Postmastectomy Radiation Therapy: An ASTRO-ASCO-SSO Clinical Practice Guideline
Guidelines for post-mastectomy radiation include patients who received neoadjuvant therapy, with or without residual disease after treatment. A good topic to review.
Sacituzumab Govitecan in Untreated, Advanced Triple-Negative Breast Cancer
Author(s): Javier Cortés, M.D.1,2,3,4,5,6; Kevin Punie, M.D.7; Carlos Barrios, M.D.8; Sara A. Hurvitz, M.D.9; Andreas Schneeweiss, M.D.10,11; Joohyuk Sohn, M.D.12; Eriko Tokunaga, M.D.13; Adam Brufsky, M.D.14; Yeon Hee Park, M.D.15; Binghe Xu, M.D.16; Roberto Hegg, M.D.17; Mafalda Oliveira, M.D.18; Alessandra Fabi, M.D.19; Natalya Vaksman, Pharm.D.20; Theresa Valdez, Pharm.D.20; Xinrui Zhang, Ph.D.20; Catherine Lai, Pharm.D.20; Sara M. Tolaney, M.D.21; the ASCENT-03 Clinical Trial Investigators*;
Source: DOI: 10.1056/NEJMoa2511734
Dr. Anjan Patel's Thoughts
ASCENT-03 shows that in first-line, PD-1/PD-L1–ineligible advanced TNBC, sacituzumab improves PFS to 9.7 vs 6.9 months and extends median duration of response (DOR) to 12.2 vs 7.2 months, with similar overall response rate (ORR) (48% vs 46%) and immature overall survival (OS) (21.5 vs 20.2 months) Grade ≥3. Adverse events (AEs) were comparable (66% vs 62%), but sacituzumab had more neutropenia and diarrhea, fewer discontinuations (4% vs 12%), and early-cycle infection-related deaths in patients without primary G-CSF. For PD-1/PD-L1–ineligible mTNBC, SG offers more durable control than chemo with manageable myelosuppression — so consider SG first-line and start G-CSF early in higher-risk patients.
BACKGROUND
Patients with previously untreated, locally advanced, unresectable or metastatic triple-negative breast cancer who are not candidates for inhibitors of programmed cell death protein 1 (PD-1) or programmed death ligand 1 (PD-L1) have limited treatment options.
METHODS
In this international, phase 3, open-label, randomized trial, we enrolled patients with previously untreated, advanced triple-negative breast cancer who were not candidates for PD-1 or PD-L1 inhibitors owing to previous use or coexisting conditions. Patients had either PD-L1–negative tumors with a combined positive score (CPS; the number of PD-L1–staining tumor cells, lymphocytes, and macrophages divided by the total number of viable tumor cells, multiplied by 100) of less than 10 or PD-L1–positive tumors with a CPS of 10 or higher and were assigned in a 1:1 ratio to receive sacituzumab govitecan or chemotherapy (paclitaxel, nanoparticle albumin-bound paclitaxel, or gemcitabine plus carboplatin). The primary end point was progression-free survival, assessed by blinded independent central review. Secondary end points included overall survival, objective response, the duration of response, and safety. Research Summary Sacituzumab Govitecan in Advanced Triple-Negative Breast Cancer
RESULTS
Among 558 patients, median progression-free survival was 9.7 months (95% confidence interval [CI], 8.1 to 11.1) with sacituzumab govitecan and 6.9 months (95% CI, 5.6 to 8.2) with chemotherapy (stratified hazard ratio for disease progression or death, 0.62; 95% CI, 0.50 to 0.77; P
CONCLUSIONS
Sacituzumab govitecan led to significantly longer progression-free survival than chemotherapy among patients with advanced triple-negative breast cancer who were not candidates for treatment with PD-1 or PD-L1 inhibitors. The incidence of adverse events of grade 3 or higher with sacituzumab govitecan was similar to that with chemotherapy, but adverse events were common. (Funded by Gilead Sciences; ASCENT-03 ClinicalTrials.gov number, NCT05382299.)
