Phase II trial of nivolumab with chemotherapy as neoadjuvant treatment in inflammatory breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS604-TPS604
Author(s):  
Maryann J. Kwa ◽  
Nancy Tray ◽  
Francisco J. Esteva ◽  
Yelena Novik ◽  
James L. Speyer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Phase Ii ◽  
Inflammatory Breast Cancer ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Primary Study ◽  
Immune Gene ◽  
Study Objective ◽  
Systemic Spread

TPS604 Background: Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer with poor prognosis and is often resistant to neoadjuvant chemotherapy with risk of early recurrence and systemic spread of disease. PD-L1 expression in IBC is frequent (Bertucci et al. Oncotarget 2015), and blockade of the PD-1/PD-L1 axis with checkpoint inhibitors has emerged as a promising treatment to enhance anti-tumor immunity and clinical response. We hypothesize that PD-1 blockade with nivolumab in combination with neoadjuvant (primary) chemotherapy will increase the rate of pathologic complete response (pCR) and reduce risk of recurrence in patients with IBC. Methods: This is a single-arm open-label multicenter phase II study of nivolumab with neoadjuvant chemotherapy in patients with non-metastatic IBC (n = 52) (ClinicalTrials.gov: NCT03742986). All breast cancer subtypes (based on ER/PR/HER2) will be allowed. Patients will receive nivolumab 360 mg IV on day 1 (21-day cycle) for four cycles in addition to standard chemotherapy. Cohort 1 (patients with triple negative breast cancer or hormone receptor-positive (HR)/HER2-negative IBC) will receive nivolumab in combination with paclitaxel followed by doxorubicin and cyclophosphamide (AC). Cohort 2 (patients with HER2-positive IBC) will receive nivolumab in combination with a taxane (docetaxel or paclitaxel), trastuzumab, and pertuzumab followed by AC. All patients will then undergo mastectomy followed by radiation. The primary study objective is pCR rate (ypT0/Tis ypN0). Secondary objectives will be safety, tolerability and invasive recurrence-free interval. Association of correlative biomarkers with pCR and sensitivity or resistance to therapy with the combination of nivolumab and chemotherapy will be evaluated. Analyses will include mutational and neoantigen load, tumor-infiltrating lymphocytes (TILs) by histopathological assessment, T-cell receptor (TCR) by immunosequencing, and immune gene profiles in the tumor. PD-L1 expression in tumor tissue is not required for enrollment but will be assessed as a predictive marker. Clinical trial information: NCT03742986.

Anlotinib plus chemotherapy as neoadjuvant treatment of high-risk, early-stage triple-negative breast cancer: A prospective, single-arm, single-center, phase II clinical study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12585-e12585
Author(s):  
Xi Chen ◽  
Shuqun Zhang ◽  
Xuexin Li ◽  
Yinbin Zhang ◽  
Youhuai Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Neoadjuvant Chemotherapy ◽  
Phase Ii ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Early Stage ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Pathological Stage

e12585 Background: Anlotinib is an oral multi-targeted tyrosine kinase inhibitor (TKI) that strongly inhibits VEGFR, PDGFR, FGFR, and c-kit. Combining anti-angiogenesis with chemotherapy yielded increased response rates in patients with early-stage triple-negative breast cancer (TNBC). This phase II study aims to evaluate the efficacy and safety of adding anlotinib to standard neoadjuvant chemotherapy in primary TNBC. Methods: Patients aged 18 years or older with previously untreated stage ⅡB-IIIA histologically documented TNBC were assigned to receive chemotherapy plus oral Anlotinib (12 mg qd, d1-14; 21 days per cycle; total 8 cycles). Chemotherapy comprised of epirubicin at 90 mg/m2 and cyclophosphamide at 600 mg/m2 followed by docetaxel at 100 mg/m2, (21 days per cycle; both total 4 cycles), which was then followed by surgery. The primary endpoint was pathologic complete response (pCR) (no invasive carcinoma in breast or axilla). Stratification was based on the clinical breast cancer stage. This study is registered on Chinese Clinical Trials.gov (ChiCTR2000038174), and still ongoing. Results: Between July 2019 to June 2020, 18 patients (female) with pathological stage ⅡB (83.3%), and IIIA (16.7%) were enrolled with a median age of 46 years (range: 32-72). Overall pCR rate was 44.4% (8/18, CI 95%: 24.6%-66.3%). The pCR rate of pathological stage IIB patients was 46.7%(CI 95%: 26.7%-69.9%), which is tend to be better than the pCR rate of 33.3%(CI 95%: 6.2%-79.2%) for patients with pathological stage IIIA. There are 21 kind of AEs were observed, all including 56 times grade 1 AEs and 34 times grade 2 AEs, no grade 3 or higher AE was observed. The most common AEs included hand-foot syndrome(55.6% in total with 33.3% grade 2 and 22.2% grade 1), oral mucositis(50.00% in total with 33.3% grade 2 and 16.67% grade 1), fatigue(61.1%, all grade 1), hoarse voice(33.3%, all grade 1), nasal bleeding(27.8%, all grade 1), hypertension(22.2% with 5.6% grade 2) and diarrhea(22.2% with 5.6% grade 2). Neither unexpected safety signals nor treatment-related death occurred. Conclusions: The addition of anlotinib to neoadjuvant chemotherapy showed manageable toxicity and promising antitumor activity for patients with high-risk, early-stage TNBC. Clinical trial information: ChiCTR2000038174.

