Background: Ribociclib, palbociclib and abemaciclib are currently approved CDK4/6 inhibitors along with aromatase inhibitors as the first-line standard-of-care for patients with hormone receptor-po...

Histamine and H1 receptors play a crucial role in the tumor microenvironment. Preclinical data showed that concomitant use of antihistamines and immune checkpoint inhibitors (ICIs) might increase the effect of ICIs. This study aimed to evaluate the impact of antihistamines on the oncological outcomes of ICIs. This retrospective study was conducted in a tertiary cancer center. Advanced cancer patients treated with ICIs were included in this study. A total of 133 patients receiving ICIs in the metastatic setting were included. Melanoma (33.1%) was the most common tumor type. The most common ICI was nivolumab (63.2%). Fifty-five (38.4%) patients received antihistamines concomitantly with ICIs. The most common antihistamine was pheniramine (85.5%). The median progression-free survival (PFS) (8.2 vs. 5.1 months, P = 0.016) and overall survival (OS) (16.2 vs. 7.7 months, P = 0.002) were longer in patients receiving antihistamines concomitantly with ICIs. In multivariate analysis, PFS [hazard ratio (HR) = 0.63, 95% CI: 0.40–0.98, P = 0.042] and OS (HR = 0.49, 95% CI: 0.29–0.81, P = 0.006) were also better in those patients after adjusting for confounding factors, such as performance status, bone or liver metastasis, and concurrent chemotherapy. This study suggested that antihistamines may enhance the efficacy of ICIs in patients with advanced cancer. If validated in prospective trials, antihistamines and ICIs combinations might be new options to improve oncological outcomes.

Purpose: Immunotherapy efficacy in elderly patients with comorbidities and poor performance status is not well understood. More knowledge on this topic is needed to identify subgroups that will benefit from immunotherapy. We aimed to evaluate the effect of comorbidity burden in patients receiving immunotherapy. Methods/patients: Patients older than 18 years of age and diagnosed with various malignancies, followed up in our tertiary cancer center were screened. Patients treated with immunotherapy were included in this study. We used to Charlson Comorbidity Index (CCI) to evaluate patients’ comorbidity burden. The primary outcome was overall survival (OS). Hazard ratio (HR) with confidence interval (CI) was evaluated in multivariable analysis. Results: A total number of 197 patients were included. The median age was 62 years. Patients were grouped based on CCI scores: CCI-low (≤ 8) and CCI-high (> 8). One-hundred and seven patients (54.9%) had metastatic disease at the time of diagnosis. Most frequently used immunotherapy agent was nivolumab (n = 124, 62.9%), followed by pembrolizumab (n = 36, 18.3%). The median OS was shorter in the CCI-high group than in the CCI-low group (10.6 vs. 21.2 months, p = 0.002) In multivariable analysis, treatment with anti-CTLA4 (HR: 1.85, 95% CI 1.07–3.20, p = 0.028), ECOG performance status (2–4 vs. 0–1) (HR: 2.17; 95% CI 1.25–3.75; p = 0.005), and higher CCI scores (CCI-high vs. CCI-low) (HR: 1.97; 95% CI 1.3–3.0; p = 0.001) were independently associated with worse OS. Conclusions: Comorbidity burden and performance status independently predict survival outcomes in immunotherapy-treated cancer patients. Comprehensive comorbidity assessment is essential for optimizing treatment and improving patient outcomes.

Background: Low serum sodium affects cancer prognosis, but its impact on immunotherapy is unclear. Objective: Assessing the association of pre- and post-ICI treatment sodium levels with survival. Methods: We retrospectively analyzed patients receiving ICI in January 2012-December 2023, collecting serum sodium levels at treatment initiation and 4 weeks post-ICI, with overall survival (OS) as the primary outcome. Results: Low sodium was observed in 125 and 119 patients pre-and post-treatment respectively. Pre-ICI and post-ICI low sodium correlated with decreased OS [10.6 vs. 22.9 months (p = 0.001) and 11.6 vs. 27.2 months (p = 0.009)]. Multivariate analysis identified pre-ICI low sodium [HR: 1.685; 95% CI: 1.050-2.705; p = 0.031] as an independent risk factor for worse OS. Conclusion: Low baseline serum sodium was an independent risk factor for poor OS in patients treated with ICIs.

(1) Background: Metastatic L-type sarcomas (liposarcoma and leiomyosarcoma) are rare and have a poor prognosis. Trabectedin is an effective agent that can be used after anthracyclines. This study was designed to evaluate the real-life effectiveness and safety of trabectedin. (2) Methods: A retrospective multicenter study was conducted on patients who were treated with trabectedin for metastatic L-type sarcomas at ten tertiary oncology centers between 2015 and 2023. The objective response rate (ORR), disease control rate (DCR), time to treatment failure (TTF), and overall survival (OS) were evaluated in the cohort. Cox regression analysis was used to determine prognostic factors for survival. (3) Results: A total of 98 patients (52% liposarcoma and 48% leiomyosarcoma) were included in the study. The median treatment line was three (range: 1 to 6). Thirteen patients (13.3%) underwent local treatment due to oligoprogression, and dose reduction was required in seventeen patients (17.3%) due to toxicity. The ORR and DCR were 16% and 42%, respectively. The median TTF was 3 months, and the median OS was 10 months. In univariate analysis, a significantly longer median TTF was observed in patients who underwent local treatment (p = 0.008), obtained objective responses (p < 0.001), and underwent dose reduction (p = 0.002). No statistical differences were observed according to the histologic subtype and metastatic site. In the multivariate analysis for OS, it was found that obtaining an objective response was a good prognostic factor (p = 0.003), while the presence of liver metastases was associated with a poor prognosis (p = 0.016). (4) Conclusion: Trabectedin is a suitable option for L-type sarcoma after doxorubicin-based treatments. Survival was not worse in patients who underwent dose reduction. The use of local therapies simultaneously with trabectedin can be effective.

Aim: Hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative breast cancer which represents the most common subgroup of metastatic breast cancer (MBC). Recently, further subclassification for HER2-negative tumors has emerged as HER2-low. There is limited knowledge regarding the effect of HER2-low expression on outcomes of patients with HR-positive and HER2-negative MBC treated with CDK 4/6 inhibitors plus hormonal therapy. Therefore, we evaluated survival parameters according to HER2-low status for this patient group in this study. Material and Methods: As the Turkish Oncology Group (TOG) Project, retrospectively collected data from 423 patients with HR-positive/HER2-negative MBC treated with ribociclib and palbociclib plus letrozole therapy was assessed. Included patients had metastatic first-line therapy and endocrine-sensitive disease. Survival outcomes were compared between HER2-negative and HER2-low patient groups. Conclusion: HER2-low status had no statistically significant impact on survival in patients treated with palbociclib or ribociclib plus letrozole.