Safety and efficacy of pre-exposure prophylaxis with tixagevimab/cilgavimab (Evusheld) in patients with glomerular diseases who received rituximab.

Background: Patients on B-cell-depleting agents may have a suboptimal response to vaccination, placing them at a higher risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or suffering from a more severe prognosis. Indeed, available data on pre-exposure prophylaxis with tixagevimab/cilgavimab (Evusheld) in subjects with glomerular diseases (GDs) who received rituximab are limited. Methods: We conducted a prospective study analysing the safety and efficacy of tixagevimab/cilgavimab for pre-exposure prophylaxis in patients with GDs who received rituximab in the previous 12 months. The rates of symptomatic infections and hospitalizations were compared with those for patients with GD treated with rituximab who refused to receive tixagevimab/cilgavimab. Results: Tixagevimab/cilgavimab was administered to 22 patients (12 females, mean age 58.4 ± 19.6 years) with GD diagnoses including membranous nephropathy, lupus nephritis, anti-neutrophil cytoplasmic antibody-associated vasculitis and focal segmental glomerulosclerosis. No patient treated with tixagevimab/cilgavimab experienced symptomatic infection with SARS-CoV-2 during the follow-up (mean observation time of follow-up was 112 ± 23 days), while 11 of 28 controls (39.3%) reported a symptomatic infection (P = .0001), requiring hospitalization in 2 cases. Reported adverse events were mild, namely self-limiting headache [4], discomfort at the injection site [3], flu-like symptoms/myalgia [3] and fever [1]. No serious adverse events (e.g. cardiac events, anaphylaxis) were reported. Conclusion: Pre-exposure prophylaxis with tixagevimab/cilgavimab seems safe and lowered the risk of symptomatic SARS-CoV-2 infection by ≈40% in vaccinated subjects with GD who received anti-CD20 therapy. Possible applications in the subset of patients who need immunosuppressive therapy, especially with rituximab, in a pandemic setting might be envisaged.

Exploratory analysis of the effect of a dexamethasone-sparing regimen for prophylaxis of cisplatin-induced emesis on food intake (LUNG-NEPA study).

We demonstrated the non-inferiority of a dexamethasone (DEX)-sparing (single-dose) regimen with NEPA, a netupitant/palonosetron fixed combination, for preventing chemotherapy-induced nausea and vomiting (CINV) caused by cisplatin. This pre-planned exploratory analysis assessed the effect of the DEX-sparing regimen on a patient's food intake. Chemotherapy-naïve patients undergoing cisplatin (≥ 70 mg/m2) were given NEPA and DEX (12 mg) on day 1 and randomized to receive either no further DEX (DEX1), or oral DEX (4 mg BID) on days 2-4 (DEX4). Patient-reported endpoint maintenance of usual daily food intake was assessed during the 5-days post-chemotherapy. The relationship between usual daily food intake and CINV control, pre-chemotherapy self-rated food intake and BMI-adjusted weight loss (WL) were evaluated. One-hundred fifty-two patients (76/group) were assessable. The proportion of patients reporting maintenance of usual daily food intake was similar in both groups: 69.7% (95% CI, 58.6-78.9) for DEX1 vs. 72.4% (95% CI, 61.4-81.2) for DEX4. Only CINV control was significantly associated with maintenance of usual daily food intake (P ≤ 0.001) during the overall phase. The DEX-sparing regimen does not adversely affect patient-reported daily food intake post-chemotherapy. The current analysis adds further insights into antiemetic efficacy of DEX sparing beyond day 1 in the challenging setting of cisplatin.Trial registration: The parent study was registered on ClinicalTrials.gov (NCT04201769).

Evaluating the impact of chemotherapy-induced nausea and vomiting on daily functioning in patients receiving dexamethasone-sparing antiemetic regimens with NEPA (netupitant/palonosetron) in the cisplatin setting: results from a randomized phase 3 study.

BACKGROUND: The non-inferiority of dexamethasone (DEX) on day 1, with or without low-dose DEX on days 2 and 3, combined with oral NEPA (netupitant/palonosetron), compared with the guideline-consistent use of DEX was demonstrated in cisplatin. Here, we complete the analysis by assessing the impact of emesis on daily lives of patients receiving DEX-sparing regimens using the Functional Living Index-Emesis (FLIE). METHODS: Chemotherapy-naïve patients undergoing cisplatin (≥70 mg/m2), were given NEPA and DEX (12 mg) on day 1 and randomized to receive either 1) no further DEX (DEX1), 2) oral DEX (4 mg daily) on days 2-3 (DEX3), or 3) DEX (4 mg twice daily) on days 2-4 (DEX4; control). Patients completed the FLIE questionnaire on day 6 of cycle 1. Endpoints included the FLIE nausea domain, vomiting domain, and overall combined domain scores, as well as the proportion of patients with no impact on daily life (NIDL; overall score > 108). This was a protocol-planned analysis. RESULTS: In the DEX1 group, no significant differences were observed in the FLIE nausea score (48.9 [±1.8; SE] vs. 53.7 [±1.5]), vomiting score (56.6 [±1.4] vs. 58.7 [±0.8]) and overall score (105.6 [±2.8] vs.112.4 [±1.9]) versus DEX4 control; similar results were observed in the DEX3 group for nausea score (49.6 [±1.7]), vomiting score (58.2 [±1]) and overall score (107.8 [±2.4]) versus control. There were no significant between-group differences in the proportion of patients reporting NIDL. CONCLUSION: Reducing DEX, when administered with NEPA, does not seem to adversely impact the daily functioning in patients undergoing cisplatin. TRIAL REGISTRATION: ClinicalTrials.gov NCT04201769 . Registration date: 17/12/2019 - Retrospectively registered.

