How a New Combo Fights Aggressive Cancer!

How a New Combo Fights Aggressive Cancer. Sacituzumab govitecan (Trodelvy) ADC + Pembrolizumab (Keytruda) immunotherapy improve progression-free survival (PFS) in PD-L1-positive triple-negative breast cancer: ASCENT-04/KEYNOTE-D19 phase 2 clinical trial explained.

Triple-negative breast cancer (TNBC) is aggressive and lacks targeted options. ASCENT-04/KEYNOTE-D19 tested the antibody-drug conjugate sacituzumab govitecan plus checkpoint inhibitor pembrolizumab versus standard chemotherapy + pembrolizumab in previously untreated, PD-L1-positive metastatic TNBC. The combo achieved a median progression-free survival of 11.4 months (vs 5.6 months) and an overall response rate of 63% (vs 35%), with manageable safety—mainly neutropenia and diarrhea—similar to prior Trodelvy data. Mechanistically, Trodelvy delivers the SN-38 payload directly to Trop-2-expressing tumor cells, while Keytruda lifts immune brakes, giving T cells room to attack. Together they extend disease control without adding prohibitive toxicity, positioning this regimen as a potential first-line standard.

Watch for confirmatory phase 3 trials (ASCENT-04 expansion) and biomarker analyses to refine patient selection.

Key points covered in this video• Why TNBC remains hard to treat• Trial design, eligibility & PD-L1 testing• Efficacy data (PFS, ORR, emerging OS)• Safety profile & management pearls• How ADC + immunotherapy work synergistically• Clinical practice implications & unanswered questions

Chapters

00:00 Introduction
00:05 Ascent-04 / Keynote-D19 Trial for TNBC
00:13 Understanding Triple Negative Breast Cancer (TNBC)
00:20 Standard First-Line Treatment for Advanced TNBC
00:39 Ascent-04: Testing a "Smart Chemo" Drug
00:47 Phase 3 Study Design: Comparing Two Regimens
01:10 Sacituzumab Govitecan (Trodelvy): An Antibody-Drug Conjugate
01:28 Pembrolizumab (Keytruda): Immunotherapy Mechanism
01:39 The Combination: A Two-Front Attack on Cancer
02:02 Trial Results: Improved Progression-Free Survival
02:32 Safety Profile and Side Effects
03:04 Clinical Implications and Future of TNBC Treatment

#TripleNegativeBreastCancer #TNBC #CancerTreatment #Immunotherapy #Chemotherapy #Keytruda #Trodelvy #ClinicalTrial #BreastCancer #Ascent04 #SacituzumabGovitecan #Pembrolizumab #PDL1

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ABOUT DR. ESTEVA:Francisco J. Esteva, MD, PhD is a practicing physician located in New York, NY, specializing in Oncology with a focus on breast cancer. His education includes an Oncology Fellowship at Georgetown University Hospital and Internal Medicine Residency at Cooper Medical School of Rowan University. Prior to his current position as Division Chief at Lenox Hill Hospital, Dr. Esteva has held professorship positions at NYU and The University of Texas MD Anderson Cancer Center, as well as serving as VP Clinical Development for Cellectis. In addition to multiple esteemed publications, he has led more than 100 clinical trials related to breast cancer treatments, diagnostics and prognostic/predictive markers. Dr. Esteva was recognized as a Fellow by the American College of Physicians in 2002, elected as a member of The American Society for Clinical Investigation in 2010 and awarded the 2019 Physician of Impact award by the NYC chapter of the Susan G. Komen Foundation. In 2024, he was elected to the NYC American Cancer Society Board of Advisors.

⚠️ The information in this video is not intended nor implied to be a substitute for professional medical advice, diagnosis, or treatment. All content, including text, graphics, images, and information, contained in this video is for general information purposes only and does not replace a consultation with your own doctor/health professional. The views shared in this video represent Dr. Esteva's personal opinions and do not reflect those of his employer.