Skip to main content
Top
Published in: memo - Magazine of European Medical Oncology 3/2021

01-09-2021 | Breast Cancer | short review

SABCS 2020: update on triple-negative and metastatic HER2-positive breast cancer

Author: Rupert Bartsch

Published in: memo - Magazine of European Medical Oncology | Issue 3/2021

Login to get access

Summary

One year into the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic, the 2020 San Antonio Breast Cancer Symposium (SABCS) was another large congress held in a virtual format. Despite these circumstances, clinically relevant data were presented, and this short review focuses on developments in the fields of triple-negative breast cancer (TNBC) and metastatic HER2-positive breast cancer. A quality-of-life (QoL) analysis from IMPassion031 showed that adding atezolizumab to neoadjuvant chemotherapy was not associated with a detrimental effect on QoL, while the burden of treatment-induced side effects increased with each cycle of neoadjuvant therapy in both treatment arms. KEYNOTE-355 evaluated the addition of pembrolizumab to chemotherapy as first-line treatment in metastatic TNBC (mTNBC); a significant improvement of progression-free survival (PFS) was reported in the pembrolizumab arm. At the 2020 SABCS, results with respect to different chemotherapy backbones were reported and the benefit of pembrolizumab was maintained irrespective of the type of taxane. Disappointingly, the phase III IPATunity130 study could not confirm a PFS improvement with the AKT inhibitor ipatasertib when added to paclitaxel as first-line treatment in mTNBC. A biomarker analysis from the phase III ASCENT study showed that the antibody–drug conjugate sacituzumab govitecan was superior to chemotherapy by investigator’s choice independent of Trop‑2 expression and BRCA mutation status. In HER2-positive breast cancer, the PRECIOUS trial suggested a small albeit significant benefit with reinduction of pertuzumab in later treatment lines in patients progressing on prior dual HER2-blockade in the first- or second-line setting. The HER2-specific tyrosine kinase inhibitor tucatinib when added to trastuzumab and capecitabine was shown to improve PFS and overall survival (OS) over trastuzumab and capecitabine alone in pretreated patients in the randomized HER2CLIMB trial; this benefit was apparently independent of hormone-receptor expression. An update from the DESTINY-Breast01 trial reported a median PFS of 19.4 months with trastuzumab deruxtecan in heavily pretreated patients. Finally, an analysis from the PERTAIN trial with > 6 years median follow-up showed excellent OS in patients with luminal B/HER2-positive receiving first-line trastuzumab/pertuzumab in combination with endocrine therapy suggesting that chemotherapy-free treatment is an option in highly selected patients.
Literature
1.
go back to reference Mittendorf EA, Zhang H, Barrios CH, et al. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet. 2020;396(10257):1090–100.CrossRef Mittendorf EA, Zhang H, Barrios CH, et al. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet. 2020;396(10257):1090–100.CrossRef
2.
go back to reference Mittendorf EA, Harbeck N, Zhang H, et al. Patient-reported outcomes (PROs) from the Ph 3 IMpassion031 trial of neoadjuvant (NA) atezolizumab + chemo in early triple-negative breast cancer (eTNBC). GS3-02. SABCS. 2020. Mittendorf EA, Harbeck N, Zhang H, et al. Patient-reported outcomes (PROs) from the Ph 3 IMpassion031 trial of neoadjuvant (NA) atezolizumab + chemo in early triple-negative breast cancer (eTNBC). GS3-02. SABCS. 2020.
3.
go back to reference Schmid P, Adams S, Rugo HS, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018;379(22):2108–21.CrossRef Schmid P, Adams S, Rugo HS, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018;379(22):2108–21.CrossRef
4.
go back to reference Miles DW, Gligorov J, André F, et al. Primary results from IMpassion131, a double-blind placebo-controlled randomised phase III trial of first-line paclitaxel (PAC) ± atezolizumab (atezo) for unresectable locally advanced/metastatic triple-negative breast cancer (mTNBC). Ann Oncol. 2020;31(Suppl 4):LBA15. Miles DW, Gligorov J, André F, et al. Primary results from IMpassion131, a double-blind placebo-controlled randomised phase III trial of first-line paclitaxel (PAC) ± atezolizumab (atezo) for unresectable locally advanced/metastatic triple-negative breast cancer (mTNBC). Ann Oncol. 2020;31(Suppl 4):LBA15.
