Pathologic response and disease-free survival (DFS) after neoadjuvant trastuzumab (T) for HER2+ breast cancer (BC): Results from the National Cancer Institute (NCI) of Mexico.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11533-e11533
Author(s):  
Cynthia Mayte Villarreal-Garza ◽  
Enrique Soto-Perez-de-Celis ◽  
Erika Sifuentes ◽  
Yanin Chavarri Guerra ◽  
Santiago Ruano ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Neoadjuvant Chemotherapy ◽  
Ductal Carcinoma ◽  
Residual Disease ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Rank Test ◽  
Her2 Breast Cancer

e11533 Background: The most accurate definition of pathologic complete response (pCR) in HER2+ BC patients (pts) receiving T-based neoadjuvant chemotherapy associated with improved DFS is controversial, particularly regarding the role of residual ductal carcinoma in situ (ypTis) and focal invasive residuals (ypT1mic). The effect of pCR on DFS in various subgroups of HER2+ BC is also uncertain. Methods: Pts with localized HER2+ BC that received T-based neoadjuvant chemotherapy at NCI between January 2007 and May 2012 were identified. We conducted an exploratory analysis of DFS in pts according to their tumor response. DFS curves were derived from Kaplan-Meier estimates and compared by log-rank test. Multivariate analysis was performed using Cox’s regression model. Results: 243 pts were included for analysis. Median follow-up was 39 months (mo). 49% of pts had no invasive and no in situ residuals at surgery (ypT0), 14.4% had ypTis/ypT1mic residuals and 36.6% had gross residual BC. DFS was significantly superior in pts with both ypT0 and ypTis/ypT1mic (no gross invasive residual BC) compared with those with gross residual disease (60.6 and 62.7 mo respectively vs. 51.6 mo, p=0.011 and 0.017). There was no difference in DFS between ypT0 and ypTis/ypT1mic pts (p=0.402). The rate of no gross invasive residual BC was significantly superior in pts with ER-PR- tumors compared with patients with ER+/PR+ tumors (69.9% vs. 56.7%, p=0.034). No gross invasive residual BC was associated with improved DFS in pts with HER2+ ER-/PR- (60.3 vs. 49.0 mo; p=0.005), as opposed to HER2+ ER+/PR+ tumors (61.0 vs. 51.6 mo; p=0.100). Multivariate analysis showed that tumor size (p=0.013) and no gross invasive residual BC (p=0.13) were associated with improved DFS in all subgroups. Conclusions: The absence of gross invasive residual BC was associated with improved DFS in pts with HER2+ BC treated with T-based neoadjuvant chemotherapy, particularly in those with HER2+ ER-/PR- BC. Our data suggest a comparable DFS in HER2+ BC patients with no gross invasive residual BC regardless of the presence or absence of both ypTis and ypT1mic disease after neoadjuvant treatment.

Long-term outcomes of patients with HER2+ breast cancer with small-size residual disease (≤ypT1) in the absence of pathological response after trastuzumab-based neoadjuvant chemotherapy and without adjuvant T-DM1: A monocentric retrospective study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 589-589
Author(s):  
Ludovic Doucet ◽  
Camille Moreau-Bachelard ◽  
Carole Gourmelon ◽  
Marie Robert ◽  
Dominique Berton ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multivariate Analysis ◽  
Neoadjuvant Chemotherapy ◽  
Residual Disease ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Pathological Response ◽  
Exclusion Criterion ◽  
Excellent Outcome ◽  
Her2 Breast Cancer

