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PARP inhibitor plus chemotherapy versus chemotherapy alone in patients with triple-negative breast cancer: a systematic review and meta-analysis based on randomized controlled trials

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Abstract

Background

Chemotherapy is the standard treatment for triple-negative breast cancer (TNBC). Whether the addition of PARP inhibitors improves treatment efficacy remains controversial clinically. Thus, we performed a meta-analysis to compare the efficacy and safety of combination treatment (PC) and chemotherapy alone (CA).

Methods

Relevant studies were identified through searches of 7 databases. The primary endpoints were progression-free survival (PFS) and overall survival (OS).

Results

We screened 317 studies and included seven RCTs involving 2091 patients in the final analysis. PC tended to have better efficacy than CA according to PFS (HR [hazard ratio]: 0.83 [0.75, 0.93], p = 0.001), OS (HR: 0.89 [0.76,1.03], p = 0.11) and overall response rate (ORR) (RR [risk ratio]: 1.19 [0.97,1.46], p = 0.10). However, grade 3–5 AEs (RR: 1.50 [0.87,2.61], p = 0.15) were observed in the PC group. In the PC arm, the 10 most-reported grade 3–5 AEs were neutropenia (62.8%), anemia (28.5%), thrombocytopenia (26.4%), lymphopenia (19.05%), leukopenia (16.9%), fatigue (5%), heart failure (4.76%), lung infection (4.76%), thromboembolic events (4.76%) and ventricular tachycardia (4.76%). Similar results for pathological complete response (pCR), total AEs, rate of complete response (CR), stable disease (SD) and progressive disease (PD), breast conservation rate (BCR), and drug discontinuation (DD) rate were found between the two groups.

Conclusions

For TNBC treatment, the combination of PARP inhibitors and chemotherapy appears to be superior to chemotherapy alone with better antitumor efficacy. However, its higher rate of AEs needs to be taken seriously. More high-quality RCTs are needed to confirm these results.

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Availability of data and materials

The data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

AEs:

Adverse effects

BCR:

Breast conservation rate

BRCA:

Breast cancer susceptibility gene

CA:

Chemotherapy alone

CR:

Complete response

CI:

Confidence interval

DD:

Drug discontinuation

DCR:

Disease control rate

ER:

Estrogen receptor

ECOG:

Eastern Cooperative Oncology Group

GRADE:

Grades of Recommendations Assessment, Development and Evaluation

HR:

Hazard ratio

HER2:

Human epidermal growth factor receptor-2

OS:

Overall survival

ORR:

Overall response rate

PARP:

Poly ADP-ribose polymerase

PARPi:

Poly ADP-ribose polymerase inhibitor

PC:

PARP inhibitor plus chemotherapy

PFS:

Progression-free study

pCR:

Pathological complete response

PD:

Progressive disease

PR:

Progesterone receptor

PR:

Partial response

PRISMA:

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

RCT:

Randomised controlled study

RR:

Risk ratio

SD:

Stable disease

SSB:

Single-strand break

TNBC:

Triple-negative breast cancer

TNM:

Tumor node metastasis

References

  1. Siegel RL, Miller KD, Fuchs HE, Jemal A (2022) Cancer statistics, 2022. CA Cancer J Clin 72(1):7–33

    Article  PubMed  Google Scholar 

  2. Fahad UM (2019) Breast cancer: current perspectives on the disease status. Adv Exp Med Biol 1152:51–64

    Article  Google Scholar 

  3. Budh DP, Sapra A (2022) Breast cancer screening. 2022 17. In: StatPearls. Treasure Island (FL): StatPearls Publishing.

  4. Ben Aziz M, Mukhdomi T (2022) Regional anesthesia for breast reconstruction. 2022 19. In: StatPearls. Treasure Island (FL): StatPearls Publishing.

