Abstract 5368
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.
Resources from the same session
4543 - Long-term real-world (RW) outcomes in patients with advanced melanoma (MEL) treated with ipilimumab (IPI) and non-IPI therapies: IMAGE study
Presenter: Stéphane Dalle
Session: Poster Display session 3
Resources:
Abstract
4523 - Prognostic Factors for efficacy of Ipilimumab used after AntiPD1 and/or BRAF+MEK inhibitors in Melanoma Patients: an Italian Melanoma Intergroup study
Presenter: Riccardo Marconcini
Session: Poster Display session 3
Resources:
Abstract
3632 - Rechallenge with combination ipilimumab and anti-PD-1 (IPI+PD1) in metastatic melanoma after acquired resistance to IPI+PD1 immunotherapy
Presenter: Adriana Hepner
Session: Poster Display session 3
Resources:
Abstract
3732 - Clinicopathologic characteristics of immune colitis in melanoma patients treated with combination ipilimumab and anti-PD1 (IPI+PD1) and PD1 monotherapy.
Presenter: Kazi Nahar
Session: Poster Display session 3
Resources:
Abstract
5005 - Real-world outcomes of ipilimumab plus nivolumab for advanced melanoma in the Netherlands
Presenter: Michiel van Zeijl
Session: Poster Display session 3
Resources:
Abstract
5524 - Utilization of Real-World Data to Assess the Effectiveness of Immune Checkpoint Inhibitors (ICIs) in Elderly Patients with Metastatic Melanoma
Presenter: D Scott Ernst
Session: Poster Display session 3
Resources:
Abstract
5884 - Tumor mutational burden and response to PD-1 inhibitors: an analysis of 89 cases of metastatic melanoma.
Presenter: Léa Dousset
Session: Poster Display session 3
Resources:
Abstract
3120 - Increase in S100B and LDH as early outcome predictors for non-responsiveness to anti-PD-1 monotherapy in advanced melanoma.
Presenter: Elisa Rozeman
Session: Poster Display session 3
Resources:
Abstract
2157 - Immune status defined by molecular information layers predicts response to pembrolizumab treatment in advanced melanoma
Presenter: Guillermo Prado-Vázquez
Session: Poster Display session 3
Resources:
Abstract
2553 - Interim analysis of a phase Ib study of cobimetinib plus atezolizumab in patients with advanced BRAFV600 wild type melanoma progressing on prior anti-PD-L1 therapy
Presenter: Shahneen Sandhu
Session: Poster Display session 3
Resources:
Abstract