Management of Trastuzumab Deruxtecan-related nausea and vomiting in real-world practice.

Background: Nausea and vomiting are common side effects of Trastuzumab Deruxtecan (T-DXd), but guidelines for optimal management were not initially available. This retrospective single-center study aimed at evaluating the efficacy of two antiemetic regimens in patients receiving T-DXd. Methods: Data from metastatic breast cancer patients receiving T-DXd were collected. Two groups were defined: patients treated with 5-HT3 receptor antagonists (RA) ± dexamethasone (5-HT3-group) and patients treated with a fixed oral combination of netupitant (NK1RA) and palonosetron ± dexamethasone (NK1 group). Physicians preferentially offered the NK1 regimen to patients at higher risk of nausea and vomiting based on internal recommendations. Only nausea and vomiting during cycles 1 and 2 were considered. Comparisons of nausea and vomiting by the antiemetic prophylaxis group were assessed using chi-square. Results: A total of 53 patients were included in the analysis. At cycle 1, 72% and 28% of patients received the 5-HT3 and NK1 prophylaxis, respectively. Overall, 58% reported nausea, with no differences between groups (58% vs. 60%; p = 0.832), but with a trend for lower grade in the NK1 group (33.3% G1; 26.7% G2) compared to the 5-HT3 group (23.7% G1; 31.6% G2; 2.6% G3). Vomiting was reported by 21% and 0% of patients in the 5-HT3 and the NK1 group, respectively (p = 0.054). Among the 15 patients in the 5-HT3 group with nausea at cycle 1 who escalated to NK1 at cycle 2, nausea decreased from 100% to 53% (p = 0.022) and vomiting decreased from 47% to 13% (p = 0.046). Conclusions: The NK1 regimen improved vomiting control at cycle 1 and, when introduced at cycle 2, significantly improved both nausea and vomiting. The biased NK1 selection for higher-risk patients may have dampened the differences between groups at cycle 1. These findings support enhanced control of T-DXd-related nausea and vomiting with NK1RA.

Pan-cancer analysis of antibody-drug conjugate targets and putative predictors of treatment response.

BACKGROUND: Antibody-drug conjugates (ADCs) are a rapidly expanding class of compounds in oncology. Our goal was to assess the expression of ADC targets and potential downstream determining factors of activity across pan-cancer and normal tissues. MATERIALS AND METHODS: ADCs in clinical trials (n = 121) were identified through ClinicalTrials.gov, corresponding to 54 targets. Genes potentially implicated in treatment response were identified in the literature. Gene expression from The Cancer Genome Atlas (9000+ cancers of 31 cancer types), the Genotype-Tissue Expression database (n = 19,000 samples from 31 normal tissue types), and the TNMplot.com (n = 12,494 unmatched primary and metastatic samples) were used in this analysis. To compare relative expression across and within tumour types we used pooled normal tissues as reference. RESULTS: For most ADC targets, mRNA levels correlated with protein expression. Pan-cancer target expression distributions identified appealing cancer types for each ADC development. Co-expression of multiple targets was common and suggested opportunities for ADC combinations. Expression levels of genes potentially implicated in ADC response downstream of the target might provide additional information (e.g. TOP1 was highly expressed in many tumour types, including breast and lung cancers). Metastatic compared to primary tissues overexpressed some ADCs targets. Single sample "targetgram" plots were generated to visualise the expression of potentially competing ADC targets and resistance/sensitivity markers highlighting high inter-patient heterogeneity. Off-cancer target expression only partially explains adverse events, while expression of determinants of payload activity explained more of the observed toxicities. CONCLUSION: Our findings draw attention to new therapeutic opportunities for ADCs that can be tested in the clinic and our web platform (https://tnmplot.com) can assist in prioritising upcoming ADC targets for clinical development.

Tissue- and liquid biopsy-based biomarkers for immunotherapy in breast cancer.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy and now represent the mainstay of treatment for many tumor types, including triple-negative breast cancer and two agnostic registrations. However, despite impressive durable responses suggestive of an even curative potential in some cases, most patients receiving ICIs do not derive a substantial benefit, highlighting the need for more precise patient selection and stratification. The identification of predictive biomarkers of response to ICIs may play a pivotal role in optimizing the therapeutic use of such compounds. In this Review, we describe the current landscape of tissue and blood biomarkers that could serve as predictive factors for ICI treatment in breast cancer. The integration of these biomarkers in a "holistic" perspective aimed at developing comprehensive panels of multiple predictive factors will be a major step forward towards precision immune-oncology.

Geometric Analysis to Determine Kinking and Shortening of Bridging Stents After Branched Endovascular Aortic Repair.

PURPOSE: To evaluate bridging stent geometry in patients who underwent branched endovascular aortic repair (B-EVAR) and to correlate the outcomes with intrinsic bridging stent characteristics aiming to identify the stent(s) that guarantees the best performance. METHODS: Pre-operative and post-operative computed tomography images of all patients undergoing B-EVAR between September 2016 and April 2019 were retrospectively analyzed. Following geometrical features were measured: target vessel take-off angle (TOA); longitudinal stent shortening; shape index (SI), intended as ratio between minimum and maximum diameter of the lumen cross sections, averaged on three segments: zone 1 (proximal stented zone), zone 2 (intermediate), and zone 3 (distal). RESULTS: Thirty-eight branches (8 right (RRA) and 8 left renal arteries (LRA), 11 superior mesenteric arteries (SMA), 11 celiac trunks (CTR)) were treated. Fluency (Bard Peripheral Vascular), COVERA (Bard Peripheral Vascular), and VBX (WLGore&Assoc) stent-grafts were implanted in 10, 12, and 16 branches, respectively. Pre-operative TOA was more acute in RRA and LRA when compared to CTR and SMA, and straightened in post-operative configuration (109.86 ± 28.65° to 150.27 ± 21.0°; P < 0.001). Comparable values of SI among the stent types were found in zone 1 (P = 0.08), whereas higher SI in VBX group was detected in zones 2 (P < 0.001) and 3 (P < 0.001). The VBX group was also the most affected by stent shortening (11.12 ± 5.65%; P = 0.001). CONCLUSION: Our early experience showed that the VBX stent offers greater stent circularity than the other devices even if a greater shortening has been observed drawing attention with regards to the decision of the nominal stent length.