  5. Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH et al (2013) Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol 31(31):3997–4013

    Article  PubMed  Google Scholar 

  6. Yin L, Duan JJ, Bian XW, Yu SC (2020) Triple-negative breast cancer molecular subtyping and treatment progress. Breast Cancer Res 22(1):61

    Article  PubMed  PubMed Central  Google Scholar 

  7. Morris GJ, Naidu S, Topham AK, Guiles F, Xu Y, McCue P et al (2007) Differences in breast carcinoma characteristics in newly diagnosed African-American and Caucasian patients: a single-institution compilation compared with the National Cancer Institute’s Surveillance, Epidemiology, and End Results database. Cancer 110(4):876–884

    Article  PubMed  Google Scholar 

  8. Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA et al (2007) Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 13(15 Pt 1):4429–4434

    Article  PubMed  Google Scholar 

  9. Bergin ART, Loi S (2019) Triple-negative breast cancer: recent treatment advances. F1000Res 8:F1000 Faculty Rev-1342.

  10. Chen Z, Wang X, Li X, Zhou Y, Chen K (2021) Deep exploration of PARP inhibitors in breast cancer: monotherapy and combination therapy. J Int Med Res 49(2):300060521991019

    Article  CAS  PubMed  Google Scholar 

  11. Bjarnason NH, Hitz M, Jorgensen NR, Vestergaard P (2008) Adverse bone effects during pharmacological breast cancer therapy. Acta Oncol 47(4):747–754

    Article  CAS  PubMed  Google Scholar 

  12. Chaudhary LN, Wilkinson KH, Kong A (2018) Triple-negative breast cancer: who should receive neoadjuvant chemotherapy? Surg Oncol Clin N Am 27(1):141–153

    Article  PubMed  Google Scholar 

  13. JabbarzadehKaboli P, Salimian F, Aghapour S, Xiang S, Zhao Q, Li M et al (2020) Akt-targeted therapy as a promising strategy to overcome drug resistance in breast cancer—a comprehensive review from chemotherapy to immunotherapy. Pharmacol Res 156:104806

    Article  CAS  Google Scholar 

  14. Lebert JM, Lester R, Powell E, Seal M, McCarthy J (2018) Advances in the systemic treatment of triple-negative breast cancer. Curr Oncol 25(Suppl 1):S142–S150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Keenan TE, Tolaney SM (2020) Role of immunotherapy in triple-negative breast cancer. J Natl Compr Canc Netw 18(4):479–489

    Article  CAS  PubMed  Google Scholar 

  16. Rizzo A, Ricci AD (2022) Biomarkers for breast cancer immunotherapy: PD-L1, TILs, and beyond. Expert Opin Investig Drugs 31(6):549–555

    Article  CAS  PubMed  Google Scholar 

  17. Rizzo A, Ricci AD, Lanotte L, Lombardi L, Di Federico A, Brandi G et al (2022) Immune-based combinations for metastatic triple negative breast cancer in clinical trials: current knowledge and therapeutic prospects. Expert Opin Investig Drugs 31(6):557–565

    Article  CAS  PubMed  Google Scholar 

  18. Massafra R, Bove S, La Forgia D, Comes MC, Didonna V, Gatta G et al (2022) An invasive disease event-free survival analysis to investigate Ki67 role with respect to breast cancer patients’ age: a retrospective cohort study. Cancers (Basel) 14(9):2215

    Article  CAS  PubMed  Google Scholar 

  19. Rizzo A, Cusmai A, Acquafredda S, Rinaldi L, Palmiotti G (2022) Ladiratuzumab vedotin for metastatic triple negative cancer: preliminary results, key challenges, and clinical potential. Expert Opin Investig Drugs 31(6):495–498

    Article  CAS  PubMed  Google Scholar 

  20. Pantelidou C, Sonzogni O, De Oliveria TM, Mehta AK, Kothari A, Wang D et al (2019) PARP inhibitor efficacy depends on CD8+ T-cell recruitment via intratumoral STING pathway activation in BRCA-deficient models of triple-negative breast cancer. Cancer Discov 9(6):722–737