589 Background: The Katherine trial has shown that adjuvant T-DM1 improved invasive disease free survival (iDFS) of patients with HER2+ breast cancer who did not achieve a pathological complete response (pCR) with trastuzumab-based neoadjuvant chemotherapy (NAC). However, some subgroups may benefit less from this treatment escalation. Methods: All HER2+ breast cancer patients treated with trastuzumab-based NAC between 2006 and 2016 were retrieved from our institution’s database. Neo- or adjuvant T-DM1 was an exclusion criterion. We then selected the patients who did not achieve a pCR and analyzed the outcome (iDFS and overall survival (OS)) according to ypT, ypN and several factors analyzed in the Katherine trial. Results: Out of the 182 patients, 117 patients reached the inclusion criteria. Patient’s characteristics were similar to the trastuzumab arm of the Katherine trial. With a median follow-up of 75.4 months (29.3–149.7), 28 events (24%) occurred, among which 22 distant relapses. In univariate analysis, ≤ypT1 vs > ypT1, ypN0 vs ypN+, no capsular rupture, signs of histological response (Sataloff not D in T or N) were associated with a better iDFS. In multivariate analysis, only ypT status remained significant. Of note, patients with ≤ypT1 (ypTis, ypT0, ypTmic, ypT1) (n = 81; 69%) had an excellent outcome: 3 years (y) and 5y iDFS rates of 90% (83.6-96.8) and 88.6% (81.9-95.9) respectively. The remaining patients (n = 36; 31%) had a significantly lower 3y and 5y iDFS: 69.2% (55.6-86.2) and 59.5% (45-78.6) respectively (p = 0.0017). OS in a multivariate analysis was also improved in pts with the smaller residual and/or node negative disease (3y OS rates of 100% (100-100) vs 92.1% (85.7-99); 5y OS rates of 96% (90.7-100) vs 81.1% (71.6-91.9); p = 0.02). Conclusions: In the absence of pCR after trastuzumab-based NAC, patients with pathological response scored as ≤ypT1 (ypTis,ypT0, ypTmic, ypT1) have an excellent outcome. These patients may derive less benefit from adjuvant T-DM1.

A pilot chemoprevention study of isopropanolic black cohosh extract in women with ductal carcinoma in situ.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS1609-TPS1609
Author(s):  
Erin Wysong Hofstatter ◽  
Karen Stavris ◽  
Nina Ruth Horowitz ◽  
Brigid K. Killelea ◽  
Theodore Tsangaris ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Sample Size ◽  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Disease Free Survival ◽  
Black Cohosh ◽  
Rank Test

TPS1609 Background: Recent evidence suggests that black cohosh (Cimicifuga racemosa) may be a potential agent for breast cancer prevention. The active ingredients in black cohosh preparations appear to be triterpene glycosides. Recent preclinical data suggest several mechanisms by which triterpenes may prevent and treat breast cancer, including anti-proliferative, pro-apoptotic, anti-estrogenic, and anti-inflammatory effects. Epidemiologic data demonstrate a significant protective effect of black cohosh against the development of breast cancer in healthy women, and prolonged disease-free survival in breast cancer patients. There is also abundant evidence demonstrating the safety and tolerability of black cohosh in several clinical trials studying its use for treatment of hot flashes. We hypothesize that efficacy of black cohosh can be demonstrated in a pilot pre-operative window trial in a cohort of women with ductal carcinoma in situ (DCIS). Methods: In this trial, we treat women with a 2-5 week pre-operative course of commercial standardized isopropanolic black cohosh extract (20 mg orally twice per day). We aim to demonstrate a reduction in breast epithelial cell proliferation as measured by Ki-67 staining in regions of DCIS using traditional IHC staining and AQUA analysis. We also assess safety and tolerability of black cohosh through monitoring of patient adherence, liver function tests and serum hormone levels. 22 patients will be enrolled onto the trial. Sample size is based on power calculations for the specific study aim of determining the mean change in the levels of Ki67, using a targeted effect size. Assuming a 10% drop-out rate, a sample size of 20 patients will achieve 91% power to detect a 0.8 standard deviation of difference with a two-sided significance level at 0.05 using Wilcoxon signed-rank test. Eligible subjects are pre- and post-menopausal women ≥ 18 years of age newly diagnosed with DCIS histologically confirmed on breast core biopsy, prior to definitive excision. Women who have recently taken any agent known to affect Ki67 levels in the breast (e.g. hormone therapy) are excluded. Enrollment is currently ongoing with 10 of 22 patients accrued. Clinical trial registry number NCT01628536. Clinical trial information: NCT01628536.

