Neoadjuvant Chemotherapy Regimen Research Articles

Biomarker analysis to predict the pathological response to neoadjuvant chemotherapy in locally advanced gastric cancer: An exploratory biomarker study of COMPASS, a randomized phase II trial.

Background: The findings of COMPASS, a randomized phase II study, suggested that the regimens and courses of neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer (GC) did not affect the pathological response. However, pathological complete response was achieved in 10% patients who received four courses of either S-1/cisplatin or paclitaxel/cisplatin. We hypothesized that if relevant biomarkers could be used to predict the suitable NAC regimen before treatment initiation, further improvements could be ensured in the outcomes of locally advanced GC.Materials and Methods: mRNA extraction, real-time polymerase chain reaction, and immunohistochemical analyses were performed using endoscopic biopsy specimens of primary tumors, collected prior to NAC, to determine the clinically relevant biomarkers.Results: TIMP1, DSG2, RRM1, MUC2, EGFR, ZDHHC14, and CLDN18.2 were identified as biomarker candidates, since their expression was significantly associated with the pathological responses to each NAC regimen. Furthermore, TIMP1 and DSG2 were identified as predictive biomarkers of the pathological response to each NAC regimen.Conclusions: The effective prediction of the pathological response to NAC regimens in locally advanced GC using biomarkers identified from endoscopic biopsy specimens indicates the possibility of personalizing NAC based on biomarker analysis.

Evaluation of PD-L1, tumor-infiltrating lymphocytes, and CD8+ and FOXP3+ immune cells in HER2-positive breast cancer treated with neoadjuvant therapies.

The tumor immune microenvironment plays a critical role in the prognosis and outcome of breast cancers. This study examined the role of tumor-infiltrating lymphocytes (TILs), CD8+, FOXP3+ lymphocytes, PD-L1 expression, and other clinicopathological parameters in HER2+ breast cancer and correlate with tumor response to neoadjuvant therapy. We included 173 HER2+ patients treated with neoadjuvant HER2-targeted chemotherapy regimens from 2010 to 2016. 67 cases had biopsy blocks to evaluate TIL, CD8, FOXP3, and PD-L1 immunohistochemistry staining. Tumors were classified as pCR vs non-pCR group. Clinicopathological parameters, TIL, CD8+ and FOXP3+ cell count, and PD-L1 expression were correlated with pCR rate. Univariate analyses showed that pCR rate was significantly correlated with low PR, low ER, high Ki-67, high FOXP3, HER2 IHC3+ , high HER2 ratio and copy number. By multivariate analysis, Ki-67 was the only variable significantly correlated with pCR. PD-L1 expression was detected in 9.2% cases. TIL hotspot has a non-significant correlation with pCR rate (p = 0.096). High Ki-67 is a strong predictor for pCR in HER2+ breast cancer. TIL and FOXP3 T cells may play a role in tumor response in HER2+ cancer. PD-L1 is expressed in a subset of HER2+ breast cancer, supporting a role of immunotherapy in treating a subset of HER2+ breast cancers. The role of PD-L1, TIL, and other markers of immunogenicity as predictors of response to neoadjuvant chemotherapy in HER2+ breast cancer should be further evaluated.

Comprehensive comparison of clinicopathological characteristics, treatment, and prognosis of borderline resectable pancreatic cancer according to tumor location

BackgroundThe prognosis of borderline resectable (BR) pancreatic cancer (PC) has improved by multidisciplinary therapy. However, the differences in clinical course between pancreatic head (Ph) and pancreatic body and tail (Pbt) cancer has not been fully elucidated. Therefore, we conducted this study to compare the clinical course of BR PC patients according to tumor location. MethodsWe retrospectively investigated consecutive patients with BR PC who initiated neoadjuvant chemotherapy (NAC) between March 2015 and April 2019. We compared clinicopathological characteristics, treatment, recurrence pattern and post recurrence treatment between Ph and Pbt cancer patients. We also compared recurrence free survival (RFS) and overall survival (OS) according to tumor location. ResultsA total of 108 patients with BR PC were included. Tumor location was Ph 74 and Pbt 34, respectively. Initial regimen of NAC was nab-paclitaxel/gemcitabine in 106 and gemcitabine in 2, respectively. Although Pbt location was associated with more advanced T stage, it showed similar N stage, pathological stage, RFS, OS, and details of adjuvant chemotherapy compared to Ph location. The most common site of postoperative recurrence was liver-only recurrence in Ph tumor (32% vs. 6%, p = 0.04) and peritoneal dissemination-only recurrence in Pbt tumor (35% vs. 11%, p = 0.06). Furthermore, Ph cancer patients received a higher rate of monotherapy compared to Pbt cancer patients (19% vs. 0%, p = 0.08). ConclusionsIn our experience tumor location was not a prognostic factor for OS in BR PC. Postoperative recurrence pattern and treatment after recurrence were different according to tumor location.

