Sacituzumab govitecan as second-line treatment for metastatic triple-negative breast cancer—phase 3 ASCENT study subanalysis

Breast cancer; Second-line treatmentCáncer de mama; Tratamiento de segunda líneaCàncer de mama; Tractament de segona líniaPatients with triple-negative breast cancer (TNBC) who relapse early after (neo)adjuvant chemotherapy have more aggressive disease. In the ASCENT trial, sacituzumab govitecan (SG), an antibody-drug conjugate composed of an anti-Trop–2 antibody coupled to SN-38 via a hydrolyzable linker, improved outcomes over single-agent chemotherapy of physician’s choice (TPC) in metastatic TNBC (mTNBC). Of 468 patients without known baseline brain metastases, 33/235 vs 32/233 patients (both 14%) in the SG vs TPC arms, respectively, received one line of therapy in the metastatic setting and experienced disease recurrence ≤12 months after (neo)adjuvant chemotherapy. SG prolonged progression-free survival (median 5.7 vs 1.5 months [HR, 0.41; 95% CI, 0.22–0.76]) and overall survival (median 10.9 vs 4.9 months [HR, 0.51; 95% CI, 0.28–0.91]) vs TPC, with a manageable safety profile in this subgroup consistent with the overall population. In this second-line setting, as with later-line therapy, SG improved survival over conventional chemotherapy for patients with mTNBC.This study was sponsored by Gilead Sciences, Inc

Sacituzumab Govitecan in Hormone Receptor–Positive/Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer

Sacituzumab govitecán; Cáncer de mama metastásicoSacituzumab govitecan; Càncer de mama metastàticSacituzumab govitecan; Metastatic breast cancerPURPOSE Hormone receptor–positive (HR+) human epidermal growth factor receptor 2–negative (HER2–) endocrine-resistant metastatic breast cancer is treated with sequential single-agent chemotherapy with poor outcomes. Sacituzumab govitecan (SG) is a first-in-class antibody-drug conjugate with an SN-38 payload targeting trophoblast cell-surface antigen 2, an epithelial antigen expressed in breast cancer. METHODS In this global, randomized, phase III study, SG was compared with physician's choice chemotherapy (eribulin, vinorelbine, capecitabine, or gemcitabine) in endocrine-resistant, chemotherapy-treated HR+/HER2– locally recurrent inoperable or metastatic breast cancer. The primary end point was progression-free survival (PFS) by blinded independent central review. RESULTS Patients were randomly assigned to receive SG (n = 272) or chemotherapy (n = 271). The median age was 56 years, 95% had visceral metastases, and 99% had a prior cyclin-dependent kinase 4/6 inhibitor, with three median lines of chemotherapy for advanced disease. Primary end point was met with a 34% reduction in risk of progression or death (hazard ratio, 0.66 [95% CI, 0.53 to 0.83; P = .0003]). The median PFS was 5.5 months (95% CI, 4.2 to 7.0) with SG and 4.0 months (95% CI, 3.1 to 4.4) with chemotherapy; the PFS at 6 and 12 months was 46% (95% CI, 39 to 53) v 30% (95% CI, 24 to 37) and 21% (95% CI, 15 to 28) v 7% (95% CI, 3 to 14), respectively. Median overall survival (first planned interim analysis) was not yet mature (hazard ratio, 0.84; P = .14). Key grade ≥ 3 treatment-related adverse events (SG v chemotherapy) were neutropenia (51% v 38%) and diarrhea (9% v 1%). CONCLUSION SG demonstrated statistically significant PFS benefit over chemotherapy, with a manageable safety profile in patients with heavily pretreated, endocrine-resistant HR+/HER2– advanced breast cancer and limited treatment options

Safety analyses from the phase 3 ASCENT trial of sacituzumab govitecan in metastatic triple-negative breast cancer

