Pembrolizumab/Anlotinib Combo Has Efficacy in Refractory or Platinum-Resistant Recurrent High-Grade Serous Ovarian Cancer

Pembrolizumab (Keytruda) monotherapy and in combination with anlotinib (AL3818) demonstrated encouraging efficacy and safety when administered to patients with refractory or platinum-resistant recurrent high-grade serous ovarian cancer, according to data from a nonrandomized phase 2 trial presented during the 2022 ASCO Annual Meeting.

Data showed that among 15 patients who received the doublet, the median progression-free survival (PFS) is 13.0 months (95% CI, 11.11-14.89). The combination elicited an objective response rate (ORR) of 33.3% (95% CI, 0.118-0.616), which was comprised of partial responses; 66.7% of patients achieved stable disease and no patients experienced disease progression. The disease control rate (DCR) was 100% (95% CI, 0.782-1.0).

In the 18 patients who received pembrolizumab monotherapy, the median PFS was 8.0 months (95% CI, 5.93-10.07). The ORR was 0%; 88.9% achieved disease stability and 11.1% experienced disease progression. Pembrolizumab resulted in a DCR of 88.9% (95% CI, 0.653-0.986).

“Our study aims to examine the efficacy and safety of anlotinib [plus] pembrolizumab combination therapy as a treatment for refractory or platinum-resistant recurrent high-grade ovarian cancer,” lead study author Man Jiang, of The Affiliated Hospital of Qingdao University, and colleagues, wrote in a presentation on the data.

Prior research efforts have suggested that anlotinib has synergistic effects when combined with anti–PD-1 agents by altering the tumor microenvironment.

The phase 2 trial enrolled patients with refractory or platinum-resistant recurrent high-grade serous ovarian cancer between the ages of 18 years and 75 years who had an ECOG performance status of 0 or 1. All patients had a PD-L1 combined positive score of 1 to 4.

Patients were enrolled to arm 1 or arm 2. Those in arm 1 received anlotinib at 12 mg daily for days 1 through 14 and pembrolizumab at 200 mg every 3 weeks (n = 15), and those in arm 2 were given pembrolizumab alone at 200 mg every 3 weeks (n = 18).

The primary end points of the trial were PFS and overall survival (OS), and secondary end points comprised ORR, DCR, and safety.

The medium age of patients was 58.55 years (interquartile range, 28-75), with a body mass index of 20.4 +/- 3.4 kg/m² (95% CI, 16.8-29.7). All patients had high-grade serous carcinoma, all had surgery, tumor mutational burden of less than 10, non–microsatellite stability–high disease, a Ki67 of 30% or less, and assessable lesion that were 2 cm or smaller. Regarding ECOG performance status, 63.6% of patients had a status of 1 and 36.4% had a status of 0.

Additional data showed that the median OS was not yet reached in either arm.

Investigators also performed second-generation sequencing with tumor tissue samples. They found that those who harbored an ARID1A mutation experienced a significant survival benefit with pembrolizumab monotherapy vs those with wild-type disease, with a median PFS of 11.0 months (95% CI, 9.7-12.3) and 5.5 months (95% CI, 4.5-6.6), respectively (P = .04).

In the pembrolizumab/anlotinib arm, the median PFS for those with an ARID1A mutation was 14.0 months (95% CI, 9.9-18.1) vs 13.0 months (95% CI, 8.7-17.3) in those with wildtype disease (P = .20); this difference was not significant.

“The ARID1A is a potential biomarker for predicting the efficacy of pembrolizumab monotherapy in ovarian cancer,” the study authors concluded.

Reference

Jiang M, Li T, Wang G, et al. Efficacy and safety of pembrolizumab in combination with anlotinib in the treatment of refractory or recurrent high-grade serous ovarian cancer: a phase 2 nonrandomized clinical trial. J Clin Oncol. 2022;40(suppl 16):5543. doi:10.1200/JCO.2022.40.16_suppl.5543