Durvalumab With Olaparib or Cediranib in Women’s Cancers
As reported in the Journal of Clinical Oncology by Lee et al, a phase I study has shown activity of the combination of the programmed cell death ligand 1 (PD-L1) inhibitor durvalumab with either the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib (Lynparza) or vascular endothelial growth factor receptor (VEGFR) 1-3 inhibitor cediranib in recurrent women’s cancers.
Study Details
In the study, durvalumab doublets were assessed in parallel 3 + 3 dose escalations, with durvalumab given intravenously at 10 mg/kg every 2 weeks or 1,500 mg every 4 weeks with either oral olaparib at 200 or 300 mg twice daily or oral cediranib at 20 or 30 mg once daily or 20 mg for 5 days on/2 days off per week. The primary endpoint was the recommended phase II dose.
A total of 26 women were enrolled between June 2015 and May 2016. Of them, 19 had ovarian cancer, 2 had triple-negative breast cancer, 2 had squamous cell cervical cancer, and 3 had uterine cancer.
Recommended Phase II Doses
The recommended phase II doses of the combination regimens were identified as durvalumab at 1,500 mg every 4 weeks plus olaparib at 300 mg twice daily and durvalumab at 1,500 mg every 4 weeks plus cediranib at 20 mg 5 days on/2 days off per week. No dose-limiting toxicity was observed for durvalumab plus olaparib.
The cediranib intermittent schedule was examined in six patients because recurrent grade 2 and non–dose-limiting toxicity grade 3 and 4 adverse events were observed among eight patients receiving the daily schedule; these adverse events included hypertension, diarrhea, and pulmonary embolism in two patients each and pulmonary hypertension and lymphopenia in one patient each. With durvalumab plus intermittent cediranib, grade 3 or 4 adverse events were hypertension and fatigue in one patient each.
Antitumor Activity
Among 12 evaluable patients receiving durvalumab/olaparib, 2 had a partial response (17%; ≥ 15 months and ≥ 11 months) and 8 had stable disease ≥ 4 months (median = 8 months, range = 4–14.5 months), yielding a disease control rate of 83%. Among 12 evaluable patients receiving durvalumab plus cediranib, 6 had a partial response (50%; ≥ 5 to ≥ 8 months) and 3 had stable disease ≥ 4 months (4 to ≥ 8 months), yielding a disease control rate of 75%. Activity was observed independent of PD-L1 expression.
The investigators concluded: “To our knowledge, this is the first reported anti–PD-L1 plus olaparib or cediranib combination therapy. The [recommended phase II doses] of durvalumab plus olaparib and durvalumab plus intermittent cediranib are tolerable and active. Phase II studies with biomarker evaluation are ongoing.”
The study was supported by the National Cancer Institute.
Jung-Min Lee, MD, of the National Cancer Institute, is the corresponding author of the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
