Doublet or Triplet Antiemetic Prophylaxis for Nausea and Vomiting Induced by Trastuzumab Deruxtecan: an Open-Label, Randomized, and Multicenter Exploratory Phase 2 Study.

Background: Trastuzumab deruxtecan is classified as an anticancer agent that poses a moderate emetic risk in the international guidelines for antiemetic therapy. The guidelines recommend emesis prophylaxis using a two-drug combination therapy comprising a 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA) and dexamethasone (DEX). However, the high incidence of nausea and vomiting associated with trastuzumab deruxtecan is problematic. The National Comprehensive Cancer Network guideline version 1.2023 classified trastuzumab deruxtecan as having a high risk of emesis and changed its recommendation to a triplet regimen including a neurokinin-1 receptor antagonist (NK1RA). However, the emetogenic potential of trastuzumab-deruxtecan and the optimal antiemetic prophylaxis are controversial. Hence, this exploratory phase 2 study aimed to assess the efficacy and safety of treatment comprising 5-HT3RA and DEX with or without a NK1RA in preventing trastuzumab deruxtecan-induced nausea and vomiting. Methods: We conducted an open-label and randomized exploratory phase 2 study at 14 centers in Japan. Patients with breast cancer who were scheduled to receive trastuzumab deruxtecan were enrolled in this study. The patients were randomly assigned to receive granisetron and DEX (arm GD) or granisetron, DEX, and aprepitant (fosaprepitant; arm GDA). The primary endpoint was complete response (CR; no emesis or no rescue therapy) during the overall phase (120 h after the start of trastuzumab deruxtecan). Results: Between September 2020 and March 2023, 40 patients were randomly assigned to the GD (n = 19) or GDA (n = 21) arm. In the GDA arm, one patient who did not complete the use of the rescue medication listed in the diary was excluded from the efficacy analysis, which included the use of rescue medication. The CR rates during the overall phase were 36.8% and 70.0% in the GD and GDA arms, respectively (odds ratio 0.1334; 95% confidence interval [CI]: 0.0232-0.7672; P = 0.0190), with a difference of 33.2%. No grade 3 or 4 toxicity related to antiemetic therapy was observed. Conclusions: Patients receiving trastuzumab deruxtecan require triple therapy, including mandatory NK1RA administration.

Neoadjuvant chemotherapy using nanoparticle albumin-bound paclitaxel plus trastuzumab and pertuzumab followed by epirubicin and cyclophosphamide for operable HER2-positive primary breast cancer: a multicenter phase II clinical trial (PerSeUS-BC04).

BACKGROUND: Nanoparticle albumin-bound paclitaxel (nab-PTX) is a promising antibody partner for anti-human epidermal growth factor receptor 2 (HER2). We performed neoadjuvant chemotherapy (NAC) for HER2-positive breast cancer (BC) using nab-PTX plus trastuzumab (T-mab) and pertuzumab (P-mab), followed by epirubicin and cyclophosphamide (EC). METHODS: In this multicenter phase II clinical trial (January 2019-July 2020), patients with stage I (T1c)-IIIB HER2-positive primary BC were treated with four cycles of nab-PTX plus T-mab and P-mab, followed by four cycles of EC. The primary endpoint was the pathological complete response (pCR) rate. Secondary endpoints were clinical response rate (RR), adverse events (AE), and tumor-infiltrating lymphocytes (TILs) in biopsy samples. RESULTS: In total, 43 patients were enrolled (mean age, 54 years). Twenty-two patients had HER2, and 21 patients had luminal/HER2-subtypes. The overall pCR rate was 53.5% (23/43, 95% CI: 42.6-64.1%, p = 0.184), whilst the pCR for HER2 was 68.2% (15/22, 95% CI: 45.1-86.1) and 38.1% for luminal/HER2 (8/21, 95% CI: 18.1-61.6%). The RR was 100% [clinical (c) CR:25, partial response (PR): 18]. AEs (≥ G3) included neutropenia (23.3%), leukopenia (7.0%), liver dysfunction (7.0%), and peripheral neuropathy (4.7%) when nab-PTX was administered. EC administration resulted in leukopenia (34.2%), neutropenia (31.6%), and febrile neutropenia (15.8%). The TILs in preoperative biopsy samples were significantly higher in pCR compared to non-pCR samples. CONCLUSION: Nab-PTX plus T-mab and P-mab induced a high pCR rate in HER2-positive BC, particularly in the HER2-subtype. Given that AEs are acceptable, this regimen is safe and acceptable as NAC for HER2-positive BC.