The UPMC Hillman Cancer Center Approach to the Management of Colorectal Cancer During the COVID-19 Pandemic Era

The UPMC Hillman Cancer Center Approach to the Management of Colorectal Cancer During the COVID-19 Pandemic Era

Comparison of Docetaxel + Oxaliplatin + S-1 vs Oxalipatin + S-1 as Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer: A Propensity Score Matched Analysis.

BackgroundWhat is the optimal neoadjuvant chemotherapy (NAC) regimen for locally advanced gastric cancer (LAGC) remains debatable. The objective of this study was to compare the efficacy of docetaxel+oxaliplatin+S-1 (DOS) vs oxaliplatin+S-1 (SOX) as NAC for LAGC.MethodsData of 248 LAGC patients who received either DOS or SOX as NAC in our hospital between January 2010 and January 2018 were reviewed retrospectively. Propensity score matched (PSM) analysis was applied to minimize the selection bias in both groups. Prognostic factors were screened by univariate and multivariate Cox regression analyses.ResultsOf the 248 LAGC patients included, 180 patients were subjected to the PSM analysis. Patients in DOS group showed a better tumor response to NAC, higher radical resection rate and R0 resection rate than those in SOX group. The overall survival (OS) rate in DOS group was better than that in SOX group, although the overall incidence of Grade 3/4 NAC-related toxicity in DOS group was higher, as represented by leukopenia and neutropenia. Multivariate analysis revealed that the NAC regimen, cTNM stage and the R0 resection rate were independent prognostic factors. In addition, patients with TLND less than 16 population showed a worse OS rate. Subgroup analysis indicated that patients benefited from the addition of docetaxel regardless of the clinical T stage, but those with high clinical N stages (N2-3) did not.ConclusionDOS is a safe and feasible NAC regimen for LAGC, which is worth popularizing in clinical practice.

Evaluation of breast surgical oncology complications after single agent versus dual agent HER2 targeted neoadjuvant chemotherapy

BackgroundThe aim of this study was to determine whether differing neoadjuvant chemotherapy (NAC) regimens for HER2 positive breast cancer (HER2+ BC) are associated with differing surgical complications. Our goal was to evaluate postoperative complications in HER2+ BC patients receiving NAC with Herceptin (trastuzumab, H) alone versus in combination with pertuzumab (HP). MethodsRetrospective chart review was performed of patients with Stage I-III HER2+ BC receiving NAC from 2007 to 2016. Demographics, tumor characteristics, surgical procedure, and 60-day postoperative complications were analyzed. ResultsH (n = 101) and HP (n = 132) were similar with respect to tumor characteristics and surgical procedure. Overall operative complications were similar between groups (p = 0.63), as were major versus minor complications (p = 1.0). Subgroup analysis identified a higher rate of complications for lumpectomy patients receiving HP versus H (p = 0.003). ConclusionsNeoadjuvant chemotherapy with HP is associated with increased complications after lumpectomy. Additional studies are warranted to assess causative factors for this observation.

Controlling lymph node micrometastases by neoadjuvant chemotherapy affects the prognosis in advanced esophageal squamous cell carcinoma.

