Abstract P1-16-08: Response to subsequent therapy after dual immune checkpoint blockade in metastatic breast cancer
Authors: Shah AN , Yalamanchili A , Helenowski I , Bhole S , Woodman J , Gradishar WJ , Cristofanilli M , Santa-Maria CA 
Published: May 2019

Abstract
Introduction: While initial studies have found that combining chemotherapy with immune checkpoint blockade (ICB) can augment responses, additional toxicity has been observed. The optimal sequencing of chemotherapy and ICB has not yet been described. Sequential responses to chemotherapy after ICB have been reported in various tumor types; however, data is limited, and this has not been described in breast cancer to date.
Methods: We identified patients (pts) from a small pilot study in HER2-negative metastatic breast cancer (MBC) who received at least 1 cycle of durvalumab (PD-L1 inhibitor) and tremelimumab (CTLA-4 inhibitor). We excluded pts without follow up data or if they did not receive subsequent systemic therapy. Comparison of differences between subgroups was calculated by Fisher's exact test for categorical variables and Wilcoxon rank-sum test for continuous variables. Time to treatment failure (TTF) of subsequent therapy and overall survival (OS) were assessed by the Kaplan-Meier method and differences between breast cancer subtype were compared by log-rank tests.
Results: Twenty-three pts received at least 1 cycle of ICB of whom 14 pts were eligible for this analysis. Nine had estrogen receptor positive (ER+) BC and 5 had triple negative (TN) BC. There were no statistically significant differences between the ER+ and TN subgroups in age, race, ethnicity, ECOG performance status (PS) at end of ICB, or sites of metastatic disease except for more lymph node metastases in the TN cohort (p=0.003). Overall response rates to ICB in this cohort was higher in TN vs ER+ (40% vs 0%, p=0.11). Pts received a median of 4 lines of systemic therapy for MBC prior to ICB. Subsequent therapy after ICB was eribulin in 29%, carboplatin/gemcitabine in 21%, palbociclib + endocrine therapy (ET) in 14%, anthracycline in 14%, ixabepilone +/- capecitabine in 14%, and paclitaxel in 7%. Clinical response was seen in 8 pts (57%), of whom 5 had ER+ BC and 3 had TNBC. The median TTF of subsequent therapy was 3.0 mo (1.9, 5.5), which compared to a median TTF for therapy prior to ICB of 2.5 mo. The median OS was 12.3 mo (2.3-13.3). There were no significant differences between the ER+ and TN cohorts (log-rank test p=0.74 and 0.90 for TTF and OS, respectively. Subsequent therapy was discontinued due to progressive disease in 44%, decline in PS in 19%, liver failure in 6%, treatment related adverse event in 6%, and unknown cause in 13%. Two pts remain on subsequent therapy with palbociclib + ET beyond 6 mo without disease progression. There were no statistically significant differences between TTF &gt;3 mo (n=5) and TTF &lt;3 mo (n=9) subgroups. Pts with TTF &gt;3 mo were numerically more likely to have a PS 0-1 (100 vs 78%), liver metastases (80 vs 56%), and ER+ BC (80 vs 56%). Pts with TTF &lt;3 mo had more lymphopenia (66% vs 20%) and more lines of prior systemic therapy for MBC (median 6 vs 4).
Conclusions: While median duration of response on subsequent therapy was short, a subset of pts had significant clinical responses. These findings provide rationale for prospective validation as they provide strategies for sequencing ICB with standard therapies.
Citation Format: Shah AN, Yalamanchili A, Helenowski I, Bhole S, Woodman J, Gradishar WJ, Cristofanilli M, Santa-Maria CA. Response to subsequent therapy after dual immune checkpoint blockade in metastatic breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-16-08.