5.
go back to reference Cortes J, Cescon DW, Rugo HS, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396(10265):1817–28.CrossRef Cortes J, Cescon DW, Rugo HS, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396(10265):1817–28.CrossRef
6.
go back to reference Rugo H, Schmid P, Cescon DW, et al. Additional efficacy endpoints from the phase 3 KEYNOTE-355 study of pembrolizumab plus chemotherapy vs placebo plus chemotherapy as first-line therapy for locally recurrent inoperable or metastatic triple-negative breast cancer. GS3-01. SABCS. 2020. Rugo H, Schmid P, Cescon DW, et al. Additional efficacy endpoints from the phase 3 KEYNOTE-355 study of pembrolizumab plus chemotherapy vs placebo plus chemotherapy as first-line therapy for locally recurrent inoperable or metastatic triple-negative breast cancer. GS3-01. SABCS. 2020.
7.
go back to reference Kim SB, Dent R, Im SA, et al. Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2017;18(10):1360–72.CrossRef Kim SB, Dent R, Im SA, et al. Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2017;18(10):1360–72.CrossRef
8.
go back to reference Dent R, Kim SB, Mafalda O, et al. Double-blind placebo (PBO)-controlled randomized phase III trial evaluating first-line ipatasertib (IPAT) combined with paclitaxel (PAC) for PIK3CA/AKT1/PTEN-altered locally advanced unresectable or metastatic triple-negative breast cancer (aTNBC). GS3-04. SABCS. 2020. Primary results from IPATunity130 Cohort A. Dent R, Kim SB, Mafalda O, et al. Double-blind placebo (PBO)-controlled randomized phase III trial evaluating first-line ipatasertib (IPAT) combined with paclitaxel (PAC) for PIK3CA/AKT1/PTEN-altered locally advanced unresectable or metastatic triple-negative breast cancer (aTNBC). GS3-04. SABCS. 2020. Primary results from IPATunity130 Cohort A.
9.
go back to reference Bardia A, Tolaney SM, Loirat D, et al. ASCENT: a randomized phase III study of sacituzumab govitecan (SG) vs treatment of physician’s choice (TPC) in patients (pts) with previously treated metastatic triple-negative breast cancer (mTNBC). Ann Oncol. 2020;31(Suppl 4):LBA17. Bardia A, Tolaney SM, Loirat D, et al. ASCENT: a randomized phase III study of sacituzumab govitecan (SG) vs treatment of physician’s choice (TPC) in patients (pts) with previously treated metastatic triple-negative breast cancer (mTNBC). Ann Oncol. 2020;31(Suppl 4):LBA17.
10.
go back to reference Hurvitz SA, Tolaney SM, Punie K, et al. Biomarker evaluation in the phase 3 ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer. GS3-06. SABCS. 2020. Hurvitz SA, Tolaney SM, Punie K, et al. Biomarker evaluation in the phase 3 ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer. GS3-06. SABCS. 2020.
11.
go back to reference Diéras V, Weaver R, Tolaney SM, et al. Subgroup analysis of patients with brain metastases from the phase 3 ASCENT study of sacituzumab govitecan versus chemotherapy in metastatic triple-negative breast cancer. PD13-07. SABCS. 2020. Diéras V, Weaver R, Tolaney SM, et al. Subgroup analysis of patients with brain metastases from the phase 3 ASCENT study of sacituzumab govitecan versus chemotherapy in metastatic triple-negative breast cancer. PD13-07. SABCS. 2020.
12.
go back to reference Brenner AJ, Pandey R, Chiou J, et al. Delivery and activity of SN-38 by sacituzumab govitecan in breast cancer brain metastases. PD13-05. SABCS. 2020. Brenner AJ, Pandey R, Chiou J, et al. Delivery and activity of SN-38 by sacituzumab govitecan in breast cancer brain metastases. PD13-05. SABCS. 2020.
13.
go back to reference Yamamoto Y, Iwata H, Naruto T, et al. A randomized, open-label, phase III trial of pertuzumab re-treatment in HER2-positive, locally advanced/metastatic breast cancer patients previously treated with pertuzumab, trastuzumab, and chemotherapy. PD3-11. SABCS. 2020. The Japan Breast Cancer Research Group-M05 (PRECIOUS) study. Yamamoto Y, Iwata H, Naruto T, et al. A randomized, open-label, phase III trial of pertuzumab re-treatment in HER2-positive, locally advanced/metastatic breast cancer patients previously treated with pertuzumab, trastuzumab, and chemotherapy. PD3-11. SABCS. 2020. The Japan Breast Cancer Research Group-M05 (PRECIOUS) study.