Randomized Parallel Study of Doxorubicin Plus Paclitaxel and Doxorubicin Plus Cyclophosphamide As Neoadjuvant Treatment of Patients With Breast Cancer

2004 ◽  
Vol 22 (24) ◽  
pp. 4958-4965 ◽  
Author(s):  
Véronique Diéras ◽  
Pierre Fumoleau ◽  
Gilles Romieu ◽  
Michèle Tubiana-Hulin ◽  
Moïse Namer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Complete Response ◽  
Conservative Surgery ◽  
Axillary Lymph Nodes ◽  
Axillary Lymph ◽  
Cancer Management

Purpose This randomized, noncomparative, parallel-group study was designed to evaluate the pathologic complete response (pCR) rate of combined doxorubicin plus paclitaxel (AP) and doxorubicin plus cyclophosphamide (AC) as neoadjuvant chemotherapy in patients with previously untreated breast cancer who were unsuitable for conservative surgery. Patients and Methods A total of 200 patients with T2-3, N0-1, M0 disease were randomly assigned in a 2:1 ratio to receive preoperative chemotherapy with either doxorubicin 60 mg/m2 plus paclitaxel 200 mg/m2 as a 3-hour infusion (AP) or doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 (AC) every 3 weeks for 4 courses followed by surgery. Results A pCR (eradication of invasive carcinoma in tumor and in axillary lymph nodes) was found in 16% and 10% of patients in the AP and AC arms, respectively, by study center pathologists, and in 8% and 6% of patients, respectively, by independent pathologists. Patients with pCRs tended to have unifocal disease, tumors with negative hormonal receptor status, and less differentiation (Scarff, Bloom, and Richardson scale grade 3). Breast-conserving surgery was performed in 58% and 45% of patients in the AP and AC arms, respectively. An objective clinical response was achieved in 89% of patients in the AP arm and 70% in the AC arm. At a median follow-up of 31 months, disease-free survival (DFS) was higher in patients who reached pCR versus those without pCR (91% v 70%). Conclusion The encouraging pathologic and clinical responses of patients with breast cancer after neoadjuvant chemotherapy with doxorubicin plus paclitaxel warrant additional investigation of paclitaxel in the neoadjuvant setting of breast cancer management.

Predictive factors for pathologic complete response (pCR) to trastuzumab (T)-based neoadjuvant chemotherapy in HER2+ breast cancer (BC) women treated in the National Cancer Institute (NCI) of Mexico.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 634-634
Author(s):  
Erika Sifuentes ◽  
Yanin Chavarri Guerra ◽  
F. Berenice Baez-Revueltas ◽  
Enrique Soto-Perez-de-Celis ◽  
Fernando Lara-Medina ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Tumor Size ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Complete Response ◽  
Chi Square ◽  
Chemotherapy Sensitivity ◽  
Axillary Nodes ◽  
Her2 Breast Cancer ◽  
Chi Square Test

634 Background: Neoadjuvant treatment identifies subgroups of patients (pts) with different prognosis. In HER2+ BC, some tumors have been reported to be more sensitive to anti-HER2 therapy than others. We conducted an exploratory analysis in HER2+ BC women who received T-based neoadjuvant chemotherapy. Methods: Clinico-pathologic data from HER2+ BC pts who received neoadjuvant chemotherapy and T between January 2007 and May 2012 at the NCI were identified. Estrogen receptor (ER), progesterone receptor (PR) and HER2 expression were determined by immunohistochemistry and/or FISH. pCR was defined as complete absence of invasive tumor in breast and axillary nodes. Proportion differences were tested using the Chi-square test. A generalized linear model was used for multivariate analysis. Results: 243 pts received T-based neoadjuvant chemotherapy for localized HER2+ BC tumors. Median age was 49 (26-72) years. 96% had positive axillary nodes at diagnosis and median tumor size was 5.5 (1.5-20) cm. 49.4% had hormone receptor (HR) + (ER+ and/or PR+) and 50.6% HR negative (ER- and PR-) tumors. 63.4% pts achieved pCR. HR negative tumors reached significantly higher pCR rates than HR + tumors (69.9% vs. 56.7%, p=0.034). Pts with inflammatory BC (n=27) had a trend to achieve pCR less frequently than the non-inflammatory tumors (48.1% vs. 65.3%). Those who received taxane-anthracyline sequence chemotherapy (n=20) achieved pCR in 70% of the cases vs. 62.8% with anthracycline-taxane sequence. Differences among other variables (age, tumor size, nodes and HER2 positivity ++/+++) were not significant. Variables that positively influenced pCR were HR negative status (p=0.015), non-inflammatory BC (p=0.082) and chemotherapy sequence (p=0.086). Conclusions: HR negative HER2+ BC tumors were associated with higher pCR, consistent with neoadjuvant trial reports. Preclinical data suggest bi-directional crosstalk between HER2 and ER pathways, which might influence anti-HER2 agents and chemotherapy sensitivity for tumors co-expressing both receptors. New strategies are needed to overcome resistance for HER2+ HR+ BC tumors.

