ESMO 2019 — Expert commentary: tackling the treatment options in triple negative metastatic breast cancer

  • Daniela Ovadia — Agenzia Zoe
  • Oncology Conference reports
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Suzette Delaloge, Associate Professor of Medical Oncology, Head of the Breast Cancer Department, Hôpital Gustave Roussy, Paris, France

  • The choice of the treatment option in triple-negative breast cancer (TNBC) is one of the major challenges in oncology and requires a good knowledge of the molecular signatures of the tumour.
  • Metastatic TNBC still has a very poor outcome. According to the multicentric French National study ESME COHORT on 22 000 women from 2008 to 2016, median overall survival (OS) in TNBC is around 15 months, while median OS in HER2+ patients is around 50 months and around 43 months in HR+, HER2- patients.
  • During her presentation at ESMO, Dr Delaloge challenged the audience, asking them which test they would require for a 43-year-old patient with metastatic breast cancer. The list included PD-L1 IHC assessment; TILs; AR expression; a tumour panel including HRD and major genomic hits; a germline search of BRCA1/2 alteration; a circulating panel including HER2, PIK3CA, and AKT; and a transcriptome profiling to identify TNBC subtype and IHC for a targetable epithelial antigen. Only the search for BRCA mutations reached unanimity, while the other markers were considered only by subgroups of clinicians.
  • The choice could be influenced by the availability of both the tests and the targeted therapies, but all the mentioned tests can be useful to make a proper treatment choice.
  • In a PD-L1+ patient, the decision tree would suggest proceeding with PD-L1 inhibition plus chemotherapy. New data from KEYNOTE 086 suggest that also a PD1/PD-L1 inhibitor as a single agent therapy could be a good choice. The IMpassion130 study shows also that PD-L1 status predicts the benefit of atezolizumab.
  • In BRCA mutations, PARP inhibitors are the first-line choice, or platinum if PARP inhibitors are not available. The OlympiAD and EMBRACA trials, among others, show that both olaparib and talazoparib improve response rate in germline BRCA mutated metastatic breast cancer patients compared with chemotherapy.
  • What if both PD-L1 and BRCA1/2 are positive? We can go for PD-L1 inhibition plus chemotherapy or use an innovative strategy combining PARP inhibition with immunotherapy, but only if we have enough money or health coverage for these highly expensive treatments.
  • In HRD alterations, we can consider platinum. We are waiting for the results of phase 3 trials to find new options.
  • If the PI3K/AKT pathway is altered, in the future we will probably use chemotherapy and/or AKT inhibitors. Phase 3 trials (like LOTUS and PAKT) are ongoing and we are waiting for the final results.
  • Finally, if the androgen receptor (AR) is positive, we hope in the future, to be able to target it specifically. There are a few ongoing phase 2 studies such as START that should give us a proof of concept for this strategy.
  • In the future we could also use antibody-drug conjugation, a novel strategy that seems promising and will allow delivering high doses of effective drugs selectively to tumour cells. We are waiting for the results of the phase 3 ASCENT trial using sacituzumab govitecan.
  • Dr Delaloge said that the landscape is complex and constantly changing, and clinicians could have trouble deciding the best treatment for their patients, considering the costs and the benefits in terms of overall survival. Updated tools, such as decision-making trees, could be very helpful.