Background: Platinum-based chemotherapy (PBC) followed by avelumab maintenance is a treatment option for patients with advanced urothelial carcinoma (aUC) patients. However, the optimal treatment sequencing in the era of antibody–drug conjugates (ADCs) is yet to be determined. Recent studies suggest that the timing of immune checkpoint inhibitor (ICI) administration may impact patient outcomes, with a potential benefit from morning infusions. Methods: This retrospective study included 105 patients with aUC treated with avelumab in Portugal and intended to assess the safety and clinical outcomes (progression-free survival (PFS), overall survival (OS), and overall response rate (ORR)) and evaluate the impact of treatment timing (morning vs. afternoon) on patient outcomes. Results: The median follow-up from the start of avelumab was 17.7 months, the median PFS (mPFS) was 9.8 months (95% CI 4.9–14.7), and the median OS (mOS) was 39.5 months (95% CI 13.2–65.7). Immune-related adverse events (irAEs) were reported in 65.8% of patients, with 6.7% experiencing G3 irAEs. Among those who received a subsequent-line ADC upon disease progression (43%), the mOS from the start of avelumab was 23.1 months (95% CI 9.2–37.0). Multivariate analysis showed significant improvement in mOS with morning avelumab infusions (HR 0.35, 95% CI: 0.12–0.97, p = 0.042) and a trend towards improved mPFS (HR 0.43, 95% CI: 0.179–1.02, p = 0.055). Conclusions: This study confirms the clinical efficacy and safety of avelumab, showing improved outcomes over JAVELIN Bladder 100 and suggesting that morning infusions may offer a survival benefit in this context. Further research is needed to optimize treatment sequencing and explore the impact of infusion timing in ICI strategies.

Breast cancer has several subtypes, including HER2-positive breast cancer, which is characterized by overexpression of human epidermal growth factor receptor 2 (HER2), aggressiveness, poor prognosis, and high risk of recurrence and metastasis. Brain metastases are a common complication of HER2-positive breast cancer, but brain imaging is not included in the initial staging of this disease. This prospective pilot study aimed to evaluate the usefulness of brain computed tomography (CT) in the initial staging of HER2-positive breast cancer. Fifty-eight patients were enrolled and demographic, clinical, and breast cancer-specific data were collected after the informed consent and ethical approval were obtained. A descriptive analysis was performed. The median age of the patients was 55 years, and the majority had good performance status. Brain CT scans were performed at diagnosis, and no brain metastases were detected in early-stage patients. However, brain CT identified brain metastases in one advanced-stage patient with clinical suspicion. This study suggests that brain CT may have limited utility in the initial staging of early HER2-positive breast cancer, while it could be a valuable tool in advanced cases. Further research is needed, including a higher number of patients to identify those with high risk, which may benefit from brain imaging.

Triple negative breast cancer (TNBC) has been shown to respond to neoadjuvant chemotherapy (NACT). It has been established that achieving pathological complete response (pCR) for certain aggressive subtypes of breast cancer, including HER-2 (over-expressed) and TNBC, provides an important surrogate marker for predicting long-term clinical response and survival outcomes. How to increase the number of patients that achieve pCR remains challenging. Platinum-based NACT seems to be part of the solution and capecitabine, an active drug in metastatic breast cancer, but not a standard one in earlier stages may have found its place in the adjuvant setting. In the near future immunotherapy can play a role in early TNBC

