Boer Shan

Anlotinib in patients with recurrent platinum resistant/refractory ovarian cancer: a prospective, single arm, phase II study

This study aimed to prospectively evaluate the efficacy and safety of anlotinib in patients with platinum resistant/refractory ovarian cancer. In this prospective, single arm, phase II study, patients with platinum resistant/refractory ovarian cancer received anlotinib (12 mg once daily; days 1-14; 21 days per cycle) until disease progression, unacceptable toxicity, or study withdrawal. The study was conducted between May 2019 and May 2021. The primary endpoint was objective response rate. Secondary endpoints were disease control rate, progression free survival, overall survival, and safety. An exploratory biomarker analysis was performed to evaluate the correlation of baseline TP53 mutation status with outcomes. 33 of 34 enrolled patients received at least one dose of anlotinib. The objective response rate was 31.2% (95% confidence interval (CI) 16.1% to 50.0%), with 2 (6.3%) complete and 8 (25.0%) partial responses. In total, 14 (43.8%) patients achieved stable disease, resulting in a disease control rate of 75.0% (95% CI 56.6% to 88.5%). With a median follow-up of 4.6 months (range 0.5-17.2) at data cut-off (September 16, 2022), median progression free survival was 5.3 months (95% CI 4.04 to 6.56) and median overall survival was not reached. In a subgroup analysis, patients with a TP53 mutation showed a trend towards worse progression free survival than those with the wild-type TP53 (4.4 months vs 8.4 months; hazard ratio 2.48 (95% CI 0.91 to 6.76), p=0.067). Common adverse events were hypertension (42.4%), hand-foot syndrome (27.3%), and fatigue (24.2%). Grade 3 events were reported in 3 (9.1%) patients and no grade 4-5 events or deaths were observed. Anlotinib showed antitumor activity with an acceptable safety profile in patients with platinum resistant/refractory ovarian cancer, and it might be a potential treatment in this population.

Integrative genomic and transcriptomic analysis reveals immune subtypes and prognostic markers in ovarian clear cell carcinoma

Abstract Background We performed an integrative genomic and transcriptomic profiling to identify molecular subtypes and prognostic markers with special focus on immune-related pathways. Methods Totally, 50 Chinese patients were subjected to targeted next-generation sequencing and transcriptomic sequencing. Results Two distinct subgroups were identified as immune (22.0%) and non-immune (78.0%) based on the immune-pathway related hierarchical clustering. Surprisingly, patients with immune subtype had a significantly worse survival. The prognostic capacity was validated in external cohorts. The immune group had higher expression of genes involved in pro-inflammation and checkpoints. PD-1 signalling pathway was enriched in the immune subtype. Besides, the immune cluster presented enriched expression of genes involved in epithelial-mesenchymal transition, angiogenesis and PI3K-AKT-mTOR signalling, while the non-immune subtype had higher expression of metabolic pathways. The immune subtype had a higher mutation rate of PIK3CA though significance was not achieved. Lastly, we established a prognostic immune signature for overall survival. Interestingly, the immune signature could also be applied to renal clear cell carcinoma, but not to other histologic subtype of ovarian cancer. Conclusions An immune subtype of OCCC was identified with poor survival and enrichment of PD-1 and PI3K-AKT-mTOR signalling. We constructed and validated a robust prognostic immune signature of OCCC patients.