Breast cancer; Drug safetyCàncer de mama; Seguretat dels medicamentsCáncer de mama; Seguridad de los medicamentosSacituzumab govitecan (SG) is an anti-Trop-2 antibody-drug conjugate with an SN-38 payload. In the ASCENT study, patients with metastatic triple-negative breast cancer (mTNBC) relapsed/refractory to ≥2 prior chemotherapy regimens (≥1 in the metastatic setting), received SG or single-agent treatment of physician’s choice (eribulin, vinorelbine, capecitabine, or gemcitabine). This ASCENT safety analysis includes the impact of age and UGT1A1 polymorphisms, which hinder SN-38 detoxification. SG demonstrated a manageable safety profile in patients with mTNBC, including those ≥65 years; neutropenia/diarrhea are key adverse events (AE). Patients with UGT1A1 *28/*28 genotype versus those with 1/*28 and *1/*1 genotypes had higher rates of grade ≥3 SG-related neutropenia (59% vs 47% and 53%), febrile neutropenia (18% vs 5% and 3%), anemia (15% vs 6% and 4%), and diarrhea (15% vs 9% and 10%), respectively. Individuals with UGT1A1 *28/*28 genotype should be monitored closely; active monitoring and routine AE management allow optimal therapeutic exposure of SG.This study was sponsored by Immunomedics, Inc., a subsidiary of Gilead Sciences, Inc. We thank the ASCENT patients, their caregivers, study investigators, and team members. We thank William A. Wegener, MD, PhD, Robert M. Sharkey, PhD, and Pius Maliakal, PhD, former employees of Immunomedics, for their contributions to the development of the ASCENT protocol and the clinical development of sacituzumab govitecan. Medical writing and editorial assistance were provided by Robert Rydzewski, MS, CMPP, and Shala Thomas, PhD, CMPP, of Team 9 Science, and funded by Immunomedics, Inc., a subsidiary of Gilead Sciences, Inc

Health-related quality of life in the phase III ASCENT trial of sacituzumab govitecan versus standard chemotherapy in metastatic triple-negative breast cancer

Quality of life; Sacituzumab govitecan; Triple-negative breast neoplasmsQualitat de vida; Sacituzumab govitecan; Neoplàsies de mama triple negatiuCalidad de vida; Sacituzumab govitecan; Neoplasias de mama triple negativoBackground The antibody–drug conjugate sacituzumab govitecan (SG) prolongs progression-free survival and overall survival in patients with refractory/relapsed metastatic triple-negative breast cancer (mTNBC). Here, we investigated its effect on health-related quality of life (HRQoL). Methods This analysis was based on the open-label phase III ASCENT trial (NCT02574455). Adults with refractory/relapsed mTNBC who had received ≥2 prior systemic therapies (≥1 in the metastatic setting) were randomised 1:1 to SG or treatment of physician's choice (TPC; capecitabine, eribulin, vinorelbine, or gemcitabine). HRQoL was assessed on day 1 of each treatment cycle using the EORTC QLQ-C30. Score changes from baseline were analysed using linear mixed-effect models for repeated measures. Stratified Cox regressions evaluated time to first clinically meaningful change of HRQoL. Results The analysis population comprised 236 patients randomised to SG and 183 to TPC. For global health status (GHS)/QoL, physical functioning, fatigue, and pain, changes from baseline were superior for SG versus TPC. Compared with TPC, SG was inferior regarding changes from baseline for nausea/vomiting and diarrhoea but non-inferior for other QLQ-C30 domains. Median time to first clinically meaningful worsening was longer for SG than for TPC for physical functioning (22.1 versus 12.1 weeks, P < 0.001), role functioning (11.4 versus 7.1 weeks, P < 0.001), fatigue (7.7 versus 6.0 weeks, P < 0.05), and pain (21.6 versus 9.9 weeks, P < 0.001). Conclusions SG was generally associated with greater improvements and delayed worsening of HRQoL scores compared with TPC. This supports the favourable profile of SG as an mTNBC treatment.This work was sponsored by Gilead Sciences

Rupture de la tolérance à l'antigène de surface du virus de l'hépatite B par l'immunisation génétique (modèle d'étude pour l'immunothérapie des hépatites B chroniques)

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Adjuvant Trastuzumab Emtansine (T-DM1) and Concurrent Radiotherapy for Residual Invasive HER2-positive Breast Cancer: Single-center Preliminary Results