Evaluation of TOP2A and TIMP-1 as predictive markers of pathologic complete response to neoadjuvant anthracycline-based chemotherapy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11503-e11503
Author(s):  
Joyce Maria L. Maia ◽  
Elizabeth Santana Santos ◽  
Rafael Costa Lessa ◽  
Felipe D'Almeida Costa ◽  
Stephania Bezerra ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Predictive Biomarker ◽  
Complete Response ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Her2 Breast Cancer ◽  
Pre Treatment

e11503 Background: Factors predictive of response to anthracyclines can help selecting patients who really benefit from its use. HER2 amplification, TOP2A aberrations, and changes in tissue inhibitor of metalloproteinase (TIMP-1) expression in breast carcinomas have been shown to be associated with incremental benefit from anthracycline chemotherapy. Methods: We retrospectively analyzed data on the outcome of patients undergoing neoadjuvant anthracycline-based chemotherapy. Evaluated nuclear TOP2A protein expression and cytoplasmatic TIMP-1 expression in tumor cells in breast cancer biopsies by immunohistochemistry (IHC) and reviewed the pathological responses after completion of neoadjuvant treatment. Results: From 2002 to 2012, data from 97 patients was reviewed. Sixty four patients had the paraffin blocks corresponding to the pre-treatment biopsy to analysis the TOP2A and forty nine to TIMP-1. Patients were considered positive for TOP2A if the level of expression in IHC was higher than 20% and graduated TIMP-1 as weak, moderate or strong expression. Thirty percent of the patients achieved pathologic complete response (pCR) in pos-treatment surgical specimens. There was an association between TOP2A IHC expression and tumor pathological complete response (pCR) with higher pCR in TOPO2A positive tumors (pCR 44% vs 14%; p=0.008). There was no association between TIMP-1 expression and pCR. A moderate or strong TIMP-1 expression was associated with higher disease-free survival in multivariate analysis (p=0,005). No difference in PFS and OS was observed between patients with pCR after a median follow-up of 36 months. Conclusions: The expression of TOP2A seems to be a promising predictive biomarker of pCR to antracycline-based neoadjuvant chemotherapy in HER2 breast cancer. The predictive value and form of assessment of TIMP-1 remain uncertain. These findings should be better evaluated in prospective neoadjuvant trials.

scholarly journals Randomized phase II study comparing the efficacy and safety of SOX versus mFOLFOX6 as neoadjuvant chemotherapy without radiotherapy for locally advanced rectal cancer (KSCC1301)

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Keisuke Miwa ◽  
Eiji Oki ◽  
Masanobu Enomoto ◽  
Keisuke Ihara ◽  
Koji Ando ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Completion Rate ◽  
Rank Test ◽  
Current Standard

