Developing Story: Triple Negative MBC - Hard Truths, Real Hope with Dr Sarah Premji
Listen to full episode :
Live from Stage 4 | Episode #039| 07/1/2026 | Developing Story
GUESTS
Dr. Sarah Premji, MD, is a board-certified medical oncologist specializing in breast oncology. She serves as the Assistant Director of Breast Cancer Research at the Sarah Cannon Research Institute (SCRI) and practices clinically at SCRI Oncology Partners in Nashville, Tennessee.
🎓 Education & Training
Undergraduate Degree: B.S. in Biology and B.S. in Psychology from the University of Georgia.
Medical Degree: M.D. from the Medical College of Georgia.
Residency: Internal Medicine at the Baylor College of Medicine in Houston, Texas.
Fellowship: Hematology and Oncology at the Mayo Clinic in Rochester, Minnesota.
🏥 Current Roles & Clinical Focus
Research Leadership: Appointed as Assistant Director of Breast Cancer Research in late 2025 to lead operations across SCRI’s clinical trials network.
Clinical Practice: Works as a medical oncologist at SCRI Oncology Partners treating breast cancer patients.
Specialized Expertise: Focuses on biology-driven, personalized oncology care, liquid biopsies (ctDNA), and minimizing treatment toxicity for individual patient needs.
🏆 Awards & Professional Impact
ASCO Award: Recipient of the prestigious 2025 ASCO Conquer Cancer Young Investigator Award.
Board Certifications: Triple board-certified by the American Board of Internal Medicine in Internal Medicine, Hematology, and Medical Oncology.
Industry Contributor: Serves as an expert commentator and presenter at major conferences like the American Society of Clinical Oncology (ASCO).
Quick Summary
In this episode of Live from Stage IV, Victoria Goldberg and Dr. Sarah Premji of the Sarah Cannon Research Institute break down the most complex subtype of metastatic breast cancer: triple negative. They cover what makes TNBC so difficult to treat, how two newly FDA approved antibody drug conjugates are changing the first line standard of care, and what the pipeline ahead looks like for patients navigating this diagnosis. A must listen for anyone in the MBC community.
Key Takeaways
Triple negative breast cancer is not one disease. It is a bucket of different cancers unified only by the absence of ER, PR, and HER2 receptors, making it highly heterogeneous and difficult to treat with a one-size-fits-all approach.
PD-L1 status is the first fork in the road. A combined positive score of 10 or higher determines whether a patient is eligible for immunotherapy alongside their first line treatment. It is the single most important biomarker to know upfront.
The first line standard of care just changed. For the first time, antibody drug conjugates are approved in the first line setting. Trodelvy (sacituzumab govitecan) is now approved for both PD-L1 positive patients (with pembrolizumab) and PD-L1 negative patients (as a standalone). Datroway (datopotamab deruxtecan) received approval specifically for patients not eligible for immunotherapy.
These two drugs are not interchangeable. While both target TROP2, they have meaningfully different side effect profiles, administration schedules, and drug-to-antibody ratios. The choice between them depends heavily on a patient's individual health picture.
Get tested for BRCA, PALB2, and germline mutations early. These results can open the door to PARP inhibitors, which exploit a specific weakness in cancer cells that carry these mutations. Timing of when to use them relative to immunotherapy matters.
Brain metastases are a real concern in TNBC. Triple negative has a higher tendency to spread to the brain. Both major trials allowed patients with treated and stable brain metastases, and researchers are actively working on treatments that can cross the blood-brain barrier.
Crossover in clinical trials can obscure overall survival data. When patients in the control arm are allowed to switch to the study drug after progression, it becomes harder to measure overall survival benefit, even when the drug is genuinely working.
The next generation of treatments is already in trials. New ADCs with dual targets (like Isabrin, targeting EGFR and HER3), different payloads, and entirely new surface targets like B7H4 (being studied in the EMILY trial) are showing early promise for patients who have exhausted current options.
KEYNOTE-522 has reshaped the metastatic landscape. Most patients diagnosed today will have already received immunotherapy and multiple chemotherapy rounds in the early stage setting, which changes which treatments remain available if the cancer returns.
More options than ever, but urgent unmet needs remain. Patients who relapse quickly after KEYNOTE-522 and those who progress after first line ADCs still represent a critical gap. That is where much of the current research is focused.