The purpose of this study is to determine the clinical significance of micrometastases after neoadjuvant chemotherapy (NAC) and the difference in controlling micrometastases using different NAC regimens in resectable advanced esophageal squamous cell carcinoma (ESCC). We analyzed patients with ESCC who underwent esophagectomy with lymph node dissection after NAC with Adriamycin + cisplatin + 5-fluorouracil (ACF) or docetaxel + cisplatin + 5-fluorouracil (DCF). Micrometastasis was defined as a single isolated cancer cell or cluster of cancer cells on the cervical, recurrent nerve, or abdominal LNs as shown by immunohistochemical staining with anti-cytokeratin antibody (AE1/AE3). The associations between micrometastases, recurrence, prognosis, and regimen differences were investigated. One hundred and one cases (ACF group: 51 cases; DCF group: 50 cases) were analyzed. Micrometastases occurred in 24 patients (23.8%): 17/51 (33.3%) in the ACF group and 7/50 (13.5%) in the DCF group (p = 0.0403). The 5-year recurrence-free survival (RFS) rates for patients without (n = 77) and with (n = 24) micrometastases were 62 and 32%, respectively, (hazard ratio, 2.158; 95% confidence interval, 1.170-3.980; stratified log-rank test, p = 0.0115). A multivariate analysis showed that stage pN1 or higher and micrometastases were significant risk factors affecting RFS. In resectable advanced ESCC, controlling micrometastases in the LNs after NAC varied by regimen and may be associated with preventing ESCC recurrence.

Density and distribution of lymphocytes in pretherapeutic rectal cancer and response to neoadjuvant therapy.

BackgroundLymphocytic density in rectal cancer has been reported to be associated with therapeutic response, but the role of the lymphocytic distribution pattern remains to be determined. This study aimed to evaluate the association between the distribution and density of lymphocytes in rectal-cancer tissue with tumor response to neoadjuvant therapy.MethodsWe retrospectively analysed 134 patients with rectal cancer receiving neoadjuvant therapy within a prospectively maintained cohort. Pretherapeutic biopsy samples were stained with immunohistochemistry (CD4 and CD8). Densities of intratumoral periglandular lymphocytes (IPLs) and tumor-infiltrating lymphocytes (TILs) were assessed separately. Logistic-regression analysis was used to assess associations of lymphocyte densities with tumor regression grade (TRG), controlling for clinicopathological, molecular, and regimen features.ResultsCompared with cases in the lowest quartile of CD8+ TILs, those in the highest quartile were significantly associated with better TRG (multivariate odds ratio, 0.23; 95% confidence interval, 0.07 to 0.76; P < 0.001). In contrast, CD8+ IPLs, CD4+ IPLs, and CD4+ TILs were not significantly associated with TRG (P = 0.033, 0.156, and 0.170, respectively). Sensitivity analyses detected no interaction between CD8+ TILs and regimen of neoadjuvant radiation (Pinteraction = 0.831) or chemotherapy (Pinteraction = 0.879) on TRG.ConclusionsOur data suggest that CD8+ TILs, but not IPLs, are independently associated with response to neoadjuvant therapy, regardless of the regimen of radiation or chemotherapy.

Regimens of neo-adjuvant chemotherapy in the treatment of breast cancer: A systematic review & network meta-analysis with PRISMA-NMA compliance.

Efficacy of neo-adjuvant therapy depends on the used regimens. There are contradictory findings regarding relative efficacy of these regimens. Accordingly, present study assessed the relative efficacy of Anthracyclines, Taxanes and added targeted therapies in neo-adjuvant setting simultaneously with a focus on tumor response and breast conserving surgery among breast cancer patients. The network meta-analysis model was used. Ranking of treatment was done by surface under cumulative ranking curve for each regimen. Out of 1286 screened records obtained by searching PubMed and Cochrane register of controlled trials, a total of 34 studies randomizing 12,630 breast cancer patients were included. Network meta-analysis for pathological complete response (pCR) revealed Addition of targeted therapies especially Trastuzumab for HER2+ breast cancer and Bevacizumab for HER2- breast cancer along with Anthracyclines and/or Taxanes based chemotherapy significantly improves pCR but with increased haematological toxicities. All the regimens performed similar in terms of breast conserving surgery rates.

In vitro drug sensitivity (IDS) of patient-derived primary osteosarcoma cells as an early predictor of the clinical outcomes of osteosarcoma patients.