International audienceObjectives:The treatment of nonmetastatic HER2-positive breast cancer with residual invasive disease using concurrent Trastuzumab emtansine (T-DM1) and radiotherapy appears to be an effective option. Our aim was to evaluate the acute side effects of this treatment regime.Methods:Fourteen patients were treated between March 2019 and April 2020 concurrent T-DM1 and radiotherapy. Left ventricular ejection fraction was assessed at baseline, before and after radiotherapy. All toxicities were evaluated using Common Terminology Criteria of Adverse Events (CTCAE) version 3.0.Results:The median age was 55 years (range 36 to 72). All patients received total dose of 50 Gy for the breast/ chest wall, 10 patients got lymph node irradiation, 4 patients received an additional tumor bed boost. The most common side effect was grade 1 radiodermatitis. A reversible grade 2 left ventricular ejection fraction decrease occurred in 2 patients. During our examination 3 patients showed alanine aminotransferases increase after the cycle 4 of T-DM1, 1 patient had grade 1, 1 patient grade 2, and 1 patient grade 3 alanine aminotransferase increases.Conclusions:The acute toxicity rate especially focusing on skin and cardiac toxicity were assumed acceptable in our cohort. To safely administer this concomitant treatment, further examination and prospective data are needed

Pertuzumab and Trastuzumab Combination with Concomitant Locoregional Radiotherapy for the Treatment of Breast Cancers with HER2 Receptor Overexpression

Background: The combination of pertuzumab and trastuzumab dual HER2 blockade with concomitant curative dose locoregional breast radiotherapy in patients with metastatic breast cancer is an important part of treatment strategy. Methods: This was a retrospective study conducted at the Institut Curie on all patients treated concomitantly with pertuzumab/trastuzumab and locoregional breast radiotherapy. Toxicity was evaluated according to the NCICTCAEv4.0. Overall survival, progression-free survival and locoregional recurrence-free survival were evaluated in metastatic patients who were initially well controlled by chemotherapy, for whom local treatment was decided by the multidisciplinary team. Results: Fifty-five patients treated between October 2013 and December 2019 were included, with a median follow-up of 4.1 years. The median age was 53 years (range: 28–81). All patients received curative dose radiotherapy (RT) concomitantly with pertuzumab and trastuzumab (Pertu/Trastu). The median radiation dose was 50 Gy. Safety evaluation did not reveal any significant adverse effects, with 3 cases of grade 3 radiodermatitis (5.4%), but no significant gastrointestinal or cardiac toxicity. The mean difference in LVEF before any chemotherapy and after radiotherapy was −2.43% (p &lt; 0.01). Conclusions: This study demonstrates that the combination of locoregional breast RT with dual HER2 blockade by Pertu/Trastu was very well tolerated, suggesting that RT can be safely administered to patients with HER2-positive breast cancer

Radiotherapy in the management of non-metastatic inflammatory breast cancers: A retrospective observational study

International audience(1) Background: Inflammatory breast cancers (IBC) are characterized by a poor prognosis. This retrospective study aims to describe the clinical outcomes of non-metastatic IBC patients treated with a multidisciplinary approach with neo-adjuvant chemotherapy, surgery, and radiotherapy. (2) Methods: This single-center retrospective study included all women patients diagnosed with non-metastatic IBC between January 2010 and January 2018 at the Institut Curie (Paris, France) and treated with neoadjuvant chemotherapy, surgery, and radiotherapy. Overall survival (OS), disease-free survival (DFS), and locoregional free survival (LRRFS) were calculated from the time of diagnosis. Prognostic factors for patient survival were analyzed based on univariate and multivariate regressions. (3) Results: We identified 113 patients with a median age of 51 years. 79.7% had node-positive tumors; triple-negative breast cancers (TNBC) represented 34.6% of the cases. A large majority of patients (91.2%) received adjuvant post-mastectomy while ten patients (8.8%) received preoperative radiotherapy. Non-pathological complete response (non-pCR) was observed in 67.3% of patients. Radiotherapy delivered a median dose of 50 Gy to the breast or the chest wall in 25 fractions. With a median follow-up of 54 months, 5-year OS, DFS and LRRFS were 78% (CI: 70.1–86.8%), 68.1% (59.6–77.7%), and 85.2% (78.4–92.7%), respectively. In multivariate analysis, non-pCR was an adverse prognosis factor for OS, DFS, and LRRFS; pre-operative radiotherapy was an adverse prognosis factor for OS and DFS. Radiation-related adverse events were limited to acute skin toxicity (22% of Grade 2 and 2% of grade 3 dermatitis); no late radiation-induced toxicity was reported. (4) Conclusions: High locoregional control could be achieved with multidisciplinary management of non-metastatic IBC, suggesting the anti-tumor efficacy of radiotherapy in this rare but pejorative clinicopathological presentation. While comparing favorably with historical cohorts, OS and DFS could be potentially improved in the future with the use of new systemic treatments, such as PARP-inhibitors or immunotherapy