Clinical Trials Referenced in This Episode
For informational purposes only. Always consult your oncologist before making any treatment decisions.
KEYNOTE-522 (NCT03036488) Stage: Early stage TNBC What it studied: Pembrolizumab (Keytruda) added to chemotherapy before and after surgery Why it matters: Established immunotherapy plus chemo as the new standard of care for early stage TNBC. Most patients entering the metastatic setting today have already been through this regimen.
KEYNOTE-355Stage: Metastatic TNBC, first line What it studied: Pembrolizumab plus chemotherapy for PD-L1 positive tumors (CPS 10 or higher) Why it matters: Set the previous standard of care before antibody drug conjugates entered the first line.
ASCENT-03 Stage: Metastatic TNBC, first line, PD-L1 negative What it studied: Trodelvy (sacituzumab govitecan) vs. chemotherapy Result: Progression-free survival improved from 6.9 to 9.7 months Status: FDA approved June 2026
ASCENT-04Stage: Metastatic TNBC, first line, The primary objective of this study is to compare the progression-free survival (PFS) between sacituzumab govitecan-hziy (SG) and pembrolizumab versus treatment of physician's choice (TPC) and pembrolizumab in participants with previously untreated, locally advanced inoperable or metastatic triple-negative breast cancer, whose tumors express programmed cell death ligand 1 (PD-L1).
TROPION-Breast02 Stage: Metastatic TNBC, first line, patients not eligible for immunotherapy What it studied: Datroway (datopotamab deruxtecan) vs. single agent chemotherapy Result: Progression-free survival improved from 5.6 to 10.8 months Status: FDA approved May 2026
DESTINY-Breast04 Stage: HER2-low tumors including a subset of TNBC What it studied: Enhertu (trastuzumab deruxtecan) in later lines Why it matters: Opened a treatment pathway for the approximately 11% of TNBC patients whose tumors express low levels of HER2
IZABRIGHT-Breast01 Stage: Metastatic TNBC The purpose of this study is to assess the efficacy and safety of iza-bren, a bi-specificantibody-drug conjugate against EGFR and HER3 with a topoisomerase inhibitor payload versus treatment of physician's choice (TPC) (paclitaxel, nab-paclitaxel, carboplatin plus gemcitabine, and capecitabine) for the treatment of first-line metastatic triple-negative breast cancer (TNBC) or estrogen receptor (ER)-low, human epidermal growth factor receptor 2 (HER2)-negative BC patients who are not candidates for anti-PD(L)1 therapy and endocrine therapies.
Emi-le Stage: Metastatic TNBC including treatment-resistant patients Emi-Le (emiltatug ledadotin or XMT-1660) is an investigational antibody-drug conjugate targeting B7-H4 for hard-to-treat cancers like advanced adenoid cystic carcinoma and breast cancer. Developed by Servier, Emi-Le (XMT-1660) is a B7-H4-directed ADC with an auristatin F-HPA microtubule inhibitor payload. it received an FDA Breakthrough Therapy designation in May 2026
Want to learn more? Visit ClinicalTrials.gov to search for open trials by diagnosis, location, and treatment history. Your oncologist can help you determine which trials, if any, may be appropriate for your situation.
Chapter Timestamps
0:00 Introduction and FDA Approval Updates
2:57 Meet Dr. Sarah Premji
3:35 What Is Triple Negative Breast Cancer?
5:13 Biomarkers: PD-L1, HER2-low, BRCA and PALB2 15:25 The ASCENT-03 Trial: Trodelvy in the First Line
17:26 How First Line Treatment Is Changing
29:50 Understanding Antibody Drug Conjugates 46:10 Treatment Sequencing: How Oncologists Decide
57:20 How Oncologists Sequence Treatments
1:02:43 Brain Metastases in Triple Negative MBC
1:08:13 What Is Coming Next in the Pipeline
Listen Next
HER2-Positive Metastatic Breast Cancer with Dr. Premji & Dr. Erika Hamilton (coming soon)
Disclaimer: Everything discussed in this episode is for informational purposes only and does not constitute medical advice. Every patient's situation is unique. Please consult your oncologist and medical team before making any treatment decisions.
