Comparison of Neoadjuvant Nab-Paclitaxel+Carboplatin vs Nab-Paclitaxel+Gemcitabine in Triple-Negative Breast Cancer: Randomized WSG-ADAPT-TN Trial Results Better pathologic complete response and relapse-free survival after carboplatin plus paclitaxel compared with epirubicin plus paclitaxel as neoadjuvant chemotherapy for locally advanced triple-negative breast cancer: a randomized phase 2 trial Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial A randomized phase II trial of platinum salts in basal-like breast cancer patients in the neoadjuvant setting. Results from the GEICAM/2006-03, multicenter study Randomized phase II study of weekly paclitaxel with and without carboplatin followed by cyclophosphamide/epirubicin/5-fluorouracil as neoadjuvant chemotherapy for stage II/IIIA breast cancer without HER2 overexpression Anthracyclines in Early Breast Cancer: The ABC Trials-USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG Oncology). 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). Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. TBCRC 001: randomized phase II study of cetuximab in combination with carboplatin in stage IV triple-negative breast cancer. 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.
Background Pathological complete response ( pCR ) is associated with improved prognosis in triple-negative breast cancer ( TNBC ) . The optimal chemotherapy regimen is unclear . Weekly nab-paclitaxel vs conventional paclitaxel or addition of carboplatin to anthracycline-taxane results in higher pCR rates with uncertain survival impact . We evaluated carboplatin vs gemcitabine with a nab-paclitaxel backbone as a short 12-week A-free regimen with a focus on early response . Methods Patients with TNBC ( estrogen receptor/progesterone receptor < 1 % , human epidermal growth factor receptor 2-negative , cT1c-cT4c , cN0/+ ) were r and omly assigned to A : nab-paclitaxel 125 mg/m2/gemcitabine 1000 mg/m2 d1,8 three times weekly ( q3w ) ; vs B : nab-paclitaxel 125 mg/m2/carboplatin AUC2 day 1,8 q3w . The trial was powered for a pCR ( ypT0/is ypN0 ) comparison by therapy arm and early response ( defined as Ki-67 decrease > 30 % or < 500 invasive tumor cells in the three-week serial biopsy ) . All statistical tests were two-sided . Results A total of 336 patients were enrolled ( 48 centers , arms A/B : n = 182/154 ) . The median age was 50 years . At baseline ( A vs B ) , 62.6 % and 62.9 % had cT2 - 4c tumors ; 86.8 % and 90.9 % completed therapy per protocol , respectively . pCR favored arm B ( 28.7 % , 95 % CI = 0.22 to 0.36 , vs 45.9 % , 95 % CI = 0.38 to 0.54 ; 95 % CI(dBA ) = 6.2 % to 27.9 % , P = .002 ) and was lower in nonresponders than in early responders ( 19.5 % vs 44.4 % , P < .001 ) or in patients with unclassifiable early response ( 50.0 % ) . The nab-paclitaxel/gemcitabine was associated with more frequent dose reductions ( 20.6 % vs 11.9 % , P = .04 ) , treatment-related serious adverse events ( 11.1 % vs 5.3 % , P = .07 ) , grade 3 - 4 infections ( 7.2 % vs 2.6 % , P = .07 ) , and grade 3 - 4 ALAT elevations ( 11.7 vs 3.3 % , P = .01 ) . Conclusions This first large r and omized trial suggests high efficacy and excellent tolerability of a neoadjuvant nab-paclitaxel/carboplatin regimen , superior to nab-paclitaxel/gemcitabine in TNBC . De-escalation of further chemotherapy in patients with early pCR after a short anthracycline-free regimen is a promising field of future research . Early necrotic morphological changes and /or proliferation decrease after the first therapy cycle seem to be associated with subsequent pCR Background : No st and ard chemotherapy is used as neoadjuvant therapy in triple negative breast cancer ( TNBC ) . This study has compared carboplatin plus paclitaxel with commonly used epirubicin plus paclitaxel as neoadjuvant chemotherapy ( NAC ) in TNBC . Results : 91 patients with a median age of 47 years ( PC 47 patients , EP 44 patients ) were enrolled . 