Open-label Clinical Trial of Niraparib Combined With Pembrolizumab for Treatment of Advanced or Metastatic Triple-Negative Breast Cancer

e12647 Background: The NeoImmunoboost study (NCT03289819) was designed to evaluate the pathological complete response (pCR) rate and safety of a neoadjuvant combination of the PD-1 antibody pembrolizumab and nab-paclitaxel followed by pembrolizumab with epirubicin and cyclophosphamide in patients with early triple negative breast cancer (TNBC). Methods: This is a prospective, single-arm, multi-center, open-label phase II clinical trial. Female patients with early TNBC were eligible for trial participation. Patients received 12 cycles of weekly nab-paclitaxel intravenous (i.v.) 125 mg/m² body surface area (BSA) in combination with 4 cycles of pembrolizumab i.v. 200 mg q3w; followed by 4 cycles of epirubicin i.v. 90 mg/m² BSA and cyclophosphamide i.v. 600 mg/m² BSA q3w in combination with 4 cycles of pembrolizumab i.v. 200 mg q3w. After 25 patients the protocol was amended, with an initiation boost of 1 cycle of pembrolizumab i.v. 200 mg q3w monotherapy prior to the chemotherapy. Primary trial endpoint was pCR. Secondary endpoints included safety and clinical response rate. Results: Between March 2018 and October 2019, 53 patients were included into the trial. Until now, 47 patients have completed trial treatment and 6 patients are still receiving therapy. 28 patients have received the initiation boost with pembrolizumab, 25 patients did not receive the initiation boost. Up to now, 4 patients terminated the therapy prematurely. Conclusions: pCR data of all patients will be available at the meeting and results of the pCR rates and selected secondary endpoints will be presented at the meeting. Clinical trial information: NCT03289819.

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Efficacy of epirubicin plus cyclophosphamide followed by taxanes versus carboplatin plus taxanes as adjuvant chemotherapy in triple-negative breast cancer: 8.1 years median follow-up on a randomized clinical trial.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.529 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 529-529

Author(s):

Fangchao Zheng ◽

Feng Du ◽

Yongsheng Wang ◽

Xue Wang ◽

Jiayu Wang ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Trial ◽

Triple Negative Breast Cancer ◽

Adjuvant Treatment ◽

Subgroup Analysis ◽

Triple Negative ◽

Brca Mutation ◽

Disease Free Survival ◽

Open Label

529 Background: Four cycles of adjuvant taxanes (paclitaxel or docetaxel) after four cycles of adjuvant doxorubicin plus cyclophosphamide (ECT) are considered a standard adjuvant treatment and improves survival outcomes of triple negative breast cancer (TNBC). The purpose of this analysis was to further assess whether adjuvant carboplatin plus taxanes (TP) was non-inferior to or superior to standard ECT chemotherapy in prolonging the survival time. Methods: This randomized, open-label, multicenter clinical trial conducted at three hospital in China from June, 2009 and October, 2015. Eligible early triple-negative breast cancer (TNBC) patients were randomized (1:1) to receive ECT (four cycles of epirubicin 90 mg/m2 + cyclophosphamide 600 mg/m2 followed by four cycles of docetaxel 75 mg/m2 or paclitaxel 175 mg/m2 every 3 weeks, ECT arm, n = 154) or receive TP (six cycles of docetaxel 75 mg/m2 or paclitaxel 175 mg/m2 + carboplatin AUC 5 every 3 weeks; TP arm, n = 154), which was then followed by surgery. Results: Three hundred and eight patients were recruited in this trial and final date of follow-up was January 20, 2021. Baseline characteristics were balanced between ECT arm and TP arm. Median follow-up was 97.6 months. Median disease free survival (DFS) was not reached; 8-year DFS rate was 78.35% with ECT arm and 81.73% with TP arm (hazard ratio [HR] = 0.84; 95% confidence interval [CI] = 0.50 - 1.40; P = 0.496). Median overall survival (OS) was also not reached; 8-year OS rate was 87.15% with ECT arm and 89.14% with TP arm (HR = 0.87; 95% CI = 0.44 - 1.70; P = 0.676). For TNBC patients with DFS > 4 year, TP arm had a longer DFS than ECT ( P = 0.01), and had a tendency with better OS ( P = 0.4). In this subgroup analysis of SPARC > 50%, TP arm had a longer DFS than ECT ( P < 0.05), and also had a tendency with better OS ( P = 0.06). In subgroup analysis of PD-1 (-) and intravascular invasion (+), TP arm had a better DFS ( P = 0.02) and OS ( P = 0.03) than ECT arm. DFS or OS had no significant differences in ECT and TP arm with BRCA mutation or BRCA wild ( all P values > 0.05). Conclusions: TP chemotherapy showed significant non-inferiority for PFS and OS versus ECT in the first-line adjuvant treatment of early TNBC. For some particular subgroup of TNBC, TP may be a more effective chemotherapy than ECT. TP may be considered an effective alternative to early TNBC. Clinical trial information: NCT01150513.

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Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial

The Lancet Oncology ◽

10.1016/s1470-2045(20)30754-3 ◽

2021 ◽

Vol 22 (4) ◽

pp. 499-511 ◽

Cited By ~ 1

Author(s):

Eric P Winer ◽

Oleg Lipatov ◽

Seock-Ah Im ◽

Anthony Goncalves ◽

Eva Muñoz-Couselo ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Open Label ◽

Phase 3 ◽

Open Label Phase

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Glembatumumab vedotin for patients with metastatic, gpNMB overexpressing, triple-negative breast cancer (“METRIC”): a randomized multicenter study

npj Breast Cancer ◽

10.1038/s41523-021-00244-6 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Linda T. Vahdat ◽

Peter Schmid ◽

Andres Forero-Torres ◽

Kimberly Blackwell ◽

Melinda L. Telli ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Primary Endpoint ◽

Triple Negative ◽

Progression Free Survival ◽

Antibody Drug Conjugate ◽

Open Label ◽

Common Grade ◽

Open Label Phase ◽

Grade 3

AbstractThe METRIC study (NCT#0199733) explored a novel antibody–drug conjugate, glembatumumab vedotin (GV), targeting gpNMB that is overexpressed in ~40% of patients with triple-negative breast cancer (TNBC) and associated with poor prognosis. The study was a randomized, open-label, phase 2b study that evaluated progression-free survival (PFS) of GV compared with capecitabine in gpNMB-overexpressing TNBC. Patients who had previously received anthracycline and taxane-based therapy were randomized 2:1 to receive, GV (1.88 mg/kg IV q21 days) or capecitabine (2500 mg/m2 PO daily d1–14 q21 days). The primary endpoint was RECIST 1.1 PFS per independent, blinded central review. In all, 327 patients were randomized to GV (213 treated) or capecitabine (92 treated). Median PFS was 2.9 months for GV vs. 2.8 months for capecitabine. The most common grade ≥3 toxicities for GV were neutropenia, rash, and leukopenia, and for capecitabine were fatigue, diarrhea, and palmar-plantar erythrodysesthesia. The study did not meet the primary endpoint of improved PFS over capecitabine or demonstrate a relative risk/benefit improvement over capecitabine.

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