Dexamethasone-Sparing Regimens with Oral Netupitant and Palonosetron for the Prevention of Emesis Caused by High-Dose Cisplatin: A Randomized Noninferiority Study.

BACKGROUND: To reduce the overall exposure to dexamethasone (DEX) in patients receiving cisplatin-based chemotherapy, we evaluated the noninferiority of DEX on day 1, with or without low-dose DEX on days 2 and 3, combined with an oral fixed-dose combination of netupitant and palonosetron (NEPA), compared with the guideline-consistent use of 4-day DEX. PATIENTS AND METHODS: In this open-label, multicenter study, chemotherapy-naïve patients undergoing high-dose cisplatin (≥70 mg/m2 ), were given NEPA and DEX (12 mg) on day 1 and randomized (1:1:1 ratio) to receive either (a) no further DEX (DEX1), (b) oral DEX (4 mg daily) on days 2-3 (DEX3), or (c) DEX (4 mg twice daily) on days 2-4 (DEX4). The primary efficacy endpoint was complete response (CR: no emesis and no rescue medication) during the 5-day overall phase. The noninferiority margin was set at -15% difference (DEX1 or DEX3 minus DEX4). Secondary efficacy endpoints included complete protection (CP: CR and none or mild nausea). RESULTS: Two-hundred twenty-eight patients, 76 in each arm, were assessable. Noninferiority was met for both DEX-sparing regimens and the reference arm, with overall phase CR rates of 76.3% in each of the DEX1 and DEX3 arms and 75.0% in the DEX4 arm (95% confidence interval, -12.3% to 15% for each comparison). During the overall phase, CP rates were similar between groups. CONCLUSION: A simplified regimen of NEPA plus single-dose DEX offers comparable chemotherapy-induced nausea and vomiting prevention throughout 5 days post-chemotherapy with the advantage of sparing patients additional doses of DEX in the high-emetic-risk setting of cisplatin-based chemotherapy. IMPLICATIONS FOR PRACTICE: Dexamethasone (DEX) has traditionally played an integral role in the management of chemotherapy-induced emesis. Although generally considered safe, even short-term DEX use is associated with various side effects, and some evidence suggests that concurrent steroids may reduce the efficacy of immunotherapies. This study demonstrates comparable antiemetic control during the 5 days post-chemotherapy with a simplified regimen of netupitant/palonosetron plus single-dose DEX versus the standard 4-day DEX reference treatment in high-dose cisplatin. This represents a clinically relevant achievement as it not only simplifies antiemetic prophylaxis but also offers an opportunity to appropriately use in patients where caution with corticosteroid use is advised.

Sexual function and sex hormones in breast cancer patients.

PURPOSE: Breast cancer patients (BCP) are at risk of female sexual dysfunction (FSD). Our aim was to clarify the effects of treatment strategies, and steroid hormones levels on FSD. METHODS: We enrolled 136 BCP (46.9 ± 0.8 years), and 122 completed questionnaires. BCP were divided into four groups: 22 women with advanced breast cancer on neoadjuvant therapy (NAT), 48 on adjuvant therapy (AT), 30 taking hormonal therapy (HT) and 22 with metastatic cancer on first line chemotherapy (FLT). Fifty-eight healthy women (43 ± 2.8 years) were enrolled as controls. FSD was evaluated by FSFI, and sexual distress was assessed with FSDS-R. We have collected demographic data, laboratory values, and LH, FSH, total testosterone (T), and estradiol (E2) levels. RESULTS: BCP showed a prevalence of FSD of 69%, total FSFI score was 17. FSDS-R was 8.3. FSD had a prevalence of 72 % in NAT, 65% in AT, 77% in metastatic BCP under FLT, 67% in HT, compared with a prevalence of 20% in controls. BCP showed lower E2 than normal values, as well as T. LH and FSH were significantly elevated than normal values. Total FSFI score was positively correlated with T in 122 BCP, no significant correlation was found between E2 and FSFI. Significant differences were found between NAT and HT in lubrication, pain domains and total FSDS-R score, AT and HT in pain domain, AT and NAT in lubrication domain. CONCLUSIONS: BCP are at high risk of developing FSD both for treatment choice and hormonal status, but they have not sexually related personal distress.