65 % of the patients were premenopausal . While the objective response rate was similar in the PC and EP arm ( 89.4 % vs. 79.5 % , P = 0.195 ) , the pCR rate in the PC arm was significantly higher ( 38.6 % vs. 14.0 % , P = 0.014 ) . The median follow-up time was 55.0 months . 5-year RFS were 77.6 % and 56.2 % , significantly higher in the PC arm , P = 0.043 . No significant difference in OS was observed between the two arms ( P = 0.350 ) . Adverse events were similar , except for more thrombocytopenia in the PC arm ( P = 0.001 ) . Methods : Patients with stage II/III TNBC were r and omized to receive either paclitaxel ( 175 mg/m2 , day1 ) plus carboplatin ( Area Under the Curve = 5 , day2 ) ( PC ) or epirubicin ( 75mg/m2 , day1 ) plus paclitaxel ( 175 mg/m2 , day2 ) ( EP ) as NAC every three weeks for 4 - 6 cycles . The primary endpoint was rate of pathologic complete response (pCR).The secondary endpoints included relapse-free survival ( RFS ) , overall survival ( OS ) and safety . Conclusions : This study suggested that the addition of carboplatin to paclitaxel was superior to the regimen of epirubicin plus paclitaxel as NAC for TNBC in terms of improving pCR rate and RFS . Further phase 3 study has already started Germline mutations in BRCA1/2 predispose individuals to breast cancer ( termed germline-mutated BRCA1/2 breast cancer , gBRCA-BC ) by impairing homologous recombination ( HR ) and causing genomic instability . HR also repairs DNA lesions caused by platinum agents and PARP inhibitors . Triple-negative breast cancers ( TNBCs ) harbor sub population s with BRCA1/2 mutations , hypothesized to be especially platinum-sensitive . Cancers in putative ‘ BRCAness ’ subgroups — tumors with BRCA1 methylation ; low levels of BRCA1 mRNA ( BRCA1 mRNA-low ) ; or mutational signatures for HR deficiency and those with basal phenotypes — may also be sensitive to platinum . We assessed the efficacy of carboplatin and another mechanistically distinct therapy , docetaxel , in a phase 3 trial in subjects with unselected advanced TNBC . A prespecified protocol enabled biomarker – treatment interaction analyses in gBRCA-BC and BRCAness subgroups . The primary endpoint was objective response rate ( ORR ) . In the unselected population ( 376 subjects ; 188 carboplatin  , 188 docetaxel )  , carboplatin was not more active than docetaxel ( ORR , 31.4 % versus 34.0 % , respectively ; P = 0.66 ) . In contrast , in subjects with gBRCA-BC , carboplatin had double the ORR of docetaxel ( 68 % versus 33 % , respectively ; biomarker , treatment interaction P = 0.01 ) . Such benefit was not observed for subjects with BRCA1 methylation , BRCA1 mRNA-low tumors or a high score in a Myriad HRD assay . Significant interaction between treatment and the basal-like subtype was driven by high docetaxel response in the nonbasal subgroup . We conclude that patients with advanced TNBC benefit from characterization of BRCA1/2 mutations , but not BRCA1 methylation or Myriad HRD analyses , to inform choices on platinum-based chemotherapy . Additionally , gene expression analysis of basal-like cancers may also influence treatment selection .The phase 3 TNT Trial in subjects with triple-negative breast cancer supports the superiority of carboplatin over docetaxel in BRCA1/2-mutated tumors and a greater response to taxanes in the nonbasal subtype Chemotherapy remains as the only systemic treatment option available for basal-like breast cancer ( BC ) patients . Pre clinical models and several phase II studies suggested that platinum salts are active drugs in this BC subtype though there is no r and omized study supporting this hypothesis . This study investigates if the addition of carboplatin to a combination of an alkylating agent together with anthracyclines and taxanes is able to increase the efficacy in the neoadjuvant treatment context . Patients with operable