(1) Background: Relapsed HGSOC with ascites and/or pleural effusion is a poor-prognostic population and poorly represented in clinical studies. We questioned if these patients are worth treating. In other words, if these patients received the most effective treatment, would it change the course of this disease? To our knowledge this is the first real-life study to evaluate this question in this low-survival population. (2) Methods: To tackle this question we performed a retrospective, multi-centric, real-life study, that reviewed relapsed HGSOC patients with ascites and/or pleural effusion. Our rationale was to compare the OS of two groups of patients: responders, i.e., patients who had an imagological response to treatment (complete/partial response/stable disease, RECIST criteria) versus non-responders (no response/progression upon treatment). We evaluated the predictive value of clinical variables that are available in a real-life setting (e.g., staging, chemotherapy, surgery, platinum-sensitivity). Multivariate logistic regression and survival analysis was conducted. A two-step cluster analysis SPSS tool was used for subgroup analysis. Platinum sensitivity/resistance was also analyzed, as well as multivariate and cluster analysis. (3) Results: We included 57 patients, 41.4% first line responders and 59.6% non-responders. The median OS of responders was 23 months versus 8 months in non-responders (p < 0.001). This difference was verified in platinum-sensitive (mOS 28 months vs. 8 months, p < 0.001) and platinum-resistant populations (mOS 16 months vs. 7 months, p < 0.001). Thirty-one patients reached the second line, of which only 10.3% responded to treatment. Three patients out of thirty-one who did not respond in the first line of relapse, responded in the second line. In the second line, the mOS for the responders’ group vs. non-responders was 31 months versus 13 months (p = 0.02). The two step cluster analysis tool found two different subgroups with different prognoses based on overall response rate, according to consolidation chemotherapy, neoadjuvant chemotherapy, FIGO staging and surgical treatment. Cluster analysis showed that even patients with standard clinical and treatment variables associated with poor prognosis might achieve treatment response (the opposite being also true). (4) Conclusions: Our data clearly show that relapsed HGSOC patients benefit from treatment. If given an effective treatment upfront, this can lead to a ~3 times increase in mOS for these patients. Moreover, this was irrespective of patient disease and treatment characteristics. Our results highlight the urgent need for a sensitivity test to tailor treatments and improve efficacy rates in a personalized manner.

BACKGROUND: The incidence of central nervous system relapse among patients with breast cancer appears to be increasing, despite advances in systemic treatment. Although achieving pathological complete response (pCR) following neoadjuvant treatment has been associated with improved survival outcomes, it does not seem to prevent brain relapse. In early stage HER 2 positive disease between 10-14% will develop brain metastases and the risk is higher in endocrine receptor-negative setting. Identifying patients who are at greater risk of brain relapse can help to indicate those who need new treatment options to prevent it. This study aimed to assess the incidence of brain relapse in a multicenter cohort of patients who underwent neoadjuvant treatment across nine hospitals located in Portugal, Spain, and Chile, and to identify factors associated with it. MATERIAL AND METHODS: We conducted a retrospective analysis of patients diagnosed and treated for HER2-positive breast cancer in nine hospitals located in Portugal, Spain, and Chile between January 2017 and December 2022. To be eligible for inclusion, patients must have undergone neoadjuvant anti-HER2 therapy followed by surgery. Data such as age at diagnosis, endocrine receptor expression, chemotherapy regimen, pathological response, adjuvant anti-HER2 treatment, endocrine therapy, and first local of relapse were analysed. RESULTS: A total of 396 patients with a mean age of 52.9 years were included in the study. All patients received a neoadjuvant chemotherapy regimen and double anti-HER2 therapy with trastuzumab and pertuzumab, with a pathological complete response (pCR) achieved in 59.6% of patients. Nearly all patients (98.2%) received adjuvant anti-HER2 therapy, with 83.81% receiving trastuzumab, 12.85% receiving TDM1, and 3.34% receiving trastuzumab plus pertuzumab. Over a follow-up period of 3.5 years, 23 patients (5.81%) experienced relapse. Among these cases, 10 patients (2.5%) had brain relapse as first site, accounting for 43.48% of the total recurrences. Brain relapse was not associated with pathological response, but rather with a more advanced stage at diagnosis (T3/4 or Nodal positive) (p<0.05). CONCLUSION: In CONCLUSION: , our multicentric cohort study provides valuable insights into the incidence and factors associated with brain metastasis in HER2-positive breast cancer patients who underwent neoadjuvant treatment. Our findings suggest that although neoadjuvant treatment resulted in a high rate of pCR, it did not prevent brain relapse. Importantly, our study identified advanced disease stage at diagnosis as a significant risk factor for brain relapse. Further studies are needed to identify additional factors associated with brain metastasis and explore potential preventive strategies in patients with higher risk.