therapy. Discussion: Patients diagnosed with lung cancer following emergency admission demonstrated poor survival outcomes. Treatment initiation, particularly for patients with actionable oncogenic drivers, was associated with longer OS. These findings highlight the need for proactive medical approaches, including improving access to molecular diagnostics and targeted treatments, to optimize outcomes in this patient population.

One third of ABC pts is currently represented by women aged over 70. However, this population remains under-represented in clinical trials. Recently, T-DXd revolutionized the treatment of HER2 positive ABC, demonstrating its efficacy in DESTINY-Breast trials. Its safety profile was manageable and most adverse events (AEs) were gastrointestinal in nature. Nevertheless, T-DXd was associated with the development of interstitial lung disease (ILD) in 10-15% of pts. Thus, some concerns could raise regarding those outcomes in elderly patients. The aim of this retrospective analysis was to evaluate the safety and efficacy of T-DXd in ABC pts over 70 in a real-life setting. TREX-Old is an European retrospective registry evaluating the real-life use of T-DXd in ABC pts aged ≥ 70 among 4 centers across Austria, France, Italy and Portugal. Clinical and pathological characteristics, previous treatments and AEs were collected. Overall, to date, 27 pts were enrolled. Median age was 74 years (range 70-81), with 10 patients over 75 (37%). The ECOG performance status was 0, 1 and ≥ 2 in 22%, 56% and 22% of pts, respectively. Among them, 37% had cardiovascular comorbidities. The median number of lines before T-DXd was 3 (1-13). At treatment initiation, 71% and 29% of pts had a visceral and non-visceral (bone only, skin or lymph nodes) disease, respectively. Eight pts (30%) started with a dose-reduction, and 8 pts (30%) had secondary dose adjustment. Overall, any-grade treatment-related AEs occurred in 19 pts (70%). Among them, nausea was the most common AE (37%), followed by asthenia (18%). Three out 27 pts (11%) developed ILD. Finally, at a median follow-up of 9.5 months (1-29), median PFS was 12 months, considering that only 8 pts progressed at time of current analysis. With the limit of number and follow-up, our data suggest that T-DXd is not associated with new safety signals in pts ≥ 70 years. ILD occurrence was in line with previously reported data. Therefore, age should not be a criterion to discourage treatment with T-DXd. This registry is ongoing, and updated data will be presented.

Coronary artery disease (CAD) is the leading cause of death worldwide. It is a result of the buildup of atherosclerosis within the coronary arteries. The role of the immune system in CAD is complex and multifaceted. The immune system responds to damage or injury to the arterial walls by initiating an inflammatory response. However, this inflammatory response can become chronic and lead to plaque formation. Neutrophiles, macrophages, B lymphocytes, T lymphocytes, and NKT cells play a key role in immunity response, both with proatherogenic and antiatherogenic signaling pathways. Recent findings provide new roles and activities referring to endothelial cells and vascular smooth muscle cells, which help to clarify the intricate signaling crosstalk between the involved actors. Research is ongoing to explore immunomodulatory therapies that target the immune system to reduce inflammation and its contribution to atherosclerosis. This review aims to summarize the pathogenic interplay between immunity and CAD and the potential therapeutic strategies, and explore immunomodulatory therapies that target the immune system to reduce inflammation and its contribution to atherosclerosis.