breast cancer and immunophenotypically defined basal-like disease ( ER-/PR-/HER2- and cytokeratin 5/6 + or EGFR+ ) were recruited . Patients were r and omized to receive EC ( epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 for 4 cycles ) followed either by D ( docetaxel 100 mg/m2 × 4 cycles ; EC – D ) or DCb ( docetaxel 75 mg/m2 plus carboplatin AUC 6 × 4 cycles ; EC – DCb ) . The primary end point was pathological complete response ( pCR ) in the breast following the Miller and Payne criteria . Ninety-four patients were r and omized ( 46 EC – D , 48 EC – DCb ) . pCR rate in the breast was seen in 16 patients ( 35 % ) with EC – D and 14 patients ( 30 % ) with EC – DCb ( P value = 0.61 ) . pCR in the breast and axilla was seen in 30 % of patients in both arms . The overall clinical response rate was 70 % ( 95 % CI 56–83 ) in the EC – D arm and 77 % ( 95 % CI 65–87 ) in the EC – DCb arm . Grade 3/4 toxicity was similar in both arms . The addition of carboplatin to conventional chemotherapy with EC – D in basal-like breast cancer patients did not improve the efficacy probably because they had already received an alkylating agent . These findings should be taken into consideration when developing new agents for this disease Abstract Addition of carboplatin to neoadjuvant chemotherapy in HER2-negative breast cancer may improve pathological complete response ( pCR ) rates . We evaluated the efficacy and safety of carboplatin and weekly paclitaxel ( wPTX ) followed by cyclophosphamide , epirubicin , and 5-fluorouracil ( CEF ) as neoadjuvant chemotherapy for HER2-negative breast cancer . Patients with stage II/IIIA HER2-negative breast cancer were r and omly assigned to preoperatively receive CP-CEF ( four 3-week cycles of carboplatin [ area under the curve 5 mg/mL/min , day 1 ] and wPTX [ 80 mg/m2 , day 1 , 8 , 15 ] followed by four 3-week cycles of CEF [ 500/100/500 mg/m2 ] or P-CEF ( four cycles of wPTX followed by four cycles of CEF ) . The primary objective was pCR rate .  Of 181 eligible patients , 89 were r and omly assigned to the  CP-CEF  and 92 to the P-CEF . Two patients in each arm refused to receive neoadjuvant chemotherapy . Overall 88 patients in the CP-CEF and 91 patients in the P-CEF were assessable for efficacy and safety . The pCR rate in the CP-CEF was significantly higher than that in the P-CEF ( 31.8 vs. 17.6 % , one-sided P = 0.01 ) . Among patients with triple-negative breast cancer , the pCR rate in the CP-CEF was significantly higher than that in the P-CEF [ 61.2 ( 23/37 ) vs. 26.3 % ( 10/38 ) , P = 0.003 ] . Grade 3–4 neutropenia was observed in the CP-CEF more frequently than in the P-CEF ( 65.9 vs. 38.5 % ) . Adding carboplatin to neoadjuvant wPTX followed by CEF for HER2-negative breast cancer improved the pCR rate and exacerbated hematotoxicity Purpose Docetaxel and cyclophosphamide ( TC ) was superior to doxorubicin and cyclophosphamide ( AC ) in a trial in early breast cancer . However , activity of TC relative to AC regimens with a taxane ( TaxAC ) is unknown . Methods In a series of three adjuvant trials , women were r and omly assigned to TC for six cycles ( TC6 ) or to a  st and ard TaxAC regimen .  US Oncology Research ( USOR ) 06 - 090 compared TC6 with docetaxel , doxorubicin , and cyclophosphamide ( TAC6 ) . National Surgical Adjuvant Breast and Bowel Project ( NSABP ) B-46-I/USOR 07132 compared TC6 , TAC6 , or TC6 plus bevacizumab . NSABP B-49 compared TC6 with several st and ard AC and taxane combination regimens . Before any analysis of individual trials , a joint efficacy analysis of TC versus the TaxAC regimens was planned , with invasive disease-free survival ( IDFS ) as the primary end point . Patients who received TC6 plus bevacizumab  on NSABP B-46-I/USOR 07132 were not included . A hazard ratio ( HR ) from a stratified Cox model that exceeded 1.18 for TC6 versus TaxAC was predefined as inferiority for TC6 . The prespecified interim monitoring plan was to report for futility if the HR was > 1.18 when 334 IDFS events were observed ( 50 % of 668 events required for definitive analysis ) . Results A total of 2,125 patients were r and omly assigned to receive TC6 regimens and 2,117 patients were r and omly assigned to receive TaxAC regimens . The median follow-up time was 3.3 years . There were 334 IDFS events , and the HR for TC6 versus TaxAC was 1.202 ( 95 % CI , 0.97 to 1.49 ) , which triggered early reporting for futility . The 4-year IDFS was 88.2 % for TC6 and was 90.7 % for TaxAC ( P = .04 ) . Tests for treatment interaction by protocol , hormone receptor status , and nodal status were negative . Conclusion The TaxAC regimens improved IDFS in patients with high-risk human epidermal growth factor receptor 2-negative breast cancer compared with the TC6 regimen PURPOSE One third of patients with triple-negative breast cancer ( TNBC ) achieve pathologic complete response ( pCR ) with st and ard neoadjuvant chemotherapy ( NACT ) . CALGB 40603 ( Alliance ) , a 2 × 2 factorial , open-label , r and omized phase II trial , evaluated the impact of adding carboplatin and /or bevacizumab . PATIENTS AND METHODS Patients ( N = 443 ) with stage II to III TNBC received paclitaxel 80 mg/m(2 ) once per week ( wP ) for 12 weeks , followed by doxorubicin plus cyclophosphamide once every 2 weeks ( ddAC ) for four cycles , and were r and omly assigned to concurrent carboplatin ( area under curve 6 ) once every 3 weeks for four cycles and /or bevacizumab 10 mg/kg once every 2 weeks for nine cycles . Effects of adding these agents on pCR breast ( ypT0/is ) , pCR breast/axilla ( ypT0/isN0 ) , treatment delivery , and toxicities were analyzed . RESULTS Patients assigned to either carboplatin or bevacizumab were less likely to complete wP and ddAC without skipped doses , dose modification , or early discontinuation result ing from toxicity . Grade ≥ 3 neutropenia and thrombocytopenia were more common with carboplatin , as were hypertension , infection , thromboembolic events , bleeding , and postoperative complications with bevacizumab . Employing one-sided P values , addition of either carboplatin ( 60 % v 44 % ; P = .0018 ) or bevacizumab ( 59 % v 48 % ; P = .0089 ) significantly increased pCR breast , whereas only carboplatin ( 54 % v 41 % ; P = .0029 ) significantly raised pCR breast/axilla . More-than-additive interactions between the two agents could not be demonstrated . CONCLUSION In stage II to III TNBC , addition of either carboplatin or bevacizumab to NACT increased pCR rates , but whether this will improve relapse-free or overall survival is unknown . Given results from recently reported adjuvant trials , further investigation of bevacizumab in this setting is unlikely , but the role of carboplatin could be evaluated in definitive studies , ideally limited to biologically defined patient subsets most likely to benefit from this agent PURPOSE The exact definition of pathologic complete response ( pCR ) and its prognostic impact on survival in intrinsic breast cancer subtypes is uncertain . METHODS Tumor response at surgery and its association with long-term outcome of 6,377 patients with primary breast cancer receiving neoadjuvant anthracycline-taxane-based chemotherapy in seven r and omized trials were analyzed . RESULTS Disease-free survival ( DFS ) was significantly superior in patients with no invasive and no in situ residuals in breast or nodes ( n = 955 ) compared with patients with residual ductal carcinoma in situ only ( n = 309 ) , no invasive residuals in breast but involved nodes ( n = 186 ) , only focal-invasive disease in the breast ( n = 478 ) , and gross invasive residual disease ( n = 4,449 ; P < .001 ) . Hazard ratios for DFS comparing patients with or without pCR were lowest when defined as no invasive and no in situ residuals ( 0.446 ) and increased monotonously