Early prediction of clinical response to conventional chemotherapy is a significant factor in determining an overall treatment strategy for osteosarcoma. Cells were extracted from treatment-naïve biopsies from 16 osteosarcoma patients who received a doxorubicin and cisplatin-based neoadjuvant chemotherapy regimen and their sensitivities to doxorubicin and cisplatin were measured as IC50 values. Associations of in vitro drug sensitivity (IDS) levels and clinical outcomes were examined. Primary osteosarcoma cells responded to doxorubicin and cisplatin with IC50 values of 0.088 ± 0.032µM and 16.7 ± 8.5µM, respectively. The patients with a non-metastatic phenotype and surviving patients showed significantly lower IC50 values for both drugs. ROC analysis defined the optimal IC50 cut-off values for doxorubicin (IDSdox) and cisplatin (IDScpt) as 0.05µM (AUC 0.82) and 14µM (AUC 0.87), respectively. Survival analysis found significantly longer disease-free survival (DFS, n = 14) and overall survival (OS, n = 16) times in the patients with low IDSdox (p = 0.0064 for DFS and p = 0.0102 for OS) and low IDScpt (p = 0.0204 for DFS and p = 0.0021 for OS). Interestingly, when the patients with low IDScpt and those with low IDSdox were combined (Group 1), significant associations with prolonged DFS (p = 0.0042, C-statistic 0.78) and OS (p = 0.0010, C-statistic 0.79) were found. In this cohort, histological response to neoadjuvant chemotherapy could predict only OS. This study indicates that IDS analysis could potentially be a practical, rapid, and reliable technique for predicting clinical outcomes. It could also be used to identify patients for whom conventional chemotherapy is most appropriate and, in the future, help advance personalized therapy.

Efficacy and safety of neoadjuvant chemotherapy (NACT) with paclitaxel plus carboplatin and oral metronomic chemotherapy (OMCT) in patients with technically unresectable oral cavity squamous cell carcinoma (SCC).

e18550 Background: NACT regimen for patients with oral cavity scc is based on maximum tolerated doses (MTD). Combination of MTD and metronomic chemotherapy schedule will lead to initial debulking of tumor and subsequent inhibition of angiogenesis, this may produce synergistic effect and overcome the drug resistance of MTD schedule. We assessed the efficacy and safety of this combination as NACT in patients with technically unresectable oral cavity SCC. Methods: This is retrospective analysis of prospectively maintained data. Fourteen patients having technically unresectable oral cavity SCC received NACT with paclitaxel (175mg/m2) plus carboplatin (AUC5) 3 weekly (MTD schedule) and OMCT (methotrexate 9mg/m2 once a week, celecoxib 200mg twice daily and erlotinib 150mg once daily). Patient were assessed clinically and radiologically after minimum of two cycles for resectability. Radiological response was evaluated as per RECIST 1.1. We report response rate, resectability and tolerance of this NACT regimen. Results: Median age of the patients was 38 years. Twelve patients (85%) were male. Twelve (85%) and two (15%) patients had buccal mucosa and oral tongue primary respectively. AJCC 2017 stage IVA and IVB disease was present in 85% and 15% patients respectively. Reason for technical unresectabilty was skin edema above zygoma in five (36%), high infratemporal fossa involvement in five (36%), nodal encasement of major vessels in two (14%) and posterior extent of oral tongue tumor into oropharynx in two (14%) patients. Median number of NACT administered were three. The tumor of nine (64%) patients showed partial response and none of the patients had tumor progression. Tumor of nine patients (64%) were deemed resectable after NACT. Common grade 3/4 toxicities (CTCAE 5.0) were neutropenia in eight (57%), thrombocytopenia in three (21%), febrile neutropenia, hypokalemia and diarrhoea in two patients (14%) each. Conclusions: Paclitaxel and carboplatin along with OMCT is well tolerated and easily administered NACT regimen with high response rate and resectabilty in patients with technically unresectable oral cavity SCC.

Dissecting outcomes of patients (pts) with &lt;ypT2N0 disease after neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer (MIBC): Results from a large, international, multicenter collaboration.

