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
5650 - Tissue-based activation of mucosal-associated invariant T (MAIT) cells in combination ipilimumab and nivolumab checkpoint inhibitor (CI) colitis.
Presenter: Sarah Sasson
Session: Poster Display session 3
Resources:
Abstract
5944 - Significance of severe immune-related adverse effects (irAE) on patients with advanced tumors treated with immune checkpoint inhibitors being admitted for secondary toxicity: Clinical relevance and next steps
Presenter: Leyre Zubiri
Session: Poster Display session 3
Resources:
Abstract
5989 - Implementation of a dedicated immuno-oncology toxicity service reduces the acute impact of immune-related adverse events
Presenter: Anna Olsson-Brown
Session: Poster Display session 3
Resources:
Abstract
3267 - Cardiotoxic and pro-inflammatory effects induced by the association of immune checkpoint inhibitor Pembrolizumab and Trastuzumab in preclinical models
Presenter: Nicola Maurea
Session: Poster Display session 3
Resources:
Abstract
3417 - Interstitial lung disease associated with immune-checkpoint inhibitors in malignant diseases
Presenter: Akira Yamagata
Session: Poster Display session 3
Resources:
Abstract
2071 - A Phase 1 Study of Intraperitoneal MCY-M11 Anti-Mesothelin CAR for Women with Platinum Resistant High Grade Serous Adenocarcinoma of the Ovary, Primary Peritoneum, or Fallopian Tube, or Subjects with Peritoneal Mesothelioma with Recurrence after Prior Chemotherapy
Presenter: Christina Annunziata
Session: Poster Display session 3
Resources:
Abstract
4935 - Trial in progress: First-in-human study of a novel anti-NY-ESO-1–anti-CD3, TCR-based bispecific (IMCnyeso) as monotherapy in NY-ESO-1/LAGE-1A-positive advanced solid tumors (IMCnyeso-101)
Presenter: Juanita Lopez
Session: Poster Display session 3
Resources:
Abstract
5613 - Nimotuzumab-Cisplatin-Radiation versus Cisplatin-Radiation in HPV negative oropharyngeal cancer
Presenter: Kumar Prabhash
Session: Poster Display session 3
Resources:
Abstract
2576 - Interim analysis of a single arm phase 2 study of adjuvant nivolumab after salvage resection in head and neck squamous cell carcinoma patients previously treated with definitive therapy.
Presenter: Trisha Wise-draper
Session: Poster Display session 3
Resources:
Abstract
4758 - A Phase I Study of the CDK4/6 Inhibitor, Palbociclib in combination with Cetuximab and Intensity Modulated Radiation Therapy (IMRT) for Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN); A Result of Dose Escalation Cohort
Presenter: Nuttapong Ngamphaiboon
Session: Poster Display session 3
Resources:
Abstract