FOSTER CITY, CA, USA I July 27, 2023 I Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the European Commission (EC) approved Trodelvy® (sacituzumab govitecan) as a monotherapy for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-negative breast cancerHER2-negative breast cancer who have received endocrine-based therapy, and at least two additional systemic therapies in the advanced setting. The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products and is based on the Phase 3 TROPiCS-02 study, in which Trodelvy demonstrated a statistically significant and clinically meaningful overall survival (OS) benefit of 3.2 months versus comparator single-agent chemotherapy (treatment of physician’s choice; TPC) (median OS: 14.4 months vs. 11.2 months; hazard ratio [HR]=0.79; 95% CI: 0.65-0.96; p=0.02). Trodelvy also demonstrated a 34% reduction in risk of disease progression or death (median PFS: 5.5 versus 4.0 months; HR: 0.66; 95% CI: 0.53-0.83; p=0.0003). Three times as many people treated with Trodelvy were progression-free at one year versus those treated with chemotherapy (21% versus 7%). “Trodelvy could change the outlook for women with pre-treated HR+/HER2- metastatic breast cancerHR+/HER2- metastatic breast cancer by replacing the standard-of-care chemotherapy that has been their only option for decades,” said Bill Grossman, M.D., Ph.D., Senior Vice President, Therapeutic Area Head, Gilead Oncology. “We look forward to working with European authorities to ensure access for these patients who need new treatment options.” “Women living with pre-treated HR+/HER2- metastatic breast cancerHR+/HER2- metastatic breast cancer are focused on time with their loved ones and do not want to worry about running out of treatment options,” said Eva Schumacher-Wulf, Chief Editor, Mamma Mia! Magazine and Metastatic Breast Cancer Patient. “We welcome the approval of this needed new option that gives pre-treated HR+/HER2- metastatic patients the potential for a longer life.” In the TROPiCS-02 study, Trodelvy also significantly improved additional secondary endpoint measures, including objective response rate and time to deterioration (TTD) assessed by the Global Health Status/Quality of Life and Fatigue scale per EORTC-QLQ-C30. No statistically significant difference in TTD in Pain Scale was observed. The safety profile for Trodelvy is well-characterized and consistent with prior studies, with no new safety signals identified in this patient population. In TROPiCS-02, the most frequent serious adverse reactions (>1%) were diarrhea (5%), febrile neutropenia (4%), neutropenia (3%), and abdominal pain, colitis, neutropenic colitis, pneumonia, and vomiting (each 2%). No patients treated with Trodelvy in TROPiCS-02 experienced interstitial lung disease (ILD). In the TROPiCS-02 study, the discontinuation rate due to adverse reactions was 6% for Trodelvy and 4% for patients on single-agent chemotherapy. Trodelvy is also recommended as a Category 1, preferred treatment for metastatic HR+/HER2- breast cancerHR+/HER2- breast cancer by the National Comprehensive Cancer Network® (NCCN®) as defined in the Clinical Practice Guidelines in Oncology (NCCN Guidelines®).ii Trodelvy has a Boxed Warning for severe or life-threatening neutropenia and severe diarrhea; please see below for additional Important Safety Information. About the TROPiCS-02 Study
The TROPiCS-02 study is a global, multicenter, open-label, Phase 3 study, randomized 1:1 to evaluate Trodelvy versus physicians’ choice of chemotherapy (eribulin, capecitabine, gemcitabine, or vinorelbine) in 543 patients with HR+/HER2- metastatic breast cancerHR+/HER2- metastatic breast cancer who were previously treated with endocrine therapy, CDK4/6 inhibitorCDK4/6 inhibitor and two to four lines of chemotherapy for metastatic disease. The primary endpoint is progression-free survival per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by blinded independent central review (BICR) for participants treated with Trodelvy compared to those treated with chemotherapy. Secondary endpoints include overall survival, overall response rate, clinical benefit rate and duration of response, as well as assessment of safety and tolerability and quality of life measures. In the study, HER2 negativity was defined per American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) criteria as immunohistochemistry (IHC) score of 0, IHC 1+ or IHC 2+ with a negative in-situ hybridization (ISH) test. More information about TROPiCS-02 is available at https://clinicaltrials.gov/ct2/show/NCT03901339. Trodelvy is also approved in the U.S. for the treatment of adult patients with unresectable locally advanced or metastatic HR+/HER2- breast cancerHR+/HER2- breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting and has an accelerated approval for treatment of certain patients with second-line metastatic urothelial cancer; see below for full U.S. indication statements. Important Safety Information for Trodelvy as Included in the U.S. Prescribing Information for Trodelvy Recommendations for the use of Trodelvy in the EU (including final safety information for prescribers) have been assessed as part of the Marketing Authorization Application and are detailed in full in the EU SmPC. Recommendations for the use of Trodelvy in other countries outside of the U.S. are subject to assessment by the relevant local regulatory authority as part of the registration/marketing authorization process. Once approved, recommendations are detailed in the local prescribing information. In the United States, Trodelvy is indicated for the treatment of: U.S. Important Safety Information for Trodelvy