5043 Background: Pathologic complete response (pCR) after NAC for MIBC is strongly correlated with long-term overall survival. However, there are sparse data on the risk of recurrence based on depth of pathologic response (pT0, pTa, pTis, pT1), and the differential impact of clinicopathologic factors and NAC regimen on recurrence. Methods: Baseline data on all pts with cT2-4N0-1 MIBC receiving NAC and who achieved &lt; ypT2N0 disease at radical cystectomy (RC) from 9 international centers were obtained. The key outcome was time to recurrence (TTR) – defined as the time to any recurrence in the urinary tract or regional/distant metastasis, with death (in the absence of recurrence) considered a competing risk. Cox regression analysis was used to analyze the impact of clinical factors on recurrence. Results: A total of 506 pts were available. Median age was 66 years (range 33-86) and 78% (n = 396) were male; median follow-up after RC was 2.6 years. The majority of patients had pure urothelial histology (n = 371, 73%), and baseline stage was cT2N0 (n = 368, 73%), cT3-4N0 (n = 95, 19%) and TanyN1 (n = 43, 9%). NAC regimens were gemcitabine-cisplatin (GC, n = 296, 59%), dose-dense methotrexate-vinblastine-doxorubicin-cisplatin (ddMVAC, n = 141, 28%), split-dose GC (n = 29, 6%), MVAC (n = 29, 6%) and non-cisplatin based regimens (n = 11, 2%). At RC, 304 patients (60%) had ypT0N0 disease, 32 (6%) had ypTaN0, 107 (21%) had ypTisN0 and 63 (13%) had ypT1N0. Overall, 43 patients (8%) recurred with a median TTR of 56 weeks (range 7-251); 5-year freedom from recurrence was 87% (95% CI 83-91). The majority (n = 38) recurred outside the urinary tract. On multivariable analysis, ypTa (HR = 3.36 [1.24-9.11]) and ypT1 (HR = 2.88 [1.33-6.22], p = 0.013) disease at RC were predictors of shorter TTR, while female sex was associated with longer TTR (HR = 0.52 [0.27-0.98], p = 0.043). The type of NAC was not predictive of TTR (GC vs. other, HR = 1.49 [0.75-2.97], p = 0.26). Conclusions: To our knowledge, this is the largest study to quantify the risk of recurrence in pts achieving pathologic response after NAC and RC for MIBC. 8% of patients undergoing NAC and achieving &lt; ypT2N0 at RC recurred. Residual ypTa and ypT1 disease conferred a significantly higher risk of recurrence, while ypTis did not; female sex was associated with a lower risk of recurrence. Importantly, the type of cisplatin-based NAC regimen used was not an independent predictor of recurrence.

Immunological predictive and prognostic factors in patients with stage II-III triple negative breast cancer.

e12581 Background: Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Pathologic complete response (pCR) achievement during neoadjuvant chemotherapy (NACT) is very important for these pts as it correlates with long-term outcome. Predictive and prognostic factors for this group of pts are needed. Methods: Since 2014 we treated 98 pts with histologically confirmed stage II-III TNBC with following regimen of NACT: 6 cycles of Cisplatin 75mg/m2 day 1 and Paclitaxel 80mg/m2 days 1, 8, 15, every 4 weeks according to local protocol. After NACT pts proceeded to radical breast surgery with assessing of pathological response. Before the treatment we assessed TILs in biopsy samples of all patients. We also conducted subpopulation analysis of lymphocytes in peripheral blood before treatment. We analyzed CD8+, CD25+, NK and NKT cells as they were reported to be significant earlier. We compared results with median value in reference group (mRG) of healthy women. Results: Among all 98 pts 86 (87%) were operated, pCR was achieved in 60,5% of operated pts. pCR strongly correlated with TILs level: 38,5% for pts with TILs &lt; 5% and 69,8% for pts with TILs &gt; 5% (p = 0,05). We also found that NKT population was associated with pCR: 77,8% vs 45,8% among patients with NKT above mRG and up to mRG, respectively (p = 0,01). It correlated also with tpCR: 22,2% vs 70,6% (p = 0,01). When both CD25+ and NKT population were above mRG pCR rate achieved in 85,7% pts vs 50,0% pts if it was up to mRG (p = 0,049). NK, CD8+ and CD25+ did not show any correlation with pCR. Survival results are presented in table below. NK, NKT and TILs did not show any correlation with survival. Interestingly, CD8+ were also associated with lower incidence of visceral metastases: 42,1% in pts with normal CD8+ and 15,7% in pts with CD8+ above normal (p = 0,19). Conclusions: Not only TILs, but also NKT and CD25+/NKT population in the peripheral blood could be possible predictive factors for patients with stage II-III TNBC receiving NACT. CD8+, CD25+ and NKT populations could be further studied as prognostic markers for this group of patients. [Table: see text]