14.
go back to reference Murthy RK, Loi S, Okines A, et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med. 2020;382(7):597–609.CrossRef Murthy RK, Loi S, Okines A, et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med. 2020;382(7):597–609.CrossRef
15.
go back to reference Lin NU, Borges V, Anders C, et al. Intracranial efficacy and survival with tucatinib plus trastuzumab and capecitabine for previously treated HER2-positive breast cancer with brain metastases in the HER2CLIMB trial. J Clin Oncol. 2020;38(23):2610–9.CrossRef Lin NU, Borges V, Anders C, et al. Intracranial efficacy and survival with tucatinib plus trastuzumab and capecitabine for previously treated HER2-positive breast cancer with brain metastases in the HER2CLIMB trial. J Clin Oncol. 2020;38(23):2610–9.CrossRef
16.
go back to reference Hamilton E, Reinisch M, Loi S, et al. Tucatinib vs placebo in combination with trastuzumab and capecitabine for patients with locally advanced unresectable or HER2-positive metastatic breast cancer (HER2CLIMB): Outcomes by hormone receptor status. PD3-08. SABCS. 2020. Hamilton E, Reinisch M, Loi S, et al. Tucatinib vs placebo in combination with trastuzumab and capecitabine for patients with locally advanced unresectable or HER2-positive metastatic breast cancer (HER2CLIMB): Outcomes by hormone receptor status. PD3-08. SABCS. 2020.
17.
go back to reference Modi S, Saura C, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med. 2020;382(7):610–21.CrossRef Modi S, Saura C, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med. 2020;382(7):610–21.CrossRef
18.
go back to reference Modi S, Saura C, Xamashita T, et al. Updated results from DESTINY-breast01, a phase 2 trial of trastuzumab deruxtecan (T-DXd ) in HER2 positive metastatic breast cancer. PD3-06. SABCS. 2020. Modi S, Saura C, Xamashita T, et al. Updated results from DESTINY-breast01, a phase 2 trial of trastuzumab deruxtecan (T-DXd ) in HER2 positive metastatic breast cancer. PD3-06. SABCS. 2020.
19.
go back to reference Rimawi M, Ferrero JM, de la Haba-Rodriguez J, et al. First-line trastuzumab plus an aromatase inhibitor, with or without pertuzumab, in human epidermal growth factor receptor 2‑positive and hormone receptor-positive metastatic or locally advanced breast cancer (PERTAIN): a randomized, open-label phase II trial. J Clin Oncol. 2018;36(28):2826–35.CrossRef Rimawi M, Ferrero JM, de la Haba-Rodriguez J, et al. First-line trastuzumab plus an aromatase inhibitor, with or without pertuzumab, in human epidermal growth factor receptor 2‑positive and hormone receptor-positive metastatic or locally advanced breast cancer (PERTAIN): a randomized, open-label phase II trial. J Clin Oncol. 2018;36(28):2826–35.CrossRef
20.
go back to reference Arpino G, de la Haba-Rodriguez J, Ferrero JM, et al. Final analysis of PERTAIN. PD3-02. SABCS. 2020. A randomized, two-arm, open-label, multicenter phase II trial assessing the efficacy and safety of first-line pertuzumab given in combination with trastuzumab plus an aromatase inhibitor in patients with HER2-positive and hormone receptor-positive metastatic or locally advanced breast cancer. Arpino G, de la Haba-Rodriguez J, Ferrero JM, et al. Final analysis of PERTAIN. PD3-02. SABCS. 2020. A randomized, two-arm, open-label, multicenter phase II trial assessing the efficacy and safety of first-line pertuzumab given in combination with trastuzumab plus an aromatase inhibitor in patients with HER2-positive and hormone receptor-positive metastatic or locally advanced breast cancer.
Metadata
Title
SABCS 2020: update on triple-negative and metastatic HER2-positive breast cancer
Author
Rupert Bartsch
Publication date
01-09-2021
Publisher
Springer Vienna
Published in
memo - Magazine of European Medical Oncology / Issue 3/2021
Print ISSN: 1865-5041
Electronic ISSN: 1865-5076
DOI
https://doi.org/10.1007/s12254-021-00722-4

Other articles of this Issue 3/2021

memo - Magazine of European Medical Oncology 3/2021 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine