Other Roles for the HRD Assay

Despite having no clinical role for selecting chemotherapy for TNBC, the HRD assay may have utility for selecting other therapies involved with DNA damage — PARP inhibitors, for example.

SWOG S1416 (ClinicalTrials.gov Identifier: NCT02595905) compared cisplatin treatments for metastatic TNBC or germline BRCA1/2-associated metastatic breast cancer plus either the PARP inhibitor veliparib or placebo.9 Biomarkers used in the study identified a subgroup of BRCA wild-type TNBC that benefited from the combination treatment.

“The HRD assay or HRD biomarkers may be helpful in selecting patients who would benefit from PARP inhibitor addition to platinum-based chemotherapy,” SWOG S1416 study author Dr Sharma said, noting that the assay is not clinically approved for this indication.

The HRD assay is also included as a companion diagnostic in the approval for the PARP inhibitor olaparib for advanced ovarian cancer that is HRD positive. More recently, the role of HRD is being explored in prostate cancer as well.


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“There is still great interest in the concept of HRD,” Dr Mayer said. “We will continue to analyze data from the TBCRC study to see if other biomarkers or signatures may have greater precision in identifying tumors that are more or less sensitive to specific chemotherapy.”

References

  1. Mayer EL, Abramson V, Jankowitz R, et al. TBCRC 020: A phase II study of preoperative cisplatin vs. paclitaxel in triple-negative breast cancer: evaluating the homologous recombination deficiency (HRD) biomarker. Annals Oncol. Published online August 13, 2020. doi:10.1016/j.annonc.2020.08.2064
  2. Birkbak NJ, Wang ZC, Kim JY, et al. Telomeric allelic imbalance indicates defective DNA repair and sensitivity to DNA-damaging agents. Cancer Discov. 2012;2:366-375. doi:10.1158/2159-8290.CD-11-0206
  3. Coleman RL, Oza AM, Lorusso D, et al. ARIEL3 Investigators. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390(10106):1949-1961. doi:10.1016/S0140-6736(17)32440-6
  4. Coleman RL, Fleming GF, Brady MF, et al. Veliparib with first-line chemotherapy and as maintenance therapy in ovarian cancer. N Engl J Med. 2019;381(25):2403-2415. doi:10.1056/NEJMoa1909707
  5. Mirza MR, Monk BJ, Herrstedt J, et al. ENGOT-OV16/NOVA Investigators. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med. 2016;375(22):2154-2164. doi:10.1056/NEJMoa1611310
  6. Ray-Coquard I, Pautier P, Pignata S, et al. PAOLA-1 Investigators. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. N Engl J Med. 2019;381(25):2416-2428. doi:10.1056/NEJMoa1911361
  7. Loibl S, Weber KE, Timms KM, et al. Survival analysis of carboplatin added to an anthracycline/taxane-based neoadjuvant chemotherapy and HRD score as a predictor of response-final results from GeparSixto. Ann Oncol. 2020;29:2341-2347.  doi:10.1093/annonc/mdy460
  8. Telli ML, Metzger O, Timms K, et al. Evaluation of homologous recombination deficiency (HRD) status with pathological response to carboplatin +/- veliparib in BrighTNess, a randomized phase 3 study in early stage TNBC. J Clin Oncol. doi:10.1200/JCO.2018.36.15_suppl.519
  9. Sharma P, Rodler E, Barlow WE, et al. Results of a phase II randomized trial of cisplatin +/- veliparib in metastatic triple-negative breast cancer (TNBC) and/or germline BRCA-associated breast cancer (SWOG S1416). J Clin Oncol. 2020;38(15_suppl):1001-1001. doi:10.1200 /JCO.2020.38.15_suppl.1001