Neoadjuvant Chemotherapy and Immunotherapy in Luminal B-like Breast Cancer: Results of the Phase II GIADA Trial

Abstract

The role of immunotherapy in hormone receptor (HR)-positive, HER2-negative breast cancer (BC) is underexplored. Experimental designThe neoadjuvant phase II GIADA trial (NCT04659551, EUDRACT 2016-004665-10) enrolled stage II-IIIA premenopausal patients with Luminal B (LumB)-like BC (HR-positive/HER2negative, Ki67>20% and/or histologic Grade 3). Patients received: three 21-days cycles of epirubicin/cyclophosphamide followed by eight 14-days cycles of nivolumab, triptorelin started concomitantly to chemotherapy, and exemestane started concomitantly to nivolumab. Primary endpoint was pathological complete response (pCR; ypT0/is, ypN0). ResultsA pCR was achieved by 7/43 patients (16.3%; 95%CI 7.4-34.9), the rate of Residual Cancer Burden class 0-I was 25.6%. pCR rate was significantly higher for patients with PAM50 Basal BC (4/8, 50%) as compared to other subtypes (LumA 9.1%; LumB 8.3%; p=0.017). Tumor infiltrating lymphocytes (TILs), immune-related gene expression signatures, and specific immune cells subpopulations by multiplex immunofluorescence were significantly associated with pCR. A combined score of Basal subtype and TILs had an AUC of 0.95 (95%CI 0.89-1.00) for pCR prediction. According to multiplex immunofluorescence, a switch to a more immune activated tumor microenvironment occurred following exposure to anthracyclines.Most common Grade >3 treatment-related adverse events (AEs) during nivolumab were: γglutamyltransferase (16.7%), alanine aminotransferase (16.7%), and aspartate aminotransferase (9.5%) increase. Most common immune-related AEs were endocrinopathies (all Grade 1-2; including adrenal insufficiency, n=1). ConclusionsLuminal B-like BCs with a Basal molecular subtype and/or a state of immune activation may respond to sequential anthracyclines and anti-PD-1. Our data generate hypotheses that, if validated, could guide immunotherapy development in this context.Research.

Immunogenomic Landscape in Breast Cancer Reveals Immunotherapeutically Relevant Gene Signatures

“…As shown in Figure 5E , the results indicated that the ITBscore is a robust and independent prognostic biomarker for estimating breast cancer patient outcomes (HR: 0.656, 95% CI: 0.591-0.727), and the correlation between the molecular subtype and ITBscore was significant ( Figure 5F ). The basal and Her2 subtypes, which are associated with more favorable prognoses in response to immunotherapy ( 47 ), presented notably higher ITBscores than the other three subtypes (Kruskal−Wallis, p = 7.4 × 10 −15 ).…”

Clinical relevance of the combined analysis of circulating tumor cells and anti-tumor T-cell immunity in metastatic breast cancer patients

“…This is particularly relevant for BC, which has showed an heterogeneous response to immune checkpoint inhibitors, with a better performance in TNBC, and thus highly requires predictive biomarkers of efficacy ( 56 ). Even if our cohort were mainly characterized by luminal subtypes, our analysis could favor the identification of patients eligible for immune checkpoint inhibitors, since recent evidence reported a potential efficacy of neoadjuvant chemotherapy and immunotherapy also in a subgroup of luminal BC ( 57 ). Application of this strategy to a larger prospective cohort of mBC patients (but also to other BC stages or different cancer backgrounds), will validate the predictive and/or prognostic relevance of this promising immune-oncological biomarker.…”

The immune microenvironment of HPV-positive and HPV-negative oropharyngeal squamous cell carcinoma: a multiparametric quantitative and spatial analysis unveils a rationale to target treatment-naïve tumors with immune checkpoint inhibitors

“…mIF staining was performed on primary tumors and lymph node metastases using the Tyramide Signal Amplification (TSA)-based method (Akoya Biosciences), as previously reported [21][22][23][24]. Two panels were employed to characterize the subsets of tumorinfiltrating immune cells (Table 1).…”