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Phase II trial of weekly nab-paclitaxel and carboplatin treatment with or without trastuzumab as nonanthracycline neoadjuvant chemotherapy for locally advanced breast cancer.

ABSTRACT: Neoadjuvant chemotherapy has become standard treatment for women with locally advanced breast cancer. The aim of this study was to compare the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) versus paclitaxel combined with carboplatin.Thirty patients were treated with neoadjuvant nab-paclitaxel (125 mg/m(2), days 1, 8, and 15) and carboplatin (area under the curve =2; days 1, 8, and 15) every 21 days for four cycles. Ninety matched patients received paclitaxel (80 mg/m(2), days 1, 8, and 15) and carboplatin every 21 days for four cycles. Weekly trastuzumab is recommended for overexpression of human epidermal receptor-2. The primary endpoint was pathologic complete response (defined as ypT0/is ypN0). Matching was conducted according to six variables: body mass index, clinical tumor stage, clinical lymph node status, estrogen receptor status, HER2 status, and trastuzumab receiving rate.Ninety percent of patients in the nab-paclitaxel group and 80% of patients in the paclitaxel group experienced a clinical objective response (complete response or partial response; P=0.450). Eight patients in the nab-paclitaxel group and 23 patients in the paclitaxel group had a pathologic complete response in the breast and axillary nodes (26.7% versus 25.6%; P=0.904). Nab-paclitaxel showed a beneficial effective trend on clinical tumor stage II (36.8% versus 15.8%; P=0.051). When trastuzumab was added to nab-paclitaxel, the pathologic complete response rate was not significantly improved more than with trastuzumab and paclitaxel (43.6% versus 39.6%; P=0.769). Carboplatin plus nab-paclitaxel or paclitaxel had similarly low pathologic complete response rates (7.7% versus 10.5%) for the luminal molecular subtype. One (50%) triple-negative patient achieved a pathologic complete response. The nab-paclitaxel regimen caused more grade 4 neutropenia than the paclitaxel regimen (56.7% versus 21.1%; P<0.001).Our study shows that weekly nab-paclitaxel and carboplatin with or without trastuzumab resulted in a pathologic complete response rate that was not superior to the matched cohorts. Future, larger trials are needed to validate that nab-paclitaxel is beneficial for clinical tumor stage II and the triple-negative subgroup.

SUBMITTER: Huang L

PROVIDER: S-EPMC4362893 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Phase II trial of weekly nab-paclitaxel and carboplatin treatment with or without trastuzumab as nonanthracycline neoadjuvant chemotherapy for locally advanced breast cancer.

Huang Liang L Chen Sheng S Yao Ling L Liu Guangyu G Wu Jiong J Shao Zhiming Z

International journal of nanomedicine 20150311

<h4>Background</h4>Neoadjuvant chemotherapy has become standard treatment for women with locally advanced breast cancer. The aim of this study was to compare the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) versus paclitaxel combined with carboplatin.<h4>Methods</h4>Thirty patients were treated with neoadjuvant nab-paclitaxel (125 mg/m(2), days 1, 8, and 15) and carboplatin (area under the curve =2; days 1, 8, and 15) every 21 days for four cycles. Ninety matched ...[more]

PMID: 25792830

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Project description:BackgroundThe anti-tumor activity and acceptable tolerability of pyrotinib plus chemotherapy have been demonstrated in phase III trials in human epidermal growth factor receptor 2-positive metastatic breast cancer (BC). In this study, we assessed the efficacy and safety of neoadjuvant pyrotinib plus trastuzumab and albumin-bound paclitaxel in women with human epidermal growth factor receptor 2-positive early or locally advanced BC.MethodsIn this single-arm exploratory phase II trial, patients with untreated human epidermal growth factor receptor 2-positive BC (stage IIA-IIIC) received pyrotinib 400 mg once daily, trastuzumab 4 mg/kg loading dose, followed by 2 mg/kg once a week, and albumin-bound paclitaxel 125 mg/m2 once a week for four 21-day cycles before surgery. The primary endpoint of the study was total pathological complete response (pCR) rate, defined as no microscopic invasive tumor remnants in the breast and axillary lymph nodes. The secondary endpoints were investigator-assessed objective response rate (ORR) and adverse event profiles.ResultsBetween May 17, 2019 and November 26, 2019, a total of 21 patients were enrolled. The total pCR rate was 57.1% (12/21), whereas 23.8% (5/21) and 19.0% (4/21) of patients had minimal and moderate residual disease (RD), respectively. The ORR reached 100% (21/21) at the end of the neoadjuvant therapy. Grade ≥3 treatment-related adverse events were observed in 42.9% (9/21) of patients, including decreased neutrophil count [7 (33.3%)], diarrhoea [6 (28.6%)], decreased white blood cell count [5 (23.8%)], and vomiting [2 (9.5%)]. Adverse event-related dose reduction and interruption of pyrotinib occurred in 6 (28.6%) and 11 (52.4%) patients, respectively.ConclusionsIn women with human epidermal growth factor receptor 2-positive early or locally advanced BC, neoadjuvant pyrotinib plus trastuzumab and albumin-bound paclitaxel effectively promoted total pCR rate with an acceptable safety profile (ClinicalTrials.gov, NCT04152057).

