Durvalumab plus olaparib or intermittent cediranib is clinically active and tolerable in treating female cancers, according to results from a phase 1 study published in the Journal of Clinical Oncology.1
Olaparib is a PARP inhibitor and cediranib is a VEGFR 1-3 inhibitor.
“We hypothesized that increased DNA damage by PARP inhibitor and/or reduced VEGF signaling by the VEGFR inhibitor may complement the antitumor activity of immune checkpoint inhibition,” wrote the authors.
This dose-escalation, phase 1 study evaluated the pharmacokinetics, antitumor activity, and safety of durvalumab plus olaparib or cediranib.
The study treated 26 women with recurrent or metastatic solid malignancies who had not received prior immune checkpoint inhibitor therapy. Cancer types included ovarian, triple-negative breast, cervical, and uterine.
All patients received durvalumab 10 mg/kg every 2 weeks or 1500 mg every 4 weeks. Olaparib was administered as 200 or 300 mg twice daily and cediranib was administered as 20 or 30 mg once daily or 20 mg for 5 days then 2 days off.
The recommended phase 2 dosing was 1500 mg every 4 weeks of durvalumab plus 300 mg twice daily of olaparib or 20 mg of intermittent cediranib. There were no dose-limiting toxicities associated with durvalumab plus olaparib.
Treatment-emergent adverse events were hypertension, diarrhea, pulmonary embolism, pulmonary hypertension, and lymphopenia.
Durvalumab plus olaparib resulted in an objective response rate (ORR) of 17% and a disease control rate of 83%. There were 2 partial responses that lasted at least 11 months and 8 patients achieved stable disease for at least 4 months.
The ORR was 50% and the disease control rate was 75% with durvalumab plus cediranib, with 6 partial responses of at least 5 months and 3 achieved stable disease for at least 4 months.
PD-L1 expression levels did not influence response.
According to the authors, these findings warrant additional studies. Single-arm phase 2 expansion trials are ongoing.
1Lee JM, Cimino-Mathews A, Peer CJ, et al. Safety and clinical activity of the programmed death-ligand 1 inhibitor durvalumab in combination with poly (ADP-ribose) polymerase inhibitor olaparib or vascular endothelial growth factor receptor 1-3 inhibitor cediranib in women’s cancers: a dose-escalation, phase I study. J Clin Oncol. 2017 May 4. doi: 10.1200/JCO.2016.72.1340 [Epub ahead of print]
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