Abstract PS10-41: PARP inhibitors for treatment of BRCA positive metastatic breast cancer: A systematic review and meta-analysis

• Published in: Cancer research (Chicago, Ill.) Ill.), 2021-02, Vol.81 (4_Supplement), p.PS10-41-PS10-41
• Main Authors: Kunwor, Ranju, Silver, Daniel P, Bhattacharya, Saveri, Jaslow, Rebecca, Fellin, Frederick, Lopez, Ana Maria, Abu-Khalaf, Maysa M
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.SABCS20-PS10-41

Background: PARP Inhibitors (inh), Olaparib and Talazoparib, are approved for deleterious germline BRCA mutated (gBRCA+) metastatic breast cancer (MBC). This approval was based on a progression-free survival (PFS) benefit seen in two randomized controlled trials (RCTs). Other PARP inh such as Veliparib and Niraparib have also been studied. We conducted this meta-analysis of RCTs aiming to assess PFS and OS of PARP inh in gBRCA+ MBC. Methods: We performed a systematic search for RCTs using Cochrane Library, PubMed, Embase, and Web of Science up to June 2020. Only phase II and III RCTs evaluating PFS for PARP inh alone or in combination with chemotherapy (CT) to standard CT were eligible for this meta-analysis. The pooled analysis of hazard ratio (HR) was performed with RevMan 5.4 software using random effect model. Results: A total of 5 RCTs including 1563 patients were included in this meta-analysis. Baseline study characteristics are listed in Table 1. The pooled HR for PFS was 0.77 (95%CI 0.55-1.09) and the pooled HR for OS was 0.96 (95%CI 0.80-1.16). The only statistically significant adverse event more common in PARP inh group was anemia (Odds Ratio, 3.01; CI95%, 1.14-7.93, P=0.03). (Table 2) Conclusion: The results of our meta-analysis confirmed the previously reported PFS benefit of PARP inh either alone or with standard CT when compared to standard CT alone in gBRCA+ MBC. PARP inh when combined with temozolomide did not show PFS benefit. OS benefit is not seen with PARP inh alone or with standard CT. Ongoing trials are evaluating the benefit of PARP inh in early stage gBRCA+ BC. Table 1: Baseline study characteristics as experimental group vs. control groupVCP: veliparib with carboplatin/paclitaxelVT: veliparib with temozolomidePCP: placebo plus carboplatin/paclitaxelNA: Not available** Subgroup germline BRCA+ pts (n=37, 13 vs 24) is used for PFS and OS analysis in this study.TrialsSample sizeExperimental groupControl groupECOG PS % (0/1/2)Previous CT no. (%)Previous platinum no. (%)Median PFS (mo)Median OS (mo)OlympiAD302 (205 Vs 97)OlaparibStandard CT (Capecitabine or Eribulin orVinorelbine)72.2/28.8/0 Vs 63.9/36.1/0146 (71.2) Vs 69 (71.1)60 (29.3) Vs 26 (26.8)7.0 Vs 4.219.3 Vs 17.1EMBRACA431 (287 Vs 144)TalazoparibStandard therapy53.3/44.3/2.1 Vs 58.3/39.6/1.4176(61.4) Vs 90(62.5)46 (16.0) Vs 30 (20.8)8.6 Vs 5.619.3 Vs 19.5BROCADE284 (97 Vs 99)VCPPCP92/5 Vs 93/623(23.7) Vs 37(37.4)NA14.1 Vs 12.328.3 Vs 25.9(94 Vs 99)VTPCP91/3 Vs 93/628(30.6) Vs 3