What second-line therapy would you recommend for a patient with a pathogenic BRCA-1 mutation and stage IIIA fallopian tube high-grade serous carcinoma, who underwent R0 cytoreduction followed by 6 cycles of carboplatin/paclitaxel with complete response, who has now progressed 13 months into olaparib maintenance?   

How does the following influence your recommendation?

- The post-hoc analyses of SOLO2/ENGO Ov-21 trial indicated that following progression from maintenance olaparib in the recurrent setting the efficacy of platinum-based chemotx seems to be reduced (i.e., development of PARPi resistance seems to predict development of platinum resistance).  

- The CAPRI trial suggested the the combination of olaparib and ceralasertib is well tolerated and has significant activity in HR-deficient platinum-sensitive HGSOC who benefited, but then progressed with PARPi. 

- There are no promoters of synthetic lethality (e.g., inhibitors of WEE1, ATR, CHK1, or ATM kinase) that are on the market and she is not willing to travel out of state for a clinical trial.