Immune-related adverse events are associated with better event-free survival in a phase I/II clinical trial of durvalumab concomitant with neoadjuvant chemotherapy in early-stage triple-negative breast cancer

IF 7.1 2区医学 Q1 ONCOLOGY

ESMO Open Pub Date : 2025-03-18 DOI:10.1016/j.esmoop.2025.104494

A. Rios-Hoyo , J. Dai , T. Noel , K.R.M. Blenman , T. Park , L. Pusztai

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Abstract

Background

Immune-related adverse events (irAEs) have been associated with improved outcomes in different tumors; however, their impact during neoadjuvant immune checkpoint inhibitor therapy and chemotherapy in triple-negative breast cancer (TNBC) remains unknown.

Patients and methods

This analysis included patients from a phase I/II single-arm clinical trial at Yale Cancer Center and its regional care centers. The study was conducted from December 2015 to December 2020. Eligible patients were adults aged ≥18 years with clinical stage I-III TNBC for whom systemic chemotherapy was indicated. Patients received durvalumab concomitant with nab-paclitaxel and dose-dense doxorubicin–cyclophosphamide. Durvalumab was not administered post-operatively. We examined the association of developing an irAE with pathologic complete response (pCR = ypT0/is, ypN0), residual cancer burden (RCB), event-free survival (EFS), and overall survival (OS). A landmark analysis from the time of surgery was also carried out.

Results

A total of 67 patients were eligible for toxicity and efficacy analysis; of these, 27 had irAEs of any grade and 13 had multiple irAEs. The median follow-up was 61 months (range 6.8-94.03 months). The most frequent irAEs were dermatologic (n = 14), endocrine (n = 13), and gastrointestinal (n = 5). Patients who experienced irAEs achieved a pCR or RCB 0-1 rate of 56% and 73%, respectively, compared with 40% and 55% in those without irAEs (P = 0.309 and 0.19). Development of irAE was also associated with significantly improved EFS [hazard ratio (HR) 0.25; 95% confidence interval (CI) 0.09-0.66, P = 0.024] and a trend for improved OS (HR 0.42; 95% CI 0.14-1.27, P = 0.17). Patients with more than one irAE had no EFS events. The landmark analysis showed similar results (EFS HR 0.19, P = 0.014; OS HR 0.4, P = 0.16).

Conclusions

The development of irAE was associated with numerically improved pCR rates, lower RCB, and significantly higher EFS in patients treated with neoadjuvant immune checkpoint therapy plus chemotherapy.

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来源期刊

ESMO Open Medicine-Oncology

CiteScore

11.70

自引率

2.70%

发文量

255

审稿时长

10 weeks

期刊介绍： ESMO Open is the online-only, open access journal of the European Society for Medical Oncology (ESMO). It is a peer-reviewed publication dedicated to sharing high-quality medical research and educational materials from various fields of oncology. The journal specifically focuses on showcasing innovative clinical and translational cancer research. ESMO Open aims to publish a wide range of research articles covering all aspects of oncology, including experimental studies, translational research, diagnostic advancements, and therapeutic approaches. The content of the journal includes original research articles, insightful reviews, thought-provoking editorials, and correspondence. Moreover, the journal warmly welcomes the submission of phase I trials and meta-analyses. It also showcases reviews from significant ESMO conferences and meetings, as well as publishes important position statements on behalf of ESMO. Overall, ESMO Open offers a platform for scientists, clinicians, and researchers in the field of oncology to share their valuable insights and contribute to advancing the understanding and treatment of cancer. The journal serves as a source of up-to-date information and fosters collaboration within the oncology community.