Table 5 Combination treatment for TNBC

NCT00080301, NCT00082433

III

Ixabepilone + capecitabine vs. capecitabine alone

443

Locally advanced or m TNBC

PFS: 4.2 vs. 1.7 m; OS: 9.0 vs. 10.4 m; RR: 31 vs. 15%

[22]

PrECOG 0105

II

Iniparib, gemcitabine and carboplatin

80

Early-stage TNBC and BRCA1/2 mutation-associated BC

pCR:36%

[25]

GeparSixto; GBG 66

II

Paclitaxel, doxorubicin, and bevacizumab with or without carboplatin

315

Untreated, nonmetastatic, stage II-III, TNBC and HER2⁺ BC

pCR: 53.2 vs 36.9%

[26]

GeparSixto

II

As above

291

As above

pCR in ITT: 56.8 vs. 41.4%; pCR in germline BRCA mutations: 65.4 vs. 66.7%; pCR in non-BRCA mutation: 55 vs. 36.4%; DFS in non-BRCA mutation: 85.3 vs. 73.5 m

[27]

NCT01216111

III

Paclitaxel + carboplatin vs. cyclophosphamide + epirubicin + fluorouracil + docetaxel

647

Operable TNBC after definitive surgery

DFS: 86.5 vs. 80.3%

[28]

CALGB 40,603 (Alliance)

III

Paclitaxel + doxorubicin + cyclophosphamide + carboplatin and/or bevacizumab

443

Stage II to III TNBC

Carboplatin with pCR breast: 60 vs. 44%; Bevacizumab with pCR breast 59 vs. 48%; Carboplatin with pCR breast/axilla: 54 vs. 41%

[29]

ChiCTR-TRC-14005019

II

Docetaxel, epirubicin with or without lobaplatin

125

Operable stage I to III TNBC

pCR breast: 93.5 vs. 73.0%

[30]

CBCSG006

III

Cisplatin plus gemcitabine vs paclitaxel plus gemcitabine

236

Untreated mTNBC

PFS: 7.73 vs. 6.47 m

[31]

I-SPY 2 TRIAL

II

Veliparib with carboplatin

72

stage II or III HER2⁻ BC

pCR: 51 vs. 26%

[34]

BrighTNess

III

Veliparib + carboplatin + paclitaxel vs. carboplatin + paclitaxel vs. paclitaxel

634

Stage II-III TNBC

pCR: 53.1 vs. 57.5 vs. 31.0%

[35]

NCT01837095

I

Eribulin and balixafortide

56

HER2⁻ mBC

PR: 30%

[86]

UCBG 12–1

II

Abiraterone acetate plus prednisone

34

AR⁺ metastatic or inoperable locally TNBC

CBR: 20.0%

[42]

NCT02971761

II

Enobosarm and pembrolizumab

16

AR⁺ mTNBC

CR: 6.3%; PR: 6.3%; SD: 12.5

[43]

BELLE-4

II/III

Paclitaxel with buparlisib or placebo

416

HER⁻ locally advanced or mBC without prior chemotherapy

PFS: 8.0 vs. 9.2 m; PFS in PI3K pathway-activated population: 9.1 vs. 9.2 m

[49]

LOTUS

II

Paclitaxel with ipatasertib or placebo

124

untreated inoperable, locally advanced or mTNBC

PFS: 6.2 vs. 4.9 m; PFS in PTEN-low: 6.2 vs. 3.7 m

[53]

FAIRLANE

II

Ipatasertib plus paclitaxel or placebo

151

Early TNBC

pCR: 17% vs. 13%; pCR with PTEN-low: 16% vs. 13%; pCR with altered PIK3CA/AKT1/PTEN 18% vs.12%

[54]

PAKT

II

Paclitaxel with capivasertib or placebo

140

Untreated m TNBC

PFS: 5.9 vs. 4.2 m;

PFS with PIK3CA/AKT1/PTEN-altered: 9.3 vs. 3.7 m; OS: 19.1 vs. 12.6 m

[55]

NCT01931163

II

Everolimus plus cisplatin

22

Stage II/III TNB

RR: 22.7%

[56]

GeparQuinto

III

Anthracycline and taxane-containing chemotherapy, with or without bevacizumab

493

TNBC

Overall pCR: BRCA1/2 mutant 50%, no BRCA mutant 31.5%;

Bevacizumab: BRCA1/2 mutant 61.5%, no BRCA mutant 35.6%

[64]

NCT03394287

II

Camrelizumab with continuous apatinib or intermittent apatinib

40

Advanced TNBC within three lines of systemic therapy

PFS: 3.7 vs. 1.9 m; objective RR: 43.3 vs. 0.0%; DCR: 63.3 vs. 40.0%

[66]

NCT02657889

II

Niraparib and pembrolizumab

47

advanced or metastatic TNBC

PFS: 8.3 m; ORR: 21.3%; objective RR in BRCA mutation: 46.6%

[36]

IMpassion130

III

Nab-paclitaxel plus atezolizumab or placebo

451

Untreated mTNBC

PFS: 7.2 vs. 5.5 m; PFS in PD-L1⁺: 7.5 vs. 5.0 m;

OS: 21.3 vs. 17.6%; OS in PD-L1⁺: 25.0 vs. 15.5%

[134]

IMpassion131

III

Atezolizumab-paclitaxel

651

Untreated advanced TNBC

PFS in ITT: 5.7 vs. 5.6 m; PFS with PD-L1⁺: 6.0 vs. 5.7 m; OS in ITT: 14.2 vs. 14.5%; OS with PD-L1⁺: 15.2 vs. 15.8%; overall RR in ITT: 54 vs. 47%; overall RR with PD-L1⁺: 63 vs. 55%

[135]

IMpassion031

III

Nab-paclitaxel with atezolizumab or placebo

455

Untreated stage II-III TNBC

pCR in ITT: 57.6 vs. 41.1%; pCR with PD-L1⁺: 68.8 vs. 49.3%

[136]

KEYNOTE-355

III

Pembrolizumab + chemotherapy vs. placebo + chemotherapy

847

untreated locally recurrent inoperable or mTNBC

PFS in ITT: 7.5 vs. 5.6 m; PFS in CPS of 1 or more: 9.7 vs. 5.6 m

[137]

KEYNOTE-522

III

Pembrolizumab + paclitaxel + carboplatin vs. placebo + paclitaxel + carboplatin

602

untreated stage II or stage III TNBC

pCR: 64.8 vs. 51.2%

[138]