when in situ residuals ( 0.523 ) , no invasive breast residuals but involved nodes ( 0.623 ) , and focal-invasive disease ( 0.727 ) were included in the definition . pCR was associated with improved DFS in luminal B/human epidermal growth factor receptor 2 ( HER2 ) -negative ( P = .005 ) , HER2-positive/nonluminal ( P < .001 ) , and triple-negative ( P < .001 ) tumors but not in luminal A ( P = .39 ) or luminal B/HER2-positive ( P = .45 ) breast cancer . pCR in HER2-positive ( nonluminal ) and triple-negative tumors was associated with excellent prognosis . CONCLUSION pCR defined as no invasive and no in situ residuals in breast and nodes can best discriminate between patients with favorable and unfavorable outcomes . Patients with noninvasive or focal-invasive residues or involved lymph nodes should not be considered as having achieved pCR . pCR is a suitable surrogate end point for patients with luminal B/HER2-negative , HER2-positive ( nonluminal ) , and triple-negative disease but not for those with luminal B/HER2-positive or luminal A tumors BACKGROUND Pre clinical data suggest that triple-negative breast cancers are sensitive to interstr and crosslinking agents , and that synergy may exist for the combination of a taxane , trastuzumab , and a platinum salt for HER2-positive breast cancer . We therefore aim ed to assess the efficacy of the addition of carboplatin to neoadjuvant therapy for triple-negative and HER2-positive breast cancer . METHODS Patients with previously untreated , non-metastatic , stage II-III , triple-negative breast cancer and HER2-positive breast cancer were enrolled . Patients were treated for 18 weeks with paclitaxel ( 80 mg/m(2 ) once a week ) and non-pegylated liposomal doxorubicin ( 20 mg/m(2 ) once a week ) . Patients with triple-negative breast cancer received simultaneous bevacizumab ( 15 mg/kg intravenously every 3 weeks ) . Patients with HER2-positive disease received simultaneous trastuzumab ( 8 mg/kg initial dose with subsequent doses of 6 mg/kg intravenously every 3 weeks ) and lapatinib ( 750 mg daily ) . Patients were r and omly assigned in a 1:1 ratio with dynamic allocation and minimisation , stratified by biological subtype and Ki-67 level to receive , at the same time as the backbone regimens , either carboplatin ( AUC 1·5 [ 2·0 for the first 329 patients ] once a week ) or no carboplatin . The primary endpoint the proportion of patients who achieved a pathological complete response ( defined as ypT0 ypN0 ) , analysed for all patients who started treatment ; a p value of less than 0·2 was deemed significant for the primary endpoint . This trial is registered with Clinical Trials.gov , number NCT01426880 . FINDINGS 296 patients were r and omly assigned to receive carboplatin and 299 to no additional carboplatin , of whom 295 and 293 started treatment , respectively . In this final analysis , 129 patients ( 43·7 % , 95 % CI 38·1 - 49·4 ) in the carboplatin group achieved a pathological complete response , compared with 108 patients ( 36·9 % , 31·3 - 42·4 ) without carboplatin ( odds ratio 1·33 , 95 % CI 0·96 - 1·85 ; p=0·107 ) . Of the patients with triple-negative breast cancer , 84 ( 53·2 % , 54·4 - 60·9 ) of 158 patients achieved a pathological complete response  with carboplatin , compared with 58 ( 36·9 % , 29·4 - 44·5 ) of 157 without ( p=0·005 ) . Of the patients with HER2-positive tumours , 45 ( 32·8 % , 25·0 - 40·7 ) of 137 patients achieved a pathological complete response with carboplatin compared with 50 ( 36·8 % , 28·7 - 44·9 ) of 136 without ( p=0·581 ; test for interaction p=0·015 ) . Haematological and non-haematological toxic effects that were significantly more common in the carboplatin group than in the no-carboplatin group included grade 3 or 4 neutropenia ( 192 [ 65 % ] vs 79 [ 27 % ] ) , grade 3 or 4 anaemia ( 45 [ 15 % ] vs one [ < 1 % ] ) , grade 3 or 4 thrombocytopenia ( 42 [ 14 % ] vs one [ < 1 % ] ) , and grade 3 or 4 diarrhoea ( 51 [ 17 % ] vs 32 [ 11 % ] ) ; carboplatin was more often associated with dose discontinuations ( 141 [ 48 % ] with carboplatin and 114 [ 39 % ] without carboplatin ; p=0·031 ) . The frequency of grade 3 or 4 haematological events decreased from 82 % ( n=135 ) to 70 % ( n=92 ) and grade 3 or 4 non-haematological events from 78 % ( n=128 ) to 59 % ( n=77 ) in the carboplatin arm when the dose of carboplatin was reduced from AUC 2·0 to 1·5 . INTERPRETATION The addition of neoadjuvant carboplatin to a regimen of a taxane , an anthracycline , and targeted therapy significantly increases the proportion of patients achieving a pathological complete response . This regimen seems to increase responses in patients with triple-negative breast cancer , but not in those with HER2-positive breast cancer . FUNDING GlaxoSmithKline , Roche , and Teva PURPOSE Epidermal growth factor receptor ( EGFR ) is a targetable receptor frequently overexpressed in basal-like breast cancer , which comprises most triple-negative breast cancers ( TNBCs ) , the only subtype without established targeted therapy . PATIENTS AND METHODS In this r and omized phase II trial , patients with metastatic TNBC received anti-EGFR antibody cetuximab ( 400  mg/m(2 ) load then 250 mg/m(2 ) per week intravenously [ IV ] ) alone , with carboplatin ( area under the curve of 2 , once per week IV ) added after progression or as concomitant therapy from the beginning . Response rate ( RR ) was the primary end point ; others included time to progression ( TTP ) , overall survival ( OS ) , and toxicity . Embedded correlative studies included molecular subtyping on archival tissue . Fresh tumor tissue before and after 7 to 14 days of therapy was used for microarray analyses exploring EGFR pathway activity and inhibition . RESULTS In 102 patients with TNBC , RRs were 6 % ( two of 31 ) to cetuximab and 16 % ( four of 25 ) to cetuximab plus carboplatin after progression . RR to those treated from the beginning with cetuximab plus carboplatin was 17 % ( 12 of 71 ) ; 31 % of patients responded or had prolonged disease stabilization . The cetuximab plus carboplatin regimen was well tolerated , but both TTP and OS were short at 2.1 months ( 95 % CI , 1.8 to 5.5 months ) and 10.4 months ( 95 % CI , 7.7 to 13.1 months ) , respectively . Of 73 patients with archival tissue for analysis , 74 % had basal-like molecular subtype . Sixteen patients had tumor biopsies before and 1 week after therapy ; genomic patterns of the EGFR pathway showed activation in 13 and inhibition by therapy in five . CONCLUSION Despite strong pre clinical data , combination cetuximab plus carboplatin in metastatic TNBC produced responses in fewer than 20 % of patients . EGFR pathway analysis showed that most TNBCs involved activation . However , cetuximab blocked expression of the EGFR pathway in only a minority , suggesting that most had alternate mechanisms for pathway activation BACKGROUND Although several r and omised trials in patients with triple-negative breast cancer have shown that the addition of carboplatin , with or without poly(ADP-ribose ) polymerase ( PARP ) inhibitors , to neoadjuvant chemotherapy increases the likelihood of achieving a pathological complete response , the use of these therapies in this setting has remained controversial . The BrighTNess trial was design ed to assess the addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to st and ard neoadjuvant chemotherapy in triple-negative breast cancer . METHODS We did a phase 3 , r and omised , double-blind , placebo-controlled trial ( BrighTNess ) across 145 sites in 15 countries . Patients aged 18 years and older with previously untreated histologically or cytologically confirmed clinical stage II-III triple-negative breast cancer , who were c and i date s for potentially curative surgery and had an Eastern Cooperative Oncology Group