Conducted in 74 hospitals throughout the United Kingdom, TNT (NCT00532727) was a phase III, parallel group, open-label randomised controlled trial with preplanned biomarker subgroup analyses. The results are published on 30 April 2018 in the Nature Medicine. The authors wrote that the PARP inhibitor olaparib is now approved in advanced germline-mutated BRCA1/2 breast cancer, but this treatment may remain unaffordable to many health care systems and patients for many years. It remains unknown how potent PARP1-trapping inhibitors would compare with platinums in this setting, but the results of the TNT trialprovide evidence that a widely available, affordable off-patent biomarker, which is enriched in the triple-negative breast cancers (TNBCs) prevalent in many developing countries, has utility in selecting a patient population that could benefit during this period from the biologically targeted use of a highly active and inexpensive platinum chemotherapy agent rather than the current licensed standard-of-care chemotherapies for breast cancer.
The authors wrote in study background that germline mutations in BRCA1/2 predispose individuals to germline-mutated BRCA1/2 breast cancer by impairing homologous recombination (HR) and causing genomic instability. HR also repairs DNA lesions caused by platinum agents and PARP inhibitors. TNBCs harbour subpopulations with BRCA1/2 mutations, hypothesized to be especially platinum-sensitive. Cancers in putative ‘BRCAness’ subgroups (tumours with BRCA1 methylation, low levels of BRCA1 mRNA, or mutational signatures for HR deficiency and those with basal phenotypes) may also be sensitive to platinum.
Source: ESMO
