162MO - Neoadjuvant chemotherapy and immunotherapy in Luminal B BC: Results of the phase II GIADA trial

Background

The role of immunotherapy in HR+/HER2- breast cancer is underexplored. The GIADA trial (EUDRACT 2016-004665-10) is a phase II study of neoadjuvant chemotherapy, nivolumab and endocrine therapy for Luminal B breast cancer patients.

Methods

Premenopausal patients with Luminal B breast cancer (HR+/HER2- and G3 or Ki67>20%) candidate to neoadjuvant chemotherapy received: 3 cycles of epirubicin/cyclophosphamide Q3W followed by 8 cycles of nivolumab 240 mg Q2W, triptorelin started concomitantly to chemotherapy and exemestane started concomitantly to nivolumab. To reject the null hypothesis, at least 8/43 pCR (ypT0/is and ypN0) had to be observed. Secondary endpoints included safety and biomarkers.

Results

43 patients were included: median age 45y, clinical stage II (81%) and IIIA (19%). All patients started treatment and underwent surgery, 42 received >1 nivolumab dose. A pCR was achieved by 7 patients (16.3%; 95%CI 7.4-34.9). Most common Grade >3 treatment-related AEs during nivolumab were: GGT (18.6%), ALT (16.3%) and AST (9.3%) increase. Most common immune-related AEs were: hyperthyroidism (18.6%), hypothyroidism (14.0%), skin AEs (11.6%), infusion reactions (4.7%), all Grade 1-2 except a Grade 3 skin AE (erythema nodosus). FFPE tumor samples collected at baseline (t0) and after chemotherapy before nivolumab (t1) were assessed by multiplex immunofluorescence for 18 patients (including 4 patients with pCR). At t0 and t1 pCR vs. non-pCR patients had higher CD3+/PD-1+ (p=0.010, p=0.001), CD4+/FOXP3+ (p=0.025, p=0.004) and CD68+/CD163+ (p=0.015, p=0.026) cells. CD8+ cells increased in pCR patients from t0 to t1 (p=0.001 for pCR vs. non-pCR at t1).

Conclusions

A neoadjuvant sequence of anthracycline chemotherapy and nivolumab (+ endocrine therapy) induced a 16.3% pCR rate in Luminal B breast cancer patients (primary endpoint not met). Liver toxicity accounted for most Grade >3 treatment-related AEs. Baseline and on-treatment characterization of immune infiltrate may identify patients more likely to respond. Residual cancer burden and updated biomaker data will be presented.

Clinical trial identification

EUDRACT 2016-004665-10.

Editorial acknowledgement

Legal entity responsible for the study

Department of Surgery, Oncology and Gastroenterology, University of Padova, Padua, Italy.

Funding

Bristol-Myers Squibb (financial support and drug).

Disclosure

M.V. Dieci: Advisory/Consultancy: Genomic Health; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Celgene. V. Guarneri: Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Advisory/Consultancy, Research grant/Funding (institution): Roche. A. Musolino: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Eli Lilly; Advisory/Consultancy: Pfizer; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Eisai; Advisory/Consultancy: Macrogenics; Research grant/Funding (institution): AstraZeneca. S. Spazzapan: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: Gentili; Advisory/Consultancy: Takeda; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Celgene; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Cell-dex therapeutics; Travel/Accommodation/Expenses: Tesaro; Travel/Accommodation/Expenses: Teva. P.F. Conte: Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Honoraria (self), Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Tesaro; Honoraria (self), Research grant/Funding (institution): BMS; Honoraria (self), Research grant/Funding (institution): Roche; Research grant/Funding (institution): Merck-Serono. All other authors have declared no conflicts of interest.