Abstract
Inflammatory breast cancer (IBC) is a highly aggressive entity with a poor outcome and relative resistance to treatment. Despite progresses achieved during the last decades, the survival remains significantly lower than non-IBC. Recent clinical trials assessing PD-1/PD-L1 inhibitors showed promising results in non-IBC. Pembrolizumab, an anti-PD-1 monoclonal antibody, revolutionized the treatment of different cancers. Several recent studies suggested a potential interest of targeting the immune system in IBC by revealing a more frequent PD-L1 expression and an enriched immune microenvironment when compared with non-IBC. Here, we describe the rationale and design of PELICAN-IPC 2015-016/Oncodistinct-003 trial, an open-label, randomized, non-comparative, phase II study assessing efficacy, and safety of pembrolizumab in combination with anthracycline-containing neoadjuvant chemotherapy in HER2-negative IBC. The trial is ongoing. The primary endpoint is the pCR rate (ypT0/Tis, ypN0) in overall population and the co-primary endpoint is safety profile during a run-in phase. Key secondary objectives include tolerability, invasive disease-free, event-free and overall survivals, as well as collection of tumor and blood samples for translational research.Clinical Trial Registration https://clinicaltrials.gov/ (NCT03515798).
Highlights
Inflammatory breast cancer (IBC) is an uncommon and very aggressive form of locally advanced BC
In the World IBC Consortium series including 87 informative IBC samples [50], we identified and validated a robust 107-gene signature associated with pCR and strongly enriched for genes involved in both adaptative and innate immunity
Patients are to be randomly assigned within 28 days from initiation of screening with a 2/1 ratio between neoadjuvant chemotherapy (NACT) without or with pembrolizumab
Summary
Inflammatory breast cancer (IBC) is an uncommon (less than 5% of all BC) and very aggressive form of locally advanced BC. In a cohort of 306 BC samples [51], including 112 IBC samples, PD-L1 was overexpressed in 38% of IBC samples compared to normal breast tissue Such overexpression correlated with aggressive molecular subtypes (TNBC or basal-like and HER2-positive subtypes) and with a higher pCR rate to NACT as well as biological signs of antitumor T-cell cytotoxic response. In a recent study including 143 patients with IBC and 142 control subtypematched patients with non-IBC, PD-L1 IHC expression on immune cells (SP142 antibody) was more frequent in IBC (42.9%) than in non-IBC (23.7%), and correlated with higher pCR rate and stromal TIL infiltration [53] This later was associated with improved overall survival in a multivariate model. In both advanced and early settings, no new signal of toxicity was detected, and tolerance was similar to what expected with ICI in other tumor types
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