Editor’s Note: At the 2026 ESMO Breast Cancer Congress (ESMO BC), Professor Neelima Vidula from Massachusetts General Hospital presented the findings of the randomized phase II ICI-CHEST, TBCRC044 study (Abstract No. 425RO), offering important clinical insights into one of the most challenging settings in advanced breast cancer. The study investigated whether adding the PD-1 inhibitor pembrolizumab to standard carboplatin chemotherapy could improve outcomes in patients with advanced breast cancer accompanied by chest wall disease (CWD), a population known for extremely poor prognosis and limited responsiveness to systemic therapy.The results showed no significant differences between the two treatment arms in terms of 18-week disease control rate (20% vs. 17%) or progression-free survival. These findings suggest that CWD may represent an immunologically “cold” tumor microenvironment in which immune checkpoint inhibition alone is insufficient to overcome treatment resistance. Oncology Frontier invited Professor Neelima Vidula to provide an in-depth interpretation of the study findings and to discuss the clinical implications and future translational research directions arising from what is currently the largest systemic therapy trial conducted in CWD.
Study Overview
Background
Advanced breast cancer (ABC) with chest wall disease (CWD) responds poorly to systemic therapy. Some patients with triple-negative breast cancer (TNBC) have shown responses to immune checkpoint inhibitors (ICIs). This study evaluated the efficacy of pembrolizumab, an ICI, combined with carboplatin in patients with refractory CWD.
Methods
A randomized phase II trial was conducted across seven centers within the Translational Breast Cancer Research Consortium (TBCRC) in patients with unresectable CWD. Eligible patients included those with TNBC, HR+/HER2− disease following at least two prior lines of endocrine therapy, and HER2+ disease after standard treatment.
Patients were randomized in a 2:1 ratio to:
- Arm A: Pembrolizumab 200 mg plus carboplatin AUC 5 every three weeks
- Arm B: Carboplatin AUC 5 every three weeks
Patients with HER2-positive CWD additionally received trastuzumab.
Patients in Arm A received at least six cycles of therapy. Those achieving complete response (CR), partial response (PR), or stable disease (SD) could discontinue carboplatin and continue pembrolizumab maintenance therapy (Arm Ax). Patients in Arm B who experienced disease progression (PD) were allowed to cross over to pembrolizumab with or without carboplatin (Arm Bx).
The primary endpoint was the 18-week disease control rate (DCR), defined as the percentage of patients achieving CR, PR, or SD. The study was statistically powered to detect a 20% difference in DCR between the two groups.
Results
A total of 76 patients were randomized, including 52 in Arm A and 24 in Arm B. Baseline characteristics were generally balanced between the two groups. However, Arm A included a higher proportion of patients previously treated with platinum agents and more patients with distant metastases beyond the chest wall, whereas Arm B included more patients previously exposed to ICIs.
The 18-week DCR was similar between Arm A and Arm B (20% vs. 17%). Progression-free survival (9% vs. 10%), objective response rate (10% vs. 21%), and best chest wall response (55% vs. 50%) were also comparable between the two groups.
In Arm A, 14 patients (27%) received more than six cycles of therapy (range: 6–24 cycles), while 7 patients (29%) in Arm B received more than six cycles (range: 6–18 cycles).
Sixteen patients from Arm B crossed over to Arm Bx after disease progression, with a median treatment duration of 2.5 cycles (range: 1–8 cycles). Among them, four patients (25%) achieved stable disease lasting longer than nine weeks.
Conclusions
In patients with CWD, pembrolizumab plus carboplatin demonstrated a similar 18-week DCR compared with carboplatin alone, suggesting that CWD may represent an immunologically “cold” tumor subtype requiring novel strategies to stimulate antitumor immune responses.
Ongoing analyses of CWD biopsy samples are being conducted to determine whether patients with durable responses exhibit PD-L1-positive or immune-infiltrated tumors compared with other CWD cases.
As the largest systemic therapy trial conducted to date in CWD, this study establishes an important benchmark for chemotherapy response in this difficult-to-treat population and provides a foundation for future research.
Investigator’s Perspective
Professor Neelima Vidula
“My name is Neelima Vidula. I am a breast medical oncologist at Massachusetts General Hospital and an Assistant Professor of Medicine at Harvard Medical School. I also serve as Director of the Comprehensive Breast Cancer Chest Wall Disease Program at Massachusetts General Hospital, Chair of the Breast Program Clinical Trials Committee, and Associate Director of Clinical Research.
Today, I am honored to present at the 2026 ESMO Breast Cancer Congress the results of our study entitled ‘A Randomized Phase II Study of Pembrolizumab Plus Carboplatin vs. Carboplatin Alone in Unresectable Advanced Breast Cancer With Chest Wall Disease (ICI-CHEST, TBCRC 44)’.
Advanced breast cancer with chest wall disease affects approximately 10% to 15% of breast cancer patients. It can manifest as inflammatory breast cancer or lymphangitic breast cancer, often accompanied by skin nodules and ulceration. These patients typically respond poorly to systemic therapy and experience substantial morbidity and poor overall survival.
We know that certain subtypes of breast cancer may respond to immunotherapy. Therefore, we initiated this investigator-sponsored, multicenter, randomized phase II clinical trial enrolling patients with unresectable and progressive chest wall disease across all breast cancer subtypes.
In this study, patients were randomized in a 2:1 ratio. One group (Arm A) received pembrolizumab plus carboplatin for at least six cycles, after which patients with disease control could continue pembrolizumab with or without carboplatin. The second group (Arm B) initially received carboplatin monotherapy, with the option to cross over to pembrolizumab with or without carboplatin upon disease progression. Patients with HER2-positive disease additionally received trastuzumab.
The primary endpoint was the 18-week disease control rate. In both treatment arms, most patients had triple-negative breast cancer, had previously undergone breast and chest wall radiotherapy, and had received multiple prior lines of systemic therapy. Importantly, patients in the pembrolizumab plus carboplatin arm had a higher baseline burden of distant metastatic disease.
Ultimately, we found that the primary endpoint was similar between the two groups, with 18-week disease control rates of 20% in the pembrolizumab-plus-carboplatin arm and 17% in the carboplatin-alone arm. Median progression-free survival was likewise comparable, at 9 weeks versus 10 weeks, respectively.
Regarding durable responses, defined as patients receiving more than six cycles of treatment, 27% of patients in the combination arm and 29% in the monotherapy arm achieved durable benefit. In addition, 16 patients initially treated with carboplatin alone crossed over to pembrolizumab-based therapy after progression. The median treatment duration after crossover was 2.5 cycles, and four patients achieved stable disease lasting longer than nine weeks.
Our findings demonstrate that pembrolizumab plus carboplatin produced a similar 18-week disease control rate compared with carboplatin alone in patients with chest wall disease. However, durable responses were observed in a subset of patients in both groups.
Our next step is to conduct extensive correlative studies analyzing PD-L1 expression and immune infiltration within chest wall biopsy specimens to better understand the contribution of immunotherapy in this setting. We are also evaluating circulating free DNA (cfDNA), PD-L1 expression in tumor biopsies, and circulating tumor cells to explore their relationship with treatment response.
Overall, this study represents the largest clinical trial conducted to date in patients with chest wall disease and establishes baseline chemotherapy response rates for this particularly challenging patient population.”
