Targeting homologous recombination deficiency with intensified chemotherapy versus standard chemotherapy followed by olaparib in stage III breast cancer (SUBITO): an open-label, randomised, controlled, phase 3 trial

Phase 3 trial comparing intensified chemotherapy with autologous stem cell rescue to standard chemotherapy followed by olaparib in HRD breast cancer

The randomised phase 3 SUBITO trial (174 patients, including germline BRCA1/2 carriers) compared intensified alkylating chemotherapy with autologous stem cell rescue to standard chemotherapy followed by one year of olaparib, in stage III HER2-negative breast cancer with homologous recombination deficiency. Four-year overall survival was identical between arms (77.0% vs 76.4%; HR 1.11), with markedly higher toxicity in the intensified arm. Intensified chemotherapy therefore provides no benefit over the standard strategy plus olaparib. Targeting HRD yields excellent survival outcomes in this otherwise aggressive subgroup.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

A strong practical result: toxic treatment escalation can be abandoned in favor of standard chemotherapy followed by olaparib, with no survival loss. For the oncogeneticist, this reinforces the value of rapidly identifying HRD / germline BRCA status at diagnosis of stage III breast cancer, as it directly determines a PARP-inhibitor maintenance option of proven efficacy.