RESEARCH POSTER PRESENTATION DESIGN © 2019

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INTRODUCTION OBJECTIVES

Breast cancer is the most commonly diagnosedcancer and is the leading cause of cancer death inwomen worldwide. Both talazoparib and olaparib areapproved by the US Food and Drug Administration fortreating BRCA (breast cancer 1, early onset)-mutatedHER2 (erb-b2 receptor tyrosine kinase 2)-negativemetastatic or advanced breast cancer. However, theoptimal choice of first-line treatment has not beendetermined.

MATERIAL AND METHODS

REFERENCES

we performed a network meta-analysis (NMA) to compare single-agent PARPi for advanced breast cancer.

Overall, the database search identified 15,831 studies; 4,548studies were excluded due to duplicate records and 11,238studies were excluded based on the selection criteria after readingthe title and abstract. Subsequently, 45 potentially relevant full-textarticles were reviewed. After applying all the eligibility criteria, twoRCTs, the EMBRACA and OlympiAD, were included in our NMA.

RESULTS

Ju Wang1, Ye Zhang2, Long Yuan2, Lin Ren2, Yi Zhang2, Xiaowei Qi21Chongqing Municipal Center for Disease Control and Prevention, Chongqing, P.R. China

2 Department of Breast and Thyroid Surgery, Southwest Hospital, Third Military Medical University(Army Medical University), Chongqing, P.R. China

Comparative Efficacy, Safety, and Acceptability of Single-agent Poly (ADP-ribose) Polymerase (PARP) Inhibitors in BRCA-mutated HER2-negative Metastatic or Advanced Breast Cancer: A Network Meta-analysis

This study is registered with PROSPERO(CRD42019138939) and is reported according to thePreferred Reporting Items for Systematic Reviews andMeta-Analyses (PRISMA) extension statement forNMA(16).For this NMA, we searched Web of Science, Embase,PubMed, Medline, ClinicalTrials.gov, the CochraneCentral Register of Controlled Trials, and the WorldHealth Organization (WHO) International ClinicalTrials Registry Platform (ICTRP) from the date ofinception to July 20, 2019, with no languagerestrictions. References derived from full text reviewwere screened to identify potential randomizedcontrolled trials (RCTs) that had not been indexed inthe above databases.We used a prespecified search strategy using termsapplicable to the population of interest. The searchstrategy was designed using a combination of medicalsubject headings (MeSH) and keywords. The MeSHand keywords included “Breast Neoplasm”, “Breastcancer”, “Breast oncology”, “Breast tumor”, “Breastcarcinoma”, “Poly(ADP-ribose) Polymerase Inhibitors”,“Poly(ADP-ribose) Polymerases”, “PARPi”, PARPinames (olaparib, veliparib, niraparib, rucaparib,talazoparib), and synonymous words.

OUTCOMES

The outcomes of interest were efficacy, safety, andacceptability.The primary efficacy outcome of interest wasprogression-free survival (PFS), the primary safetyoutcome of interest was major all-grade and high-grade (grade 3–4) treatment-related adverse events(AEs), and the primary acceptability outcome ofinterest was discontinued treatment due to AEs.The secondary efficacy outcomes included overallsurvival (OS) and objective response rate (ORR). Thesecondary safety outcome was defined as all-gradeand high-grade (grade 3–4) non-hematologic AEs(fatigue, headache); the secondary tolerabilityoutcome was impact on quality of life (QoL).

STATISTICAL ANALYSIS

NMA was carried out using a random-effect modelwithin a Bayesian framework and executed by Rsoftware using the gemtc package (version 3.5.1; RFoundation, Vienna, Austria)(20,21).To determinewhether the results were affected by studycharacteristics, we performed subgroup analyses forprimary efficacy outcomes according to the followingvariables: previous chemotherapy, previous platinum-based therapy, hormone receptor status, and BRCAmutation type. Two-sided P-values of <0.05 wereconsidered statistically significant.

Trials stage

BRCA mutation type HR

Stage of breast cancer

previous chemotherapyregimens

previous cytotoxic regimens

sample sizes(experiment/control

OlympiAD IIIBRCA1/BRCA2

/bothpositive/negative

metastatic breast cancer

no more than two unknown 205/97

EMBRACA III BRCA1/BRCA2positive/negative

metastatic or local advanced breast

cancer unknownno more than

three 287/144

SAFETYF

Tables 1 Randomised controlled trials included in the systematic review and network meta-analysis

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1. Lyons TG, Robson ME. Resurrection of PARP Inhibitors in Breast Cancer. J Natl Compr Canc Netw 2018;16:1150-6.2. Poggio F, Bruzzone M, Ceppi M, et al. Single-agent PARP inhibitors for the treatment of patients with BRCA-mutated HER2-negative metastatic breast cancer: a systematic review and meta-analysis. Esmo Open 2018;3:e000361.

Fig 1. Forest plot comparing PFS for talazoparib, olaparib, and TPC.

Fig 1

Fig 2

Fig 4

Fig 5

Fig 2. Forest plots comparing PFS for talazoparib, olaparib, and TPC (subgroup analysis). (A) Hormone receptor–positive patients; (B) patients with TNBC; (C) patients with prior platinum; (D) patients with no prior platinum; (E) patients with BRCA1 mutation; (F) patients with BRCA2mutation; (G) patients who received no prior chemotherapy.Fig 4. Forest plots comparing any-grade and grade 3–4 hematological AEs. (A) Grade 3–4 anemia; (B) any-grade anemia; (C) grade 3–4 neutropenia; (D) any-grade neutropenia; (E) grade 3–4 decreased white cell count; (F) any-grade decreased white cell count.Fig 5. Forest plots comparing any-grade and grade 3–4 non-hematological/any AEs. (A) Grade 3–4 fatigue; (B) any-grade fatigue; (C) grade 3–4 headache; (D) any-grade headache; (E) grade 3–4 any AEs; (F) any-grade any AEs.Fig 6. Forest plots comparing acceptability of treatment discontinuation and QoL. (A) Treatment discontinuation; (B) QoL.

Fig 3

Fig 3. Forest plots comparing OS and ORR for talazoparib, olaparib, and TPC. (A) OS; (B) ORR.

Fig 1

EFFICACY OUTCOMES

Both talazoparib and olaparib have similar efficacy, safety, and acceptability in patients with BRCA-mutated HER2-negative metastatic or advanced breast cancer. Well-designed head-to-head randomized controlled trials with large samples are suggested to determine the optimal treatment choice.

Fig 6

ACCEPTABILITY

CONCLUSION