A Phase 1/2 Study of Chemo-Immunotherapy with Durvalumab and Pegylated Liposomal Doxorubicin (PLD) in Platinum-Resistant Recurrent Ovarian Cancer
Expression of programmed cell death ligand 1 (PD-L1) has been confirmed in human ovarian cancer cells, and preliminary evidence has supported the antitumor activity of anti–PD-1 therapies, like durvalumab, in treating ovarian cancers.1 In a phase 1/2, multicenter, open-label study, O’Cearbhaill and colleagues reported the preliminary safety and efficacy data of treating patients with platinum-resistant recurrent ovarian cancer with durvalumab in combination with standard-of-care pegylated liposomal doxorubicin (PLD).2
This study included a phase 1 3+3 dose escalation, with dose-limiting toxicity evaluated in one 28-day cycle (n = 6-18), and a phase 2 dose-expansion cohort (n = 41). Given that PLD has been reported to have a 6-month progression-free survival (PFS6) of 25%, the sample size of 41 evaluable patients is appropriately powered to test the null hypothesis of a PFS6 rate of ≤25% against the alternative hypothesis of a PFS rate of ≥45% at an alpha level of 0.05 (one-sided). Blood and tumor samples were also collected for assessment of correlative immunologic responses.
As of March 5, 2018, 40 female patients with a median age of 65 years (range, 32-83 years) were enrolled in phase 2 of the study. Each had received at least 1 dose of study therapy (PLD 40 mg/m2 + durvalumab 1500 mg once every 4 weeks) and were included in the safety analyses. The most frequently observed treatment-emergent adverse events (AEs, all causality), occurring in ≥25% of patients, were palmar-plantar erythrodysesthesia syndrome (PPES)/rash, stomatitis, fatigue, abdominal pain, nausea, pyrexia, and vomiting. Grade 3 treatment-related AEs in ≥2 patients included PPES/rash, stomatitis, lymphocyte count decreased, lipase increased, and anemia. As of the cutoff date, 33 patients had reached the time point for PFS6 assessment. Twelve patients were progression-free at 6 months, yielding a PFS6 of 47.7%. The remaining data will mature by July 2018, and further improvement in PFS6 may occur. At 6 months, 30 patients were still alive, resulting in a 6-month overall survival (OS) of 89%; at 12 months, 12 patients were alive (12-month OS, 65%).
The preliminary results reported here suggest that the combination of durvalumab and PLD has a tolerable safety profile and promising efficacy in women with platinum-resistant ovarian cancer. The final PFS6 and other translational end points are pending additional data.
- Lee J-M, et al. J Clin Oncol. 2017;35:2193-2202.
- O’Cearbhaill RE, et al. ESMO 2018. Abstract 945P.