Project description:BackgroundIn this phase II clinical trial, we evaluated the efficacy of the nonanthracycline combination of carboplatin and nab-paclitaxel in early stage triple-negative breast cancer (TNBC).Patients and methodsPatients with newly diagnosed stage II-III TNBC (n = 69) were treated with neoadjuvant carboplatin (area under the curve 6) every 28 days for four cycles plus nab-paclitaxel (100 mg/m2 ) weekly for 16 weeks. Pathological complete response (pCR) and residual cancer burden (RCB) were analyzed with germline mutation status, tumor-infiltrating lymphocytes (TILs), TNBC molecular subtype, and GeparSixto immune signature (GSIS).ResultsSixty-seven patients were evaluable for safety and response. Fifty-three (79%) patients experienced grade 3/4 adverse events, including grade 3 anemia (43%), neutropenia (39%), leukopenia (15%), thrombocytopenia (12%), fatigue (7%), peripheral neuropathy (7%), neutropenia (16%), and leukopenia (1%). Twenty-four patients (35%) had at least one dose delay, and 50 patients (72%) required dose reduction. Sixty-three (94%) patients completed scheduled treatment. The responses were as follows: 32 of 67 patients (48%) had pCR (RCB 0), 10 of 67 (15%) had RCB I, 19 of 67 (28%) had RCB II, 5 of 67 (7%) had RCB III, and 1 of 67 (2%) progressed and had no surgery. Univariate analysis showed that immune-hot GSIS and DNA repair defect (DRD) were associated with higher pCR with odds ratios of 4.62 (p = .005) and 4.76 (p = .03), respectively, and with RCB 0/I versus RCB II/III with odds ratio 4.80 (p = .01). Immune-hot GSIS was highly correlated with DRD status (p = .03), TIL level (p < .001), and TNBC molecular subtype (p < .001). After adjusting for age, race, stage, and grade, GSIS remained associated with higher pCR and RCB class 0/I versus II/III with odds ratios 7.19 (95% confidence interval [CI], 2.01-25.68; p = .002) and 8.95 (95% CI, 2.09-38.23; p = .003), respectively.ConclusionThe combination of carboplatin and nab-paclitaxel for early stage high-risk TNBC showed manageable toxicity and encouraging antitumor activity. Immune-hot GSIS is associated with higher pCR rate and RCB class 0/1. This study provides an additional rationale for using nonanthracycline platinum-based therapy for future neoadjuvant trials in early stage TNBCs. Clinical trial identification number: NCT01525966 IMPLICATIONS FOR PRACTICE: Platinum is an important neoadjuvant chemotherapy agent for treatment of early stage triple-negative breast cancer (TNBC). In this study, carboplatin and nab-paclitaxel were well tolerated and highly effective in TNBC, resulting in pathological complete response of 48%. In univariate and multivariate analyses adjusting for age, race, tumor stage and grade, "immune-hot" GeparSixto immune signature (GSIS) and DNA repair defect (DRD) were associated with higher pathological complete response (pCR) and residual cancer burden class 0/1. The association of immune-hot GSIS with higher pCR holds promise for de-escalating neoadjuvant chemotherapy for patients with early stage TNBC. Although GSIS is not routinely used in clinic, further development of this immune signature into a clinically applicable assay is indicated.

Dataset Information

Phase II trial of weekly nab-paclitaxel and carboplatin treatment with or without trastuzumab as nonanthracycline neoadjuvant chemotherapy for locally advanced breast cancer.

Publications

Phase II trial of weekly nab-paclitaxel and carboplatin treatment with or without trastuzumab as nonanthracycline neoadjuvant chemotherapy for locally advanced breast cancer.

Similar Datasets

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