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These include prior PARP benefit and HRD in CAPRI, CCNE1 amplification in the adavosertib phase II study, prespecified DDR loss-of-function alterations in camonsertib development, and Cyclin E1 protein expression in current azenosertib trials.[1,4,7,8,11] For clinical-trial evaluation, potentially relevant information includes tumor histology, platinum sensitivity when applicable, previous PARP exposure and duration of benefit, germline and somatic BRCA1/2 status, broader HRR findings, CCNE1 or Cyclin E1 status when required by a protocol, ATM protein loss or allelic context, and other trial-specific genomic eligibility criteria.[1,4,5,7-9,11] A commercial sequencing report showing a DDR-associated variant should not automatically be interpreted as evidence of sensitivity to an ATR or WEE1 inhibitor.[4,5] Practical Clinical Approach The available evidence does not establish ATR- or WEE1-directed treatment as a routine standard strategy after PARP inhibitor progression
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