Abstract 435P
Background
PARP inhibitors (PARPis) induce STING-cGAS activation and increase tumor mutational load in TNBC preclinical models, making TNBC sensitive to immune checkpoint blockade. The MEDIOLA phase II study demonstrated a 63.3% overall response rate (ORR) defined as CR+PR with D+O in PARPi naïve gBRCAm BC (1 median number of prior therapies [range 0-4]). We evaluated D+O activity in heavily pretreated TNBC.
Methods
Key eligibility criteria include metastatic TNBC, adequate performance status and organ function. Patients (pts) with prior use of D or PARPi, and active CNS or leptomeningeal disease were not eligible. No limit on the number of prior systemic therapies. For germline BRCA wild type (gBRCAwt), Simon’s 2-stage design with a target of 30% ORR with α=0.1 and β=0.1 was used. If ≥ 2 responses in the first stage (16 pts), 9 additional pts were planned to enroll. 5 ≥ of 25 responses warrant a further later stage study. For gBRCAm, a pilot single stage design was used with a stopping rule. If 1≥ response in the first 5 pts, another 5 pts were planned to enroll. RP2D determined in our earlier phase I study; D 1500 mg iv q4w and O 300 mg BID po (28-day cycle) was administered until PD or intolerable toxicity. The primary endpoint was ORR by RECIST v1.1 (CT q2mo). Secondary objectives were safety by CTCAE v4.03, clinical benefit rate (CBR) defined by CR+PR+SD≥4mo, and PFS.
Results
14 of 15 pts were RECIST evaluable (11 gBRCAwt and 3 gBRCAm). The median number of prior therapies are 3 (range 0-9). A majority of pts (78.6%; 11/14) had ≥ 3 prior systemic therapies and 64.3% (9/14) had previous platinum. Of note, 4 pts had either HR+/HER2-BC (n=3) or HR+/HER2+BC (n=1) at diagnosis which converted to TNBC at recurrence. ORR was 28.5% (3/3 gBRCAm [3 PR] and 1/11 gBRCAwt [PR for 10.3 mo]). One pt with gBRCAm remains on the study with PR >4 yr (96% reduction at best). CBR was 42.9% (3/3 gBRCAm and 3/11 gBRCAwt). Median PFS was 3.7 mo (IQR 1.9-10.3). There were no new safety signals. Accrual is ongoing.
Conclusions
D+O exhibited modest clinical activity in heavily pretreated TNBC pts with or without gBRCAm. Comprehensive biomarker and pharmacodynamic studies are ongoing for the exceptional responder with gBRCAm.
Clinical trial identification
NCT02484404 Release date: June 29, 2015.
Editorial acknowledgement
No editorial assistance
Legal entity responsible for the study
J-M. Lee.
Funding
Intramural Research Program of the NCI, CCR (grant number: #ZIA BC011525; to J-M. Lee) Durvalumab and olaparib were supplied to the CCR, NCI under a Cooperative Research and Development Agreement between the CCR/NCI and AstraZeneca. Research funding was also provided by AstraZeneca to the institution.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
338P - Breast cancer follow-up: A population-based cohort study
Presenter: Serena Di Cosimo
Session: Poster session 03
339P - An online mindfulness-based stress-reduction (MBSR) intervention for breast cancer (BC) survivors: A randomized trial
Presenter: Misael Salazar-Alejo
Session: Poster session 03
340P - Novel application of spatial analyses to investigate environmental factors and hormone receptor-positive breast cancer
Presenter: Alexandra Thomas
Session: Poster session 03
341P - Impact of environmental temperature on clinical outcomes of early-stage breast cancer (BC)
Presenter: Arya Mariam Roy
Session: Poster session 03
342P - Fertility preservation in young breast cancer patients: Patient's knowledge and perception
Presenter: Zeineb Naimi
Session: Poster session 03
343P - Modulation of the immune system (ImS) during moderate physical activity (mPA) in breast cancer (BC) patients (pts) treated with neoadjuvant chemotherapy (NACT)
Presenter: Ornella Garrone
Session: Poster session 03
344P - Epidemiological analysis and overall survival of female breast cancer in a developing middle eastern country over 18 years
Presenter: Mahmoud Abunasser
Session: Poster session 03
345P - The effect of early post-operative exercise on shoulder function in breast cancer patients: A randomised controlled trial
Presenter: Jihee Min
Session: Poster session 03
348P - Long-term opioid use following treatment of localized breast cancer: A real-world analysis
Presenter: Ayelet Shai
Session: Poster session 03