A Phase II Study of Neoadjuvant Atezolizumab and Nab-Paclitaxel in Patients With Anthracycline-Resistant Early-Stage Triple-Negative Breast Cancer

Authors

Clinton Yam
Elizabeth A Mittendorf
Haven R Garber
Ryan Sun
Senthil Damodaran
Rashmi K Murthy
David Ramirez
Meghan Karuturi
Rachel M Layman
Nuhad Ibrahim
Gaiane M Rauch
Beatriz E Adrada
Rosalind P Candelaria
Jason B White
Elizabeth Ravenberg
Alyson Clayborn
Qing Qing Ding
W Fraser Symmans
Sabitha Prabhakaran
Alastair M Thompson
Vicente Valero
Debu Tripathy
Lei Huo
Stacy L Moulder
Jennifer K Litton

Publication Date

6-1-2023

Journal

Breast Cancer Research Treatment

DOI

10.1007/s10549-023-06929-9

PMID

37061619

PMCID

PMC12247189

PubMedCentral® Posted Date

7-11-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Purpose: Neoadjuvant anti-PD-(L)1 therapy improves the pathological complete response (pCR) rate in unselected triple-negative breast cancer (TNBC). Given the potential for long-term morbidity from immune-related adverse events (irAEs), optimizing the risk-benefit ratio for these agents in the curative neoadjuvant setting is important. Suboptimal clinical response to initial neoadjuvant therapy (NAT) is associated with low rates of pCR (2-5%) and may define a patient selection strategy for neoadjuvant immune checkpoint blockade. We conducted a single-arm phase II study of atezolizumab and nab-paclitaxel as the second phase of NAT in patients with doxorubicin and cyclophosphamide (AC)-resistant TNBC (NCT02530489).

Methods: Patients with stage I-III, AC-resistant TNBC, defined as disease progression or a < 80% reduction in tumor volume after 4 cycles of AC, were eligible. Patients received atezolizumab (1200 mg IV, Q3weeks × 4) and nab-paclitaxel (100 mg/m2 IV,Q1 week × 12) as the second phase of NAT before undergoing surgery followed by adjuvant atezolizumab (1200 mg IV, Q3 weeks, × 4). A two-stage Gehan-type design was employed to detect an improvement in pCR/residual cancer burden class I (RCB-I) rate from 5 to 20%.

Results: From 2/15/2016 through 1/29/2021, 37 patients with AC-resistant TNBC were enrolled. The pCR/RCB-I rate was 46%. No new safety signals were observed. Seven patients (19%) discontinued atezolizumab due to irAEs.

Conclusion: This study met its primary endpoint, demonstrating a promising signal of activity in this high-risk population (pCR/RCB-I = 46% vs 5% in historical controls), suggesting that a response-adapted approach to the utilization of neoadjuvant immunotherapy should be considered for further evaluation in a randomized clinical trial.

Keywords

Humans, Female, Anthracyclines, Triple Negative Breast Neoplasms, Neoadjuvant Therapy, Breast Neoplasms, Paclitaxel, Antineoplastic Combined Chemotherapy Protocols, Triple-Negative Breast Cancer, Atezolizumab, Chemotherapy Resistance, Phase II Trial

Published Open-Access

yes

Recommended Citation

Yam, Clinton; Mittendorf, Elizabeth A; Garber, Haven R; et al., "A Phase II Study of Neoadjuvant Atezolizumab and Nab-Paclitaxel in Patients With Anthracycline-Resistant Early-Stage Triple-Negative Breast Cancer" (2023). Faculty, Staff and Student Publications. 4638.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4638