Gemcitabine plus paclitaxel and gemcitabine plus docetaxel in first- or second-line metastatic breast cancer: A phase II randomized trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1046-1046 ◽  
Author(s):  
R. V. Boccia ◽  
L. Vaughn ◽  
H. Zeigler ◽  
Y. Wang ◽  
J. Gill ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Primary Study ◽  
Similar Response ◽  
Study Objective ◽  
Study Results ◽  
Combination Regimens

1046 Background: The combination of gemcitabine (G) with paclitaxel (P) has proven efficacy in the first-line treatment of metastatic breast cancer (MBC). In addition, the combination of G with docetaxel (D) has shown activity in several nonrandomized, Phase II, MBC trials. This randomized Phase II trial was conducted to assess the efficacy and safety of G plus P and G plus D combination regimens in previously treated patients with MBC. Methods: Patients with locally advanced or metastatic breast cancer were randomized equally into two groups to receive either GP (G 1,250 mg/m2 IV on Days 1 and 8 plus P 175 mg/m2 IV on Day 1) or GD (G 1,000 mg/m2 IV on Days 1 and 8 plus D 75 mg/m2 IV on Day 1). Treatment was administered every 21 days and continued until disease progression or undue toxicity. Planned enrollment was 112 patients (56 per group). The primary study objective was tumor response assessed using RECIST criteria. Toxicities were assessed using the NCI Common Toxicity Criteria, Version 2.0. Results: Twenty-five patients were enrolled in each treatment group and accrual was stopped due to slow enrollment. In the GP group, only 23 patients were evaluable for response and 24 patients were monitored for safety. One patient did not receive study medication and was not assessed for efficacy or safety. A second patient was determined to have nonmeasurable disease at baseline and was not assessed for response. Overall response rate was 39% (95% CI 20, 61) for the GP group and 40% (95% CI 21, 61) for the GD group. The median number of cycles administered was 6.5 in the GP group and 6.0 in the GD group. Detailed study results are summarized in the table below. Conclusions: These results show that GP and GD combination regimens are both efficacious in the treatment of MBC, with similar response rates and manageable toxicity profiles. [Table: see text] No significant financial relationships to disclose.

Phase II study of panitumumab, nab-paclitaxel, and carboplatin followed by FEC neoadjuvant chemotherapy for patients with primary HER2-negative inflammatory breast cancer.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 1087-1087 ◽  
Author(s):  
Naoko Matsuda ◽  
Xiaoping Wang ◽  
Savitri Krishnamurthy ◽  
Ricardo H. Alvarez ◽  
Jie S. Willey ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Phase Ii ◽  
Inflammatory Breast Cancer ◽  
Phase Ii Study

Locoregional recurrence following pathologic complete response in patients with T1-3 N0 breast cancer treated with neoadjuvant chemotherapy, breast conserving surgery and whole breast radiation: Is a trial of omission of radiation warranted?

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12625-e12625
Author(s):  
Elena Parvez ◽  
Thierry Muanza
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Endocrine Therapy ◽  
Locoregional Recurrence ◽  
Prospective Trial ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Breast Conserving Surgery ◽  
Study Objective

e12625 Background: Pathologic complete response(pCR) after neoadjuvant chemotherapy(NAC) in patients with breast cancer(BC) is associated with decreased recurrence and improved survival. In NSABP B18 and B27, 10-yr locoregional recurrence(LRR) after pCR in patients with Stage I-III BC undergoing breast conserving surgery(BCS) and whole breast RT(WBRT) was 5.2-6.9%. However, LRR may be overestimated as Her2 therapy was not used and only some eligible patients received endocrine therapy. A retrospective study using modern protocols found a 5-yr LRR of up to 2.6%. We hypothesize that LRR in N0 patients is even lower, and de-escalation of therapy should be examined. The study objective is to assess if a prospective trial of omission of WBRT after BCS in patients with N0 BC and pCR after NAC is warranted and to assess feasibility. Methods: Patients with T1-T3 N0 invasive BC diagnosed between Dec 2011-2017 treated with NAC and BCS were identified from a hospital BC registry. Health records were retrospectively reviewed to identify patients with pCR, defined as absence of residual invasive or in-situ disease(ypT0N0). Incidents of locoregional and distant recurrence were recorded. Results: Of 89 patients with T1-3 N0 invasive BC treated with NAC and BCS, 29(32.6%) had pCR. Median follow-up was 61.1 months. Median age was 55 yrs and median tumour size was 2.4cm. Receptor status was 16(55.2%) HR-Her2-, 4(13.8%) HR-Her2+, 7(24.1%) HR+Her2+ and 2(6.9%) HR+Her2-. NAC protocols consisted of an anthracycline and/or a taxane in 27(90%) patients, and 6 patients were treated on NAC trials. All patients with Her2+ disease received Her2 targeted therapy. Adjuvant endocrine therapy was taken by 8 of 9 patients with HR+ disease. All patients received WBRT without nodal RT. RT plan was available for 26(86.7%) patients. RT dose ranged from 40-50Gy, and all but 4 received tumour bed boost. There were no local or regional recurrence events at last follow-up. One patient developed brain metastases at 15.7 months. Conclusions: Over 6 years, 29 patients were identified that would be eligible for a prospective trial evaluating omission of WBRT after pCR in N0 patients treated with NAC and BCS. At median 5-yr follow-up, there were no locoregional recurrences in our cohort, demonstrating that the absolute benefit provided by WBRT is likely small. Our results indicate a prospective trial is warranted and will require multi-institution participation to accrue.

Pathologic Complete Response With Six Compared With Three Cycles of Neoadjuvant Epirubicin Plus Docetaxel and Granulocyte Colony-Stimulating Factor in Operable Breast Cancer: Results of ABCSG-14

2007 ◽  
Vol 25 (15) ◽  
pp. 2012-2018 ◽  
Author(s):  
Günther G. Steger ◽  
Arik Galid ◽  
Michael Gnant ◽  
Brigitte Mlineritsch ◽  
Alois Lang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Complete Response ◽  
Breast Conserving Surgery ◽  
Operable Breast Cancer ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Stimulating Factor

Purpose Preoperative (neoadjuvant) chemotherapy for operable breast cancer downstages tumors initially not suitable for breast-conserving surgery. A pathologic complete response (pCR) to neoadjuvant chemotherapy may be a surrogate for longer overall survival, but this beneficial effect remains to be established. This phase III trial evaluated whether doubling the number of cycles of neoadjuvant treatment increased the pCR rate. Patients and Methods Patients with biopsy-proven breast cancer (T1-4a-c, N±, M0; stage I to III) were eligible and randomly assigned to either three or six cycles of epirubicin 75 mg/m2 and docetaxel 75 mg/m2 on day 1 and granulocyte colony-stimulating factor on days 3 through 10 (ED+G), every 21 days. The primary end point was the pCR rate of the breast tumor. Secondary end points were pathologic nodal status after surgery and the rate of breast-conserving surgery. Results A total of 292 patients were accrued, and 288 patients were assessable for efficacy and safety. Groups were well balanced for known prognostic factors. Six cycles of ED+G, compared with three cycles, resulted in a significantly higher pCR rate (18.6% v 7.7%, respectively; P = .0045), a higher percentage of patients with negative axillary status (56.6% v 42.8%, respectively; P = .02), and a trend towards more breast-conserving surgery (75.9% v 66.9%, respectively; P = .10). Rates of adverse events were similar, and no patients died on treatment. Conclusion Doubling the number of neoadjuvant ED+G cycles from three to six results in higher rates of pCR and negative axillary nodal status with no excess of adverse effects. Thus, six cycles of ED+G should be the standard neoadjuvant treatment for operable breast cancer if this combination is chosen.