Abstract Background Preoperative chemoradiotherapy (CRT), the current standard of care for locally advanced rectal cancer (LARC), is associated with many radiotherapy (RT)-related side effects. We aimed to evaluate whether S-1 and oxaliplatin (SOX) or folinic acid, 5-FU, and oxaliplatin (mFOLFOX6) can be as effective as neoadjuvant chemotherapy (NAC) regimens for LARC without RT. Methods Patients with untreated resectable LARC were randomly assigned to receive SOX or mFOLFOX6. The NAC protocol period was 3 months. The primary endpoint was 3-year disease-free survival (DFS), and the secondary endpoints included pathological effects, surgical completion rate, 3-year survival, and safety. Results From September 2013 to October 2015, 56 and 54 patients were enrolled in the SOX and mFOLFOX6 arms, respectively. The 3-year DFS rates were 69.4% (95% confidence interval [CI] 54.9–83.6) and 73.4% (95% CI 58.7–83.6) in the SOX and mFOLFOX6 arms, respectively; no significant differences were found between the arms (log-rank test; P = 0.5315, hazard ratio: 0.808, 95% CI 0.414–1.578). The 3-year survival rates were 92.3 and 91.8% in the SOX and mFOLFOX6 arms, respectively. The surgical completion rate was 98.1% overall, 100% in the SOX arm, and 96.0% in the mFOLFOX6 arm. The incidences of pathological response rates ≥grade 1b were 41.5 and 43.8% in the SOX and mFOLFOX6 arms, respectively. Both treatments were manageable and tolerable. Conclusion We demonstrated the effectiveness and safety of SOX and mFOLFOX6, both of which may be new neoadjuvant treatment candidates in previously untreated LARC cases. Trial registration Date of enrolment of the first participant to the trial: 3rd Oct 2013; This study was registered in the UMIN clinical trials registry on 14th Aug, 2013. (Prospectively registered, UMIN-CTR number UMIN000011486). https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&recptno=R000013441&language=J

Comparative efficacy of neoadjuvant to adjuvant chemotherapy for the treatment of early-stage HER2 negative breast cancer: A population-based analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12100-e12100
Author(s):  
Nathalie LeVasseur ◽  
Christine E. Simmons ◽  
Lovedeep Gondara ◽  
Caroline Speers ◽  
Rekha M. Diocee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Neoadjuvant Chemotherapy ◽  
Residual Disease ◽  
Early Stage ◽  
Tumour Size ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Population Based ◽  
Comparative Efficacy

e12100 Background: The use of neoadjuvant treatment has increased over the past decade due to its ability to assess tumour sensitivity to systemic treatment in vivo, and to downstage women for increased breast conserving surgery. Recent studies have stratified patients with residual disease to receive additional treatment, which has resulted in meaningful improvements in survival. However, meta-analysis data suggest similar long-term outcomes for patients treated with neoadjuvant chemotherapy (NACT) compared to adjuvant chemotherapy (ACT) in historical randomized trials. The comparative efficacy in a real-world setting utilizing modern chemotherapy regimens is unknown. Methods: A retrospective review of the BC Cancer Breast Cancer Outcomes Unit (BCOU) was performed to identify patients with stage I-III HER-2 negative breast cancer treated with chemotherapy at the BC Cancer Agency from 2005-2010. Patients were then divided into 2 groups: those who received neoadjuvant chemotherapy (NACT) and those who received adjuvant chemotherapy (ACT). A matched analysis (age, stage, subtype) for patients treated with NACT vs ACT (matched 1:3) was then performed using a propensity scoring method to compare distant disease-free survival (DDFS), breast cancer specific survival (BCSS) and overall survival (OS). No patients received adjuvant chemotherapy for residual disease after NACT. Results: A total of 656 patients met the inclusion criteria, consisting of 164 NACT and 492 ACT cases. Median age was 49 years (37-68) in the NACT group vs 49 (37-65) in the ACT group (p = 0.71). The majority had stage 3 disease, 64% in both groups (p = 1.0). Most were hormone receptor positive (HR+), 67.1% vs 70.7% in the NACT vs ACT groups, respectively (p = 0.41). 5-year DDFS was 75% with NACT (95%CI 67, 82) and 77% with ACT (95%CI 72, 81), p = 0.87. 5-year OS for patients treated with NACT was 77% (95%CI 71, 84) and 80% (95%CI 75, 85) for patients treated with ACT, p = 0.33. 5-year BCSS was 80% with NACT (95% CI 70, 86) and 82% (95%CI 77, 86) with ACT, p = 0.75. Multivariate analysis for tumour size, nodal involvement and subtype are ongoing. Conclusions: The use of NACT compared to ACT in a population-based setting did not result in significant differences in DDFS, OS or BCSS. Acknowledging the comparative efficacy of these approaches will be informative to determine if the addition of subsequent adjuvant treatment for patients with residual disease after NACT will lead to differential benefits in a population-based setting.

