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Table of Contents
LETTER TO EDITOR
Year : 2021  |  Volume : 4  |  Issue : 3  |  Page : 600-601

Adjuvant olaparib in germline BRCA-mutated breast cancer – Standard of care for all?


Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India

Date of Submission24-Aug-2021
Date of Decision02-Sep-2021
Date of Acceptance05-Sep-2021
Date of Web Publication08-Oct-2021

Correspondence Address:
Ajay Gogia
Department of Medical Oncology, All India Institute of Medical Sciences, Dr. B.R. Ambedkar Institute Rotary Cancer Hospital, New Delhi - 110 029
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/crst.crst_202_21

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How to cite this article:
Ganguly S, Gogia A. Adjuvant olaparib in germline BRCA-mutated breast cancer – Standard of care for all?. Cancer Res Stat Treat 2021;4:600-1

How to cite this URL:
Ganguly S, Gogia A. Adjuvant olaparib in germline BRCA-mutated breast cancer – Standard of care for all?. Cancer Res Stat Treat [serial online] 2021 [cited 2021 Dec 9];4:600-1. Available from: https://www.crstonline.com/text.asp?2021/4/3/600/327788



In the recently published OlympiA trial, Tutt et al.[1] reported improved invasive disease-free survival with adjuvant olaparib in high-risk human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with germline BRCA1/2 mutations. We note that in patients with hormone receptor-positive tumors (325/1836; 17.7% of the cohort), the benefit of adjuvant olaparib could not be conclusively demonstrated. Coadministration of olaparib and tamoxifen is known to decrease the exposure to olaparib and increase the exposure to tamoxifen.[2] This relevant pharmacokinetic interaction needs to be further explored for its effect on disease recurrence rate and hormonal therapy-related adverse events. For the hormone receptor-positive subgroup, the median follow-up of 2.5 years was also relatively short for an adequate number of events of disease recurrence. In addition, it is essential to monitor for potential concerning adverse events of olaparib like myelodysplastic syndrome and/or acute myeloid leukemia for which longer follow-up is imperative.

We also observed that in the subgroup of patients with prior exposure to platinum compounds, the use of adjuvant olaparib failed to demonstrate any benefit. Breast tumors with BRCA-deficiency are known to be uniquely sensitive to platinum compounds.[3] The OlympiA trial specifically included patients who did not achieve pathological complete response post neoadjuvant therapy. This suggests that patients with prior suboptimal response to platinum compounds are unlikely to derive any benefit from adjuvant poly adenosine diphosphate-ribose polymerase (PARP) inhibition. Rather, platinum sensitivity may be considered as a predictive biomarker for subsequent sensitivity to PARP inhibitors. The efficacy of adjuvant olaparib needs to be explored in those with a prior good response to platinum compounds.

Conversely, the use of adjuvant capecitabine has been shown to improve disease-free survival in patients with triple-negative breast cancer (TNBC) with residual disease post neoadjuvant therapy.[4] Hence, for patients with a suboptimal response to neoadjuvant platinum compounds, the use of adjuvant capecitabine may be a preferable alternative. Considering the cost implications of olaparib vis-à-vis capecitabine, capecitabine may be more cost effective, especially in low/middle-income countries. The relative efficacy and cost-effectiveness analysis of olaparib over capecitabine should be investigated.

With the current evidence showing a benefit of atezolizumab in the neoadjuvant treatment of early TNBC,[5],[6] immunotherapy is already incorporated in the treatment algorithm of early TNBC. BRCA-deficient breast tumors, especially those with BRCA1-mutations, have increased expression of immune checkpoint receptors with possible enhanced sensitivity to immunotherapy. The effect of immune checkpoint expression on the benefit of PARP inhibitors as well as synergism of immunotherapy and PARP inhibitors is also worth evaluating.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Tutt AN, Garber JE, Kaufman B, Viale G, Fumagalli D, Rastogi P, et al. Adjuvant olaparib for patients with BRCA1- or BRCA2 – Mutated breast cancer. N Engl J Med 2021;384:2394-405.  Back to cited text no. 1
    
2.
Plummer R, Verheul HM, De Vos FY, Leunen K, Molife LR, Rolfo C, et al. Pharmacokinetic effects and safety of olaparib administered with endocrine therapy: A phase I study in patients with advanced solid tumours. Adv Ther 2018;35:1945-64.  Back to cited text no. 2
    
3.
Torrisi R, Zuradelli M, Agostinetto E, Masci G, Losurdo A, De Sanctis R, et al. Platinum salts in the treatment of BRCA-associated breast cancer: A true targeted chemotherapy? Crit Rev Oncol Hematol 2019;135:66-75.  Back to cited text no. 3
    
4.
Masuda N, Lee SJ, Ohtani S, Im YH, Lee ES, Yokota I, et al. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med 2017;376:2147-59.  Back to cited text no. 4
    
5.
Mittendorf EA, Zhang H, Barrios CH, Saji S, Jung KH, Hegg R, et al. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): A randomised, double-blind, phase 3 trial. Lancet 2020;396:1090-100.  Back to cited text no. 5
    
6.
Arora S, Gogia A. Recent updates in systemic therapy of breast cancer: A brief narrative review. Cancer Res Stat Treat 2021;4:99-109.  Back to cited text no. 6
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