performance status of 0 or 1 , were r and omly assigned ( 2:1:1 ) by an interactive response technology system via permuted blocks ( block size of four ) within strata to receive one of three segment 1 regimens : paclitaxel ( 80 mg/m2 intravenously weekly for 12 doses ) plus carboplatin ( area under the curve 6 mg/mL per min , intravenously every 3 weeks , for four cycles ) plus veliparib ( 50 mg orally , twice a day ) ; paclitaxel plus carboplatin plus veliparib placebo ( twice a day ) ; or paclitaxel plus carboplatin placebo ( every 3 weeks for four cycles ) plus veliparib placebo . Following segment 1 , all patients were assigned to segment 2 in which they received doxorubicin and cyclophosphamide every 2 - 3 weeks for four cycles . R and omisation for segment 1 was stratified by germline BRCA mutation status , nodal stage , and planned schedule of doxorubicin and cyclophosphamide administration . The primary endpoint was pathological complete response in breast and lymph nodes as determined by site pathologists following completion of neoadjuvant therapy . Efficacy analyses were done by intention to treat and safety analyses included all patients who received at least one dose of study treatment . These are the first results of an ongoing clinical trial ; the data cutoff for the analyses presented was Dec 8 , 2016 . This study is registered with Clinical Trials.gov , number NCT02032277 . FINDINGS Between April 4 , 2014 , and March 18 , 2016 , 634 patients were r and omly assigned : 316 to paclitaxel plus carboplatin plus veliparib , 160 to paclitaxel plus carboplatin , and 158 to paclitaxel alone . The proportion of patients who achieved a pathological complete response was higher in the paclitaxel , carboplatin , and veliparib group than in patients receiving paclitaxel alone ( 168 [ 53 % ] of 316 patients vs 49 [ 31 % ] of 158 , p<0·0001 ) , but not compared with patients receiving paclitaxel plus carboplatin ( 92 [ 58 % ] of 160 patients , p=0·36 ) . Grade 3 or 4 toxicities , and serious adverse events were more common in patients receiving carboplatin , whereas veliparib did not substantially increase toxicity . The most common grade 3 or 4 events overall were neutropenia ( 352 [ 56 % ] of 628 patients ) , anaemia ( 180 [ 29 % ] ) , and thrombocytopenia ( 75 [ 12 % ] ) through complete treatment , and febrile neutropenia ( 88 [ 15 % ] of 601 patients ) during segment 2 . The most common serious adverse events were febrile neutropenia ( 80 [ 13 % ] of 628 patients ) and anaemia ( 20 [ 3 % ] ) . INTERPRETATION Although the addition of veliparib and carboplatin to paclitaxel followed by doxorubicin and cyclophosphamide improved the proportion of patients with triple-negative breast cancer who achieved a pathological complete response , the addition of veliparib to carboplatin and paclitaxel did not . Increased toxicities with the addition of carboplatin ( with or without veliparib ) to paclitaxel were manageable and did not substantially affect treatment delivery of paclitaxel followed by doxorubicin and cyclophosphamide . Given the consistent results with previous studies , the addition of carboplatin appears to have a favourable risk to benefit profile and might be considered as a potential component of neoadjuvant chemotherapy for patients with high-risk , triple-negative breast cancer . FUNDING AbbVie
Triple negative breast cancer ( TNBC ) represents 15–20 % of breast cancers .
Due to its heterogeneity and high rates of relapse , there is a need to optimize treatment efficacy .
Platinum chemotherapy is still controversial and currently not recommended as first-line treatment for TNBC .
Recent studies have shown promising activity of this regimen .
This study was done to evaluate the effect of platinum chemotherapy on pathologic complete response ( pCR ) after neoadjuvant treatment for early TNBC and progression-free survival ( PFS ) in metastatic TNBC .