Translesion synthesis genes POLI and REV1 in breast tumors and response to neoadjuvant chemotherapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12642-e12642
Author(s):  
Patricia Thompson ◽  
Emma V Jones ◽  
Christina Preece ◽  
Jinyu Li ◽  
Jigna Bhalla ◽  
...  
Keyword(s):  
Dna Damage ◽  
Neoadjuvant Chemotherapy ◽  
Residual Disease ◽  
Pathologic Complete Response ◽  
Translesion Synthesis ◽  
Small Sample ◽  
Breast Cancers ◽  
Tumor Subtype ◽  
Expression Levels ◽  
Her2 Breast Cancer

e12642 Background: Translesion synthesis (TLS) of DNA by specialized polymerases (POLs) and REV1, a scaffold protein that recruits other TLS DNA POLs for nascent strand extension, experimentally enable tumor cells to replicate through DNA damage. TLS POLs are hypothesized to contribute to treatment resistance. Methods: We conducted a discovery gene expression study using NanoString technology with a bespoke codeset enriched for DNA damage response genes and RNA from 12 TN, 10 HER2+ and 29 ER+/HER2- breast cancer patients before neoadjuvant chemotherapy (NACT) and when available, in the matching residual tumor. Eleven patients achieved a pathologic complete response (pCR), 12 had < 1 cm residual disease (partial responders) and 28 patients had > 1cm residual disease (non-responders). RNA counts were normalized and log-transformed for differential expression analyses corrected for false discovery. Results: DNA polymerase Iota ( POLI) was the top overexpressed gene in the pretreatment biopsy of non-responders independent of tumor subtype (p corrected = 0.0002). Expression of REV1 was also significantly higher in non-responders and positively correlated with POLI (r = 0.577, p < 0.0001). Despite a small sample size, pretreatment expression levels of POLI and REV1 were significantly higher in ER+ (n = 38) than ER- (n = 13) tumors (p = 0.0006). When restricted to ER+ tumors, POL1 and REV1 expression levels were significantly higher in pretreatment biopsy of non-responders (n = 25) than partial and complete responders (n = 13). For ER+ patients, response by median POL1/REV1 expression levels are shown in Table. Pre/post treatment POL1 and REV1 expression did not change in patients with residual disease. Conclusions: In discovery, two genes involved in TLS of DNA (POLI and REV1) were found overexpressed in pretreatment biopsies from breast cancers poorly responsive to NACT, independent of tumor subtype. Overexpression was more common among ER+ tumors, which exhibit a high inherent resistance to chemotherapy. If confirmed, expressed levels of POLI and REV1 may identify a subgroup of breast cancers resistant to NACT for which targeted inhibition of mutagenic TLS may be beneficial. [Table: see text]

Randomized, phase II trial to evaluate the efficacy and safety of atezolizumab plus capecitabine adjuvant therapy compared to capecitabine monotherapy for triple receptor-negative breast cancer (TNBC) with residual invasive cancer after neoadjuvant chemotherapy (MIRINAE trial, KCSG-BR18-21).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS597-TPS597
Author(s):  
In Hae Park ◽  
Gun Min Kim ◽  
Jee Hyun Kim ◽  
Hanjo Kim ◽  
Kyong Hwa Park ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Phase Ii ◽  
Residual Disease ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Invasive Disease ◽  
Free Survival ◽  
Disease Free