    Article  PubMed  PubMed Central  Google Scholar 

  21. Eikesdal HP, Yndestad S, Elzawahry A, Llop-Guevara A, Gilje B, Blix ES et al (2021) Olaparib monotherapy as primary treatment in unselected triple negative breast cancer. Ann Oncol 32(2):240–249

    Article  CAS  PubMed  Google Scholar 

  22. Topçul M, Çeti NİL, ÖzbaşTuran S, KolusayinOzar MÖ (2018) In vitro cytotoxic effect of PARP inhibitor alone and in combination with nab-paclitaxel on triple-negative and luminal A breast cancer cells. Oncol Rep 40(1):527–535

    PubMed  Google Scholar 

  23. D’Andrea AD (2018) Mechanisms of PARP inhibitor sensitivity and resistance. DNA Repair (Amst) 71:172–176

    Article  CAS  PubMed  Google Scholar 

  24. Sonnenblick A, de Azambuja E, Azim HA Jr, Piccart M (2015) An update on PARP inhibitors–moving to the adjuvant setting. Nat Rev Clin Oncol 12(1):27–41

    Article  CAS  PubMed  Google Scholar 

  25. Diéras V, Han HS, Kaufman B, Wildiers H, Friedlander M, Ayoub JP et al (2020) Veliparib with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer (BROCADE3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 21(10):1269–1282

    Article  PubMed  Google Scholar 

  26. Loibl S, O’Shaughnessy J, Untch M, Sikov WM, Rugo HS, McKee MD et al (2018) Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess): a randomised, phase 3 trial. Lancet Oncol 19(4):497–509

    Article  CAS  PubMed  Google Scholar 

  27. Rugo HS, Olopade OI, DeMichele A, Yau C, Van’t Veer LJ, Buxton MB et al (2016) Adaptive randomization of veliparib-carboplatin treatment in breast cancer. N Engl J Med 375(1):23–34

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kummar S, Wade JL, Oza AM, Sullivan D, Chen AP, Gandara DR et al (2016) Randomized phase II trial of cyclophosphamide and the oral poly (ADP-ribose) polymerase inhibitor veliparib in patients with recurrent, advanced triple-negative breast cancer. Invest New Drugs 34(3):355–363

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. O’Shaughnessy J, Osborne C, Pippen JE, Yoffe M, Patt D, Rocha C et al (2011) Iniparib plus chemotherapy in metastatic triple-negative breast cancer. N Engl J Med 364(3):205–214

    Article  CAS  PubMed  Google Scholar 

  30. O’Shaughnessy J, Schwartzberg L, Danso MA, Miller KD, Rugo HS, Neubauer M et al (2014) Phase III study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer. J Clin Oncol 32(34):3840–3847

    Article  CAS  PubMed  Google Scholar 

  31. Llombart-Cussac A, Bermejo B, Villanueva C, Delaloge S, Morales S, Balmaña J et al (2015) SOLTI NeoPARP: a phase II randomized study of two schedules of iniparib plus paclitaxel versus paclitaxel alone as neoadjuvant therapy in patients with triple-negative breast cancer. Breast Cancer Res Treat 154(2):351–357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ et al (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17(1):1–12

    Article  CAS  PubMed  Google Scholar 

  33. Guyatt GH, Oxman AD, Schünemann HJ, Tugwell P, Knottnerus A (2011) GRADE guidelines: a new series of articles in the Journal of Clinical Epidemiology. J Clin Epidemiol 64(4):380–382

    Article  PubMed  Google Scholar 

  34. Litton JK, Rugo HS, Ettl J, Hurvitz SA, Gonçalves A, Lee KH et al (2018) Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med 379(8):753–763

    Article  CAS  PubMed  Google Scholar 

  35. Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N et al (2017) Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med 377(6):523–533

