# ASCENT: sacituzumab govitecan doubles survival in heavily pretreated metastatic triple-negative breast cancer

Source: https://onco.cc/key-papers/paper-ascent-nejm-2021/  
OnCo record `paper-ascent-nejm-2021` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

In triple-negative breast cancer that had already been through at least two treatments, the TROP2 antibody-drug conjugate sacituzumab govitecan roughly doubled the time patients lived compared with standard chemotherapy.

## Summary

Open-label phase 3 trial of 529 patients with relapsed or refractory metastatic triple-negative breast cancer after two or more prior chemotherapy regimens, randomised to sacituzumab govitecan or single-agent chemotherapy (eribulin, vinorelbine, capecitabine or gemcitabine). The primary endpoint was PFS in the 468 patients without brain metastases.

Median PFS was 5.6 vs 1.7 months (HR 0.41) and median overall survival 12.1 vs 6.7 months (HR 0.48). It converted the 2020 accelerated approval into a full approval and was the first ADC to show a survival benefit in TNBC.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: New England Journal of Medicine
- Year: 2021
- DOI: 10.1056/NEJMoa2028485
- Authors: Bardia A, Hurvitz SA, Tolaney SM, et al.
- Findings: Median PFS 5.6 vs 1.7 months; HR 0.41 (95% CI 0.32-0.52).; Median overall survival 12.1 vs 6.7 months; HR 0.48 (95% CI 0.38-0.59).; Objective response rate 35% vs 5%.; Grade 3 or higher neutropenia 51% vs 33% and diarrhoea 10% vs under 1%; UGT1A1 *28 homozygotes had more neutropenia.; Benefit was seen regardless of TROP2 expression level and in patients with germline BRCA mutations.
- What it means: Sacituzumab govitecan is a standard second-line or later treatment for metastatic triple-negative breast cancer, roughly doubling survival compared with the chemotherapies it was tested against. Patients should expect neutropenia and diarrhoea, which are manageable with growth factor support and loperamide. Trials are now testing it earlier, in first-line combinations with pembrolizumab and after surgery for residual disease.
- Caveats: Open-label; PFS assessed by blinded review.; The control chemotherapies were of modest efficacy in this setting (ORR 5%).; Patients with brain metastases were excluded from the primary analysis and remain under-studied.; The relatively unstable linker releases SN-38 systemically, which contributes to neutropenia and diarrhoea.

## Sources

- NEJM 2021: https://doi.org/10.1056/NEJMoa2028485
- ClinicalTrials.gov NCT02574455: https://clinicaltrials.gov/study/NCT02574455

## Connected records

- ideas: [A randomised trial of antibody-drug conjugate sequence in metastatic triple-negative breast cancer](https://onco.cc/ideas/idea-tnbc-adc-sequencing-trial/), [ADC for residual disease after KEYNOTE-522](https://onco.cc/ideas/idea-post-neoadjuvant-adc/), [Neoadjuvant ADC + IO replacing anthracycline chemotherapy in TNBC](https://onco.cc/ideas/idea-neoadjuvant-adc-io/), [TROP2 PET to choose and sequence TROP2 ADCs](https://onco.cc/ideas/idea-trop2-pet-selection/)
- cancers: [Metastatic triple-negative breast cancer](https://onco.cc/cancers/tnbc-metastatic/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [Topoisomerase-I inhibitors (and ADC payloads)](https://onco.cc/technologies/topoisomerase-inhibitors/)
- targets: [TROP2](https://onco.cc/targets/trop2/)
- drugs: [Sacituzumab govitecan](https://onco.cc/drugs/sacituzumab-govitecan/)
- companies: [Gilead Sciences (incl. Kite)](https://onco.cc/companies/gilead/)
- terms: [Accelerated approval](https://onco.cc/terms/accelerated-approval/), [Linker (ADC)](https://onco.cc/terms/linker/), [Objective response rate (ORR)](https://onco.cc/terms/orr/), [Overall survival (OS)](https://onco.cc/terms/os/), [Payload (ADC)](https://onco.cc/terms/payload/), [Progression-free survival (PFS)](https://onco.cc/terms/pfs/)
- trials: [ASCENT](https://onco.cc/trials/ascent/), [ASCENT-03](https://onco.cc/trials/ascent-03/), [ASCENT-04 / KEYNOTE-D19](https://onco.cc/trials/ascent-04/)
- people: [Aditya Bardia](https://onco.cc/people/aditya-bardia/), [Hope S. Rugo](https://onco.cc/people/hope-rugo/), [Javier Cortés](https://onco.cc/people/javier-cortes/), [Martine Piccart](https://onco.cc/people/martine-piccart/), [Sara A. Hurvitz](https://onco.cc/people/sara-hurvitz/), [Sara M. Tolaney](https://onco.cc/people/sara-tolaney/), [Sibylle Loibl](https://onco.cc/people/sibylle-loibl/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- roadmaps: [Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem](https://onco.cc/roadmaps/tnbc-roadmap/)

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