Author Affiliations
1International Breast Cancer Center, Pangaea Oncology, Quiron Group, Barcelona; 2IOB Madrid, Institute of Oncology, Hospital Beata María Ana, Madrid; 3Oncology Department, Hospital Universitario Torrejón, Ribera Salud Group, Madrid; 4Universidad Europea de Madrid, Faculty of Biomedical and Health Sciences, Department of Medicine, Madrid; 5Medica Scientia Innovation Research, Barcelona; 6Medica Scientia Innovation Research, Ridgewood, NJ; 7Medical Oncology, Oncology Center Antwerp, Ziekenhuis aan de Stroom, Antwerp, Belgium; 8Latin American Cooperative Oncology Group, Porto Alegre, Brazil; 9Department of Medicine, University of Washington Medicine, Clinical Research Division, Fred Hutchinson Cancer Center, Seattle; 10Heidelberg University Hospital, Heidelberg, Germany; 11German Cancer Research Center, Heidelberg, Germany; 12Yonsei Cancer Center, Seoul, South Korea; 13National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan; 14Hillman Cancer Center, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh; 15Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; 16Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing; 17University of São Paulo, São Paulo; 18Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, Vall d’Hebron Barcelona Hospital Campus, Barcelona; 19Precision Medicine Unit in Senology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome; 20Gilead Sciences, Foster City, CA; 21Dana–Farber Cancer Institute, Harvard Medical School, BostonRelated Articles
First-Line Camizestrant for Emerging ESR1-Mutated Advanced Breast Cancer
Our site participated in this study, where patients were tested for ESR1 mutations via circulating tumor DNA (ctDNA). Those who tested positive were switched to camizestrant (Cami), which demonstrated improved progression-free survival.
Vepdegestrant, a PROTAC Estrogen Receptor Degrader, in Advanced Breast Cancer
Vepdegestrant is an oral proteolysis-targeting chimera (PROTAC) estrogen receptor (ER) degrader that directly utilizes the ubiquitin–proteasome system. It was compared to fulvestrant in patients who had received one prior line of hormonal therapy with a CDK4/6 inhibitor. Among patients with ESR1 mutations, Vepdegestrant demonstrated a median progression-free survival (PFS) of 5.0 months versus 2.1 months with fulvestrant. In the overall population, the median PFS was 3.8 months for Vepdegestrant and 3.6 months for fulvestrant, indicating that the drug showed particular efficacy in tumors harboring ESR1 mutations.
Elinzanetant for Vasomotor Symptoms from Endocrine Therapy for Breast Cancer
Elinzanitant, a neurokinin-targeted therapy, has been shown to reduce vasomotor symptoms compared to placebo. These symptoms are one of the reasons some of my patients discontinue aromatase inhibitor (AI) therapy, so Elinzanitant presents a promising alternative to help manage these side effects. Additionally, Fezolinetant is already approved and available on the market.
Overall Survival with Inavolisib in PIK3CA-Mutated Advanced Breast Cancer
The INAVO120 trial evaluated inavolisib + palbociclib–fulvestrant vs placebo + palbociclib–fulvestrant in patients with PIK3CA-mutated, HR+/HER2– advanced breast cancer progressing on or shortly after adjuvant endocrine therapy (ET). Inavolisib significantly improved overall survival (OS) (34.0 vs 27.0 mo) and progression-free survival (PFS) (17.2 vs 7.3 mo), with a higher objective response rate (ORR) (62.7% vs 28.0%) and longer DoR (19.2 vs 11.1 mo). Toxicities were manageable but included more hyperglycemia (63.4%), stomatitis (55.3%), GI, and ocular AEs. Bottom line: this triplet sets a new bar for first-line PIK3CA-mutant HR+ MBC, but we’ll need to stay vigilant about metabolic and mucosal side effects as we bring it into practice.