Myosteatosis to predict postoperative morbidity in pancreatic ductal adenocarcinoma patients receiving neoadjuvant chemotherapy.

e16754 Background: Myosteatosis (adipose deposits in muscle) can be detected on cross-sectional imaging through variations in Skeletal Muscle Density (SMD). Patients with myosteatosis tend to have lower overall survival, increased chemotherapy toxicity, and shorter progression-free intervals across cancer types. We investigated whether changes in myosteatosis during neoadjuvant chemotherapy can predict postoperative morbidity risk in patients with pancreatic ductal adenocarcinoma (PDAC). Methods: This is a retrospective cohort study from 2014-2019 of patients with biopsy-proven PDAC who completed neoadjuvant chemotherapy and R0/1 resection (R1: margin &lt; 1mm or microscopically positive). We obtained preoperative patient (age at diagnosis, baseline body mass index (BMI), sex, race, comorbidities) and treatment data (neoadjuvant chemotherapy regimen and duration, time from completion of systemic therapy to surgery, type of operation). Primary outcomes were postoperative complications and 90-day readmission. Average SMD was measured using imaging analysis software at the L3 level on axial abdominal CT scans at the time of diagnosis and at completion of neoadjuvant therapy (SliceOmatic TomoVision QC, Can). We defined SMDΔ as the decrease in SMD during neoadjuvant chemotherapy. Descriptive statistics and Student’s t-test were performed with STATA. Results: We identified 44 patients who received neoadjuvant chemotherapy, achieved a R0/1 resection, and had available CT scans for body composition evaluation. The postoperative complication rate was 43% (n = 19) and 90-day readmission rate was 30% (n = 13). Lower SMD at diagnosis was associated with increased postoperative delirium (p &lt; 0.01) and 90-day readmission (p = 0.02). Greater SMDΔ was associated with increased ICU utilization (p &lt; 0.01) and tube feeding upon discharge (p = 0.03). There was no significant association between preoperative BMI or albumin and our primary outcomes. Conclusions: Preoperative SMD and SMDΔ, rather than albumin or BMI, can predict postoperative morbidity in PDAC patients who received neoadjuvant chemotherapy. This study provides the framework for future studies to develop and validate a tool to predict postoperative morbidity risk in these patients.

A single institution study on the demographics and response rates of Hispanic women with HER2+ disease.

e19069 Background: Hispanics have 20% lower incidence of breast cancer than the general US population. Despite this, breast cancer is the leading neoplasm seen in Hispanics and is a significant cause of their mortality. Our study reports the incidence and outcome of HER2 breast cancer, use of a neoadjuvant regimen, and surgery type in the Hispanic population at our urban institution. Methods: This study reports on 37 women that were diagnosed with HER2+, non-metastatic breast cancer from 2015-2019. We report this as a single institution, community program that provides equal access healthcare and delivery. Our data was investigated and compiled using our facility’s cancer registry. The patient sample included 20(54%) Hispanics, 13(35%) African Americans, 3(8.0%) Caucasians and 1(3%) Asian. Of the 20 Hispanic women, 85% were Estrogen Receptor (ER) positive and 48% were Progesterone Receptor (PR) positive. Eleven (55%) of the 20 Hispanic patients(pts) received neoadjuvant chemotherapy (NAC), which included regimens containing Trastuzamab (H) with or without Pertuzumab(P). Our remaining 9 pts receiving adjuvant therapy were investigated for response as well. Results: Our Hispanic pts receiving NAC had an overall complete response rate of 45% and a partial response rate of 55%. There appeared to be no significant difference in response rate in Hispanic women between the HP group versus H. NAC pts had fewer partial mastectomies performed than those not receiving NAC. Hispanic NAC patients were found to have significantly more sentinel lymph node dissections (SLND) 7(88%) versus axillary lymph node dissections 1(16%) compared to other ethnicities receiving NAC. Non NAC Hispanic patients had 56% sentinel lymph node dissections, compared to 44% complete axillary dissections. Conclusions: The results indicate that there is a significant Hispanic population at our facility that harbor the HER2 oncogene. These pts seem to have a promising response to the NAC regimen in regards to SLND. We hope to have a larger patient sample through a multi-institution study, with statistical analysis to support our current findings. More studies should be performed on Hispanic women with HER2 disease, as data with this subset of population is lacking. The NAC regimen should be greatly considered and implemented in the treatment in those looking to downstage axillary disease. We hope to further investigate treatment options for Hispanic pts to gain greater pathological responses, leading to improved progression free and disease free survival that match that of other ethnic groups.