TPS597 Background: Triple negative breast cancer (TNBC), lack of ER, PR and HER2 expression, is known to have aggressive clinical features such as early recurrence, drug resistance, and frequent distant metastasis at the diagnosis. The most effective chemotherapy combinations used for early TNBC include anthracycline, taxanes, and/or platinum agents. Achieving a pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) provides important prognostic information and is considered as a surrogate endpoint in many clinical trials especially with TNBC. Patients with residual invasive disease after NAC have a high risk for early relapse and worse prognosis compared to those with pCR. Therefore, patients who did not get pCR could be better candidates for additional adjuvant treatment because their risk of recurrence would be higher than those with pCR. The CREATE-X (capecitabine for residual cancer as adjuvant therapy) trial howed that adjuvant capecitabine treatment improved 5-yr rate of disease free survival in TNBC subtype. A recent study indicated that immunosuppressive microenvironment had developed even in early stage of TNBC with increased T cells with a high exhaustion signature which are targets of immune modulating agents. Therefore, earlier cooperation of immune modulating drugs would be beneficial by generating a long-lasting anti-tumor immune response to micrometastatic disease, thus preventing disease relapse or recurrence. Methods: This study is a phase II, multicenter, randomized open label trial of atezolizumab (anti-PD-L1 antibody) and capecitabine compared with capecitabine in patients with TNBC who had residual disease after NAC. 284 patients will be enrolled from 15 sites in Korea with a primary objective to access the 5-yr invasive disease-free survival (IDFS) rate. Secondary objectives include 5-yr IDFS rate in PD-L1 positive population, distant relapse free survival (DRFS), overall survival (OS), and safety. Major inclusion and exclusion criteria are followings; 1) histologically confirmed TNBC, 2) received anthracycline and taxane based NAC followed by complete breast surgery, 3) residual disease after NAC must be ≥1cm in the greatest dimension, and/or have macroscopically positive lymph nodes. The study is open with 13 patients enrolled at the time of submission. Clinical trial information: NCT03756298 .

scholarly journals Randomized Phase II Study Comparing the Efficacy and Safety of SOX versus mFOLFOX6 as Neoadjuvant Chemotherapy without Radiotherapy for Locally Advanced Rectal Cancer (KSCC1301)

2020 ◽  
Author(s):  
Keisuke Miwa ◽  
Eiji Oki ◽  
Masanobu Enomoto ◽  
Keisuke Ihara ◽  
Koji Ando ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Completion Rate ◽  
Rank Test ◽  
Current Standard

Abstract BackgroundPreoperative chemoradiotherapy (CRT), the current standard of care for locally advanced rectal cancer (LARC), is associated with many radiotherapy (RT)-related side effects. We aimed to evaluate whether S-1 and oxaliplatin (SOX) or folinic acid, 5-FU, and oxaliplatin (mFOLFOX6) can be as effective as neoadjuvant chemotherapy (NAC) regimens for LARC without RT. MethodsPatients with untreated resectable LARC were randomly assigned to receive SOX or mFOLFOX6. The NAC protocol period was 3 months. The primary endpoint was 3-year disease-free survival (DFS), and the secondary endpoints included pathological effects, surgical completion rate, 3-year survival, and safety.ResultsFrom September 2013 to October 2015, 56 and 54 patients were enrolled in the SOX and mFOLFOX6 arms, respectively. The 3-year DFS rates were 69.4% (95% confidence interval [CI] 54.9–83.6) and 73.4% (95% CI 58.7–83.6) in the SOX and mFOLFOX6 arms, respectively; no significant differences were found between the arms (log-rank test; P = 0.5315, hazard ratio: 0.808, 95% CI 0.414–1.578). The 3-year survival rates were 92.3% and 91.8% in the SOX and mFOLFOX6 arms, respectively. The surgical completion rate was 98.1% overall, 100% in the SOX arm, and 96.0% in the mFOLFOX6 arm. The incidences of pathological response rates ≥grade 1b were 41.5% and 43.8% in the SOX and mFOLFOX6 arms, respectively. Both treatments were manageable and tolerable. ConclusionWe demonstrated the effectiveness and safety of SOX and mFOLFOX6, both of which may be new neoadjuvant treatment candidates in previously untreated LARC cases.Trial registrationThis study was registered in the UMIN clinical trials registry on Aug 14th, 2013. (UMIN-CTR number UMIN000011486). https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&recptno=R000013441&language=J

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