5368 - Durvalumab and Paclitaxel Combination for treatment of metastatic triple negative breast cancer is safe with very promising efficacy

Background

Immunotherapy with anti PD-1/PD-L1 antibodies as a monotherapy showed promising results with limited success in triple negative breast cancer. As the combination of paclitaxel and anti PD-L1 was likely synergistic, our aim was to test safety, toxicities, tolerability and efficacy of this combination.

Methods

We have initiated an open label, interventional phase I/II clinical trial to test the safety and efficacy of a combination of Durvalumab (therapeutic anti-PD-L1 antibody) and paclitaxel for the treatment of metastatic triple negative breast cancer (TNBC). After 1 cycle of weekly paclitaxel alone, Durvalumab was given every two weeks in combination with paclitaxel that was delivered on days 1, 8 and 15 of each 28 days’ cycle.

Results

Between 2017-2019, we enrolled 19 patients (25-61 years old) of which 14 were treated with the combination therapy, while the remaining 5 dropped out due to tumor progression (n = 3) or intolerance to first cycle of paclitaxel alone (n = 2). Patients had metastatic infiltrating ductal carcinoma with two patients having a metaplastic pathological subtype. No dose limiting toxicity was reported. Patients who received combination therapy are still alive except two dead due to progression of disease. The most common adverse effects, regardless of grade, were: anemia 25%, neutropenia, and leukopenia (20% each). In addition, neuropathy, and dyspnea were seen in 15% of patients (each). Grade 3/4 adverse effects were anemia, neutropenia, leukocytopenia, headache, fatigue and abdominal pain. There was one case of colitis (grade 2). Among evaluable combination treated patients (n = 12), 5 patients (42%) initially showed objective response with a median duration of 7.1 months, while the disease control rate was 67%. However, 6 (55%) showed signs of progression later on leaving only 1 patient with CR, and another with SD. So far there is a definite increase in survival of TNBC with the combination therapy compared to historical rates of paclitaxel alone. However, the end point has not been reached yet.

Conclusions

Combination of Durvalumab and Paclitaxel is safe with very promising efficacy in metastatic TNBC.

Clinical trial identification

NCT02628132.

Editorial acknowledgement

Legal entity responsible for the study

Hazem Ghebeh PhD and Taher Twegieri MD.

Funding

AstraZeneca (ESR-14-10649) and KFSH&RC (RAC# 2151-169).

Disclosure

All authors have declared no conflicts of interest.