Breast reconstruction using a tissue expander after enucleation of a giant fibroadenoma: A case report.

INTRODUCTION: Fibroadenomas are among the most common benign tumors in women. Juvenile giant fibroadenomas account for nearly 0.5% of all fibroadenomas. Due to its size, a giant juvenile fibroadenoma leaves a large defect or deformity after its resection. The optimal surgical management strategy for giant juvenile fibroadenomas remains unclear. Here, we report a case of successful breast reconstruction without residual deformity through gradual deflation of a saline-filled tissue expander after resection of a giant juvenile fibroadenoma. PRESENTATION OF CASE: A 14-year-old girl with a growing tumor in her left breast presented to a private clinic. Given that the tumor was 8 cm in size, phyllodes could not be ruled out. Consequently, she was referred to our hospital for further examination and treatment. Core needle biopsy confirmed the tumor to be a fibroadenoma. We resected the tumor and inserted a tissue expander filled with 120 mL of saline, matching the area of the large defect caused by tumor resection. We removed approximately 25 mL of saline every 3 weeks to aid normal mammary tissue enlargement. After completely draining saline from the tissue expander and confirming an acceptable enlargement of the residual mammary gland, we performed an operation to remove the tissue expander. Follow-up revealed that the symmetry and contour of the breast were excellent after the second operation. CONCLUSIONS: Our observations suggest that using a tissue expander to enlarge normal mammary tissue may help reconstruct large defects caused by excision of benign tumors.

Total laparoscopic excision of retroperitoneal ganglioneuroma: A case report.

INTRODUCTION: Ganglioneuromas are rare benign tumors originating from neural crests and typically affect young adults. The most frequent locations are the posterior mediastinum, retroperitoneum and adrenal gland. In general, retroperitoneal ganglioneuromas are discovered incidentally or by mass effect. In the literature, the number of retroperitoneal masses reported is quite limited. We report a case of laparoscopic excision of a retroperitoneal ganglioneuroma. PRESENTATION OF CASE: The patient was a 40-year-old woman who visited a nearby clinic with anorexia and vomiting. She was referred to our hospital after the detection of an abdominal mass. Enhanced computed tomography(CT) showed a lobule mass of 107 × 42 mm in size, with internal inhomogeneity and mild delayed enhancement on the retroperitoneal side of the left abdominal lesion. Magnetic resonance imaging(MRI) showed a mass with low intensity and partial high intensity on T2 weighted Image (T2WI). In addition, positron emission tomography CT(PET-CT) detected slight fluorodeoxyglucose (FDG) accumulation (standardized uptake value(SUV) max: 3.01) in the same lesion. Based on these findings, we suspected a retroperitoneal tumor. Laparoscopic excision was performed via 5 ports. The extracted tissue was a well-defined mass of 110 × 70 mm. The tumor in our case exceeded 10 cm. The pathological diagnosis was ganglioneuroma, with no obvious malignancy. DISCUSSION: It was suggested that adaptation of laparoscopic surgery should be considered based on the observation of organ invasion or vessel invasion and adhesion around the tumor, rather than based on the diameter of the tumor. CONCLUSION: This approach is less invasive than conventional laparotomy methods and achieves good cosmetic outcomes. Thus, totally laparoscopic procedures should be considered more often for the treatment of retroperitoneal tumors.

The mode of progressive disease affects the prognosis of patients with metastatic breast cancer.

BACKGROUND: According to the Response Evaluation Criteria in Solid Tumors (RECIST), progressive disease (PD) is diagnosed under two conditions: an increase in size of pre-existing lesions (IS) and the appearance of new lesions (NL). We retrospectively investigated the difference in the prognosis between IS and NL. METHODS: Patients receiving drug therapies for metastatic breast cancer between 2004 and 2015 at our institution were reviewed. The survival time after NL and IS was compared and the frequency of NL with each drug calculated. RESULTS: For the 107 eligible patients, the survival time after NL at second-line chemotherapy was significantly worse than after IS (median survival time 4.3 months vs. 20.3 months, p = 0.0048). Maintenance therapy with bevacizumab or trastuzumab had a high frequency of NL (88.9%), and third-line eribulin had a low frequency of NL (16.7%). A multivariate analysis showed that NL at second-line chemotherapy was not an independent risk factor (hazard ratio 1.02, 95%; confidence interval 0.54-1.93, p = 0.95) for the total survival time. CONCLUSIONS: Patients with IS had a better survival after PD than those with NL. We may be able to avoid changing drug therapy for patients without NL and allow them to continue drug therapy for longer.