    Article  CAS  PubMed  Google Scholar 

  36. Tutt A, Tovey H, Cheang MCU, Kernaghan S, Kilburn L, Gazinska P et al (2018) Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial. Nat Med 24(5):628–637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Hashimoto K, Tamura K (2010) Breakthrough breast cancer treatment-PARP inhibitor, BRCA, and triple negative breast cancer. Gan To Kagaku Ryoho 37(7):1187–1191

    PubMed  Google Scholar 

  38. Sikov WM, Berry DA, Perou CM, Singh B, Cirrincione CT, Tolaney SM et al (2015) Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). J Clin Oncol 33(1):13–21

    Article  CAS  PubMed  Google Scholar 

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Funding

This study was supported by National Natural Science Foundation of China (NSFC, Grant number: 81560345) and Natural Science Foundation of Jiangxi Province (Grant number: 20212BAB206050, 20192ACBL21036). Role of the Funding: The funding had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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Authors and Affiliations

  1. Department of Thoracic Surgery, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang, 330006, China

    Chenxi Li, Yiping Wei & Wenxiong Zhang

  2. Jiangxi Medical College, Nanchang University, Nanchang, 330006, China

    Chenxi Li, Meiqi Hao, Zige Fang & Jiatong Ding

  3. Department of Breast Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China

    Meiqi Hao, Zige Fang, Jiatong Ding & Sijia Duan

  4. Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China

    Fengming Yi

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Contributions

WZ had full access to all the data in the manuscript and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors read and approved the final manuscript. Concept and design: all authors. Acquisition, analysis, or interpretation of data: all authors. Drafting of the manuscript: CL and WZ. Critical revision of the manuscript for important intellectual content: CL, SD and FY. Statistical analysis: CL, MH, ZF and JD. Supervision: CL and WZ.

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Correspondence to Wenxiong Zhang.

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Supplementary Information

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Figure S1 Risk of bias graph for included studies (TIF 4525 KB)

Figure S2 Forest plots of breast conservation rates associated with PC vs CA (TIF 1648 KB)

280_2023_4506_MOESM3_ESM.tif

Figure S3 Forest plots of RR of all-grade AEs associated with PC vs CA (including subgroup analysis of 10 most-reported AEs according to the combination of both arms) (TIF 16933 KB)

280_2023_4506_MOESM4_ESM.tif

Figure S4 Forest plots of RR of grade 3-5 AEs associated with PC vs CA (including subgroup analysis of 10 most-reported grade 3-5 AEs according to the combination of both arms) (TIF 16825 KB)

Figure S5 Sensitivity analysis of pCR and PFS (TIF 982 KB)

Figure S6 Publication bias of pCR and PFS (TIF 483 KB)

Table S1 PRISMA 2009 Checklist (DOC 63 KB)

Table S2 Methodological quality assessments of the included studies (DOCX 22 KB)

Table S3 Jadad quality assessment of all included studies (DOCX 12 KB)

Table S4 GRADE quality assessment by therapeutic strategy and for the outcomes (DOCX 47 KB)

Table S5 Total adverse events with an incidence of greater than 10% in the PC group (DOCX 17 KB)

Table S6 Total adverse events with an incidence of greater than 10% in the CA group (DOCX 17 KB)

Table S7 Grade 3-5 adverse events with an incidence of greater than 1% in the PC group (DOCX 16 KB)

Table S8 Grade 3-5 adverse events with an incidence of greater than 1% in the CA group (DOCX 15 KB)

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Li, C., Hao, M., Fang, Z. et al. PARP inhibitor plus chemotherapy versus chemotherapy alone in patients with triple-negative breast cancer: a systematic review and meta-analysis based on randomized controlled trials. Cancer Chemother Pharmacol 91, 203–217 (2023). https://doi.org/10.1007/s00280-023-04506-x

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  • DOI: https://doi.org/10.1007/s00280-023-04506-x

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