Increased Risk of Adverse Reactions in Patients with Reduced UGT1A1 Activity: Patients homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia and may be at increased risk for other adverse reactions with Trodelvy. The incidence of Grade 3-4 neutropenia was 58% in patients homozygous for the UGT1A1*28, 49% in patients heterozygous for the UGT1A1*28 allele, and 43% in patients homozygous for the wild-type allele. The incidence of Grade 3-4 anemia was 21% in patients homozygous for the UGT1A1*28 allele, 10% in patients heterozygous for the UGT1A1*28 allele, and 9% in patients homozygous for the wild-type allele. Closely monitor patients with known reduced UGT1A1 activity for adverse reactions. Withhold or permanently discontinue Trodelvy based on clinical assessment of the onset, duration and severity of the observed adverse reactions in patients with evidence of acute early-onset or unusually severe adverse reactions, which may indicate reduced UGT1A1 function. Embryo-Fetal Toxicity: Based on its mechanism of action, Trodelvy can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. Trodelvy contains a genotoxic component, SN-38, and targets rapidly dividing cells. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Trodelvy and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with Trodelvy and for 3 months after the last dose. In the pooled safety population, the most common (≥ 25%) adverse reactions including laboratory abnormalities were decreased leukocyte count (84%), decreased neutrophil count (75%), decreased hemoglobin (69%), diarrhea (64%), nausea (64%), decreased lymphocyte count (63%), fatigue (51%), alopecia (45%), constipation (37%), increased glucose (37%), decreased albumin (35%), vomiting (35%), decreased appetite (30%), decreased creatinine clearance (28%), increased alkaline phosphatase (28%), decreased magnesium (27%), decreased potassium (26%), and decreased sodium (26%). In the ASCENT study (locally advanced or metastatic triple-negative breast cancer), the most common adverse reactions (incidence ≥25%) were fatigue, diarrhea, nausea, alopecia, constipation, vomiting, abdominal pain, and decreased appetite. The most frequent serious adverse reactions (SAR) (>1%) were neutropenia (7%), diarrhea (4%), and pneumonia (3%). SAR were reported in 27% of patients, and 5% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the ASCENT study were reduced neutrophils, leukocytes, and lymphocytes. In the TROPiCS-02 study (locally advanced or metastatic HR-positive, HER2-negative breast cancerHER2-negative breast cancer), the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, nausea, alopecia, and constipation. The most frequent serious adverse reactions (SAR) (>1%) were diarrhea (5%), febrile neutropenia (4%), neutropenia (3%), abdominal pain, colitis, neutropenic colitis, pneumonia, and vomiting (each 2%). SAR were reported in 28% of patients, and 6% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPiCS-02 study were reduced neutrophils and leukocytes. In the TROPHY study (locally advanced or metastatic urothelial cancer), the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, nausea, any infection, alopecia, decreased appetite, constipation, vomiting, rash, and abdominal pain. The most frequent serious adverse reactions (SAR) (≥5%) were infection (18%), neutropenia (12%, including febrile neutropenia in 10%), acute kidney injury (6%), urinary tract infection (6%), and sepsis or bacteremia (5%). SAR were reported in 44% of patients, and 10% discontinued due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPHY study were reduced neutrophils, leukocytes, and lymphocytes. UGT1A1 Inhibitors: Concomitant administration of Trodelvy with inhibitors of UGT1A1 may increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38. Avoid administering UGT1A1 inhibitors with Trodelvy. UGT1A1 Inducers: Exposure to SN-38 may be reduced in patients concomitantly receiving UGT1A1 enzyme inducers. Avoid administering UGT1A1 inducers with Trodelvy. Please see full Prescribing Information, including BOXED WARNING.
Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19, and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California. i ESMO Metastatic Breast Cancer Living Guideline. Available at: https://www.esmo.org/living-guidelines/esmo-metastatic-breast-cancer-living-guideline/er-positive-her2-negative-breast-cancer ; Last accessed: June 2023 ii Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer Version 4.2023. © National Comprehensive Cancer Network, Inc.Cancer Network, Inc. 2023. All rights reserved. Accessed June 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.