A phase II study of neoadjuvant docetaxel/carboplatin with or without trastuzumab in locally advanced breast cancer: Response and cardiotoxicity

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10515-10515 ◽  
Author(s):  
H. R. Chang ◽  
D. Slamon ◽  
R. Prati ◽  
J. Glaspy ◽  
M. D. Pegram ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Phase Ii ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Advanced Breast ◽  
Cardiac Symptoms ◽  
Her 2

10515 Background: A phase II clinical trial was conducted to study the safety and efficacy of neoadjuvant docetaxel/carboplatin (T/C) with or without trastuzumab (H) in women with stage III breast cancer. Methods: Forty-eight of 75 planned primary breast cancer patients (T3 or T4, any N, M0), age between 18 and 80 have been enrolled. Four cycles of T (75 mg/m2) + C (AUC 6) were given every 3 weeks preoperatively. Patients with HER-2 amplified tumors (FISH +) were randomized to receive either weekly concurrent H or T/C alone preoperatively and T/C plus H postoperatively. Tumors were assessed clinically at baseline and after neoadjuvant therapy. Cardiac assessment consisted of medical history, EKG and LVEF (by echocardiogram or MUGA) at baseline and at the end of neoadjuvant chemotherapy. Results: Available data from 45 of 48 enrolled patients showed 49% (22 cases) with complete clinical response, with 54.5% being HER-2 (+) (12 cases). Stable disease was seen in one patient who was HER-2 (−) (2.2%). Of 37 with complete pathology verification, 11 (29.7%) showed pathologic complete response (pCR) of the primary tumor with 5 cases being HER-2 (+). Of the 22 HER-2 (+) cases that completed neoadjuvant treatment, 11 received T/C/H and 11 received T/C. pCR was noted in 36.4% of the T/C/H group and 9% of the T/C group. LVEF data is available from 43 patients during the neoadjuvant phase, showing 18.6% (8 cases) with decrease of ≥ 10% (5 patients in the T/C arm and 3 patients in the T/C/H arm), although none had cardiac symptoms or LVEF below the normal limit. Conclusions: T/C ± H is clinically active in patients with locally advanced breast cancer including a 30% pCR rate. The cardiotoxicity rates were comparable between patients who received T/C and T/C/H. No significant financial relationships to disclose.

Preliminary results of a phase II study of neoadjuvant treatment with docetaxel (T), doxorubicin (A) and capecitabine (X) in locally advanced or inflammatory breast cancer (LABC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10678-10678
Author(s):  
G. Perez Manga ◽  
M. Méndez ◽  
M. I. Palomero ◽  
R. Quibén ◽  
J. Belón
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Inflammatory Breast Cancer ◽  
Combined Treatment ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Additional Patient ◽  
High Survival ◽  
Toxicity Profile ◽  
Ecog Ps

10678 Background: Previous studies suggest that combined treatment of chemotherapy + surgery + radiotherapy has a high survival rate in pts with locally advanced or inflammatory breast cancer. Primary objective was evaluate response rate. Secondary objectives were time to progression and toxicity profile of neoadjuvant chemotherapy T, A and X in pts with LABC. Methods: Eligibility criteria: Pts with histological confirmation of LABC, ECOG PS ≤ 2, age ≤ 75 years, LVEF > 50%, and adequate bone marrow, renal and hepatic function. Prior systemic therapy, surgery or radiotherapy for breast cancer was not allowed. Pts with invasive bilateral breast cancer were not included. Treatment: T (30 mg/m2) iv day 1, 8 and 15, A (50 mg/m2) iv day 1 and X (1500 mg/m2 o.d.) days 1–14, in a 4 weeks course. This scheme was repeated up to 4 cycles followed by surgery. According to investigator criteria pts receive a maximum of six cycles. Radiotherapy and hormonal treatment are allowed depending on molecular markers. Expression of markers was performed by inmunohistochemistry before chemotherapy. Results: 36 pts were included in this analysis, with a median age of 48 years (25–69). ECOG PS was 0 in 32% of pts and 1 in 68%. Hormonal receptor status was ER+ 43%, PR+ 34% and C-erb2+ 52%. A total of 131 cycles (median 4, range 1–4) were administered. Median relative dose intensity was 86% for T, 91% for A and 93% for X. Two patients are still undergoing treatment; of 34 evaluable pts for efficacy, 11 achieved CR, 22 PR and 1 PD resulting in an ORR of 97% (CI 95%: 92–100). Surgery was performed in 34 pts: 3 (9%) of them achieved pathological CR and one additional patient had non invasive carcinoma. Grade III/IV toxicity per patient was neutropenia (69%), leucopenia (53%), febrile neutropenia (8%), mucositis (14%), diarrhea (11%), nausea/vomiting (6%), dysgeusia (3%) and asthenia (3%). Median follow up time was 8.8 months. Conclusions: T, A and X every 28 days administered during 4 cycles as neoadjuvant chemotherapy in LABC is an active regimen with a manageable toxicity profile before surgery. No significant financial relationships to disclose.

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