Neoadjuvant chemotherapy regimens for triple-negative breast cancer: Insights from network meta-analysis.

e12635 Background: The best regimen for neoadjuvant chemotherapy for triple-negative breast cancer (TNBC) is unknown. Recent studies have shown promising data that adding carboplatin improves the rate of pathological complete response (pCR) in TNBC). Therefore, we performed a network meta-analysis to define the overall most effective neoadjuvant systemic therapy for TNBC. Methods: We searched MEDLINE, Cochrane Library, and EMBASE from inception to December 2019 for studies comparing the efficacy of different neoadjuvant regimens in patients with TNBC. We performed a network meta-analysis comparing the regimens in the selected studies using the random-effects model. We focused on anthracycline (A), bevacizumab (B), everolimus (E), and platinum salts (Pl) because these are the medications commonly added to taxane based regimens. All studies contained a taxane regimen. We analyzed the rate of pCR (ypT0/is, N0) and the incidence of grade 3-4 neutropenia, thrombocytopenia, nausea/vomiting, and diarrhea. Results: We identified a total of 13 randomized control trials for this analysis. We compared eight different classes of regimens. We found that regimens containing Pl were significantly superior to Pl non-containing regimens for the rate of pCR. (risk ratio (RR) for pCR [95% confidence interval (CI)]: 1.66 [1.19-2.31], 1.37 [1.14-1.64], and 1.36 [1.14-1.62] for no medications of special interest vs Pl, A vs A+Pl, and A+B vs A+B+Pl, respectively). Regimens containing B were associated with a significantly better rate of pCR. (RR for pCR [95% CI]: 1.24 [1.06-1.46] and 1.23 [1.01-1.51] for A vs A+B and A+Pl vs A+B+Pl, respectively) In contrast, adding A into the regimen did not improve the rate of pCR. In the safety analysis, regimens containing Pl were associated with a significantly higher incidence of grade 3-4 neutropenia and thrombocytopenia. Regimens containing B showed a higher incidence of grade 3-4 nausea/vomiting, and diarrhea. Conclusions: For TNBC, adding Pl or B into the neoadjuvant therapy regimen brings about a higher pCR rate, though they are associated with an increase in hematologic or gastrointestinal complications. The benefit of adding A to the neoadjuvant chemotherapy regimen for TNBC is not apparent.

Neoadjuvant docetaxel + carboplatin versus epirubicin+cyclophosphamide followed by docetaxel in triple-negative, early-stage breast cancer (NeoCART): Results from a multicenter, randomized controlled, open-label, phase II trial.

586 Background: Taxane- and anthracycline-based neoadjuvant regimens have become a standard treatment for triple-negative breast cancer (TNBC). Previous studies have shown that adding carboplatin to neoadjuvant chemotherapy regimens significantly improved pCR rate in TNBC patients. The NeoCART study was designed to compare the efficacy and safety of docetaxel plus carboplatin with standard neoadjuvant chemotherapy in TNBC. Methods: NeoCART was designed as a multicenter, randomized controlled, open-label, phase 2 trial. The patients enrolled were at least 18 years old with previously untreated stage II-III (T1cN1-2 or T2-4N0-2) invasive TNBC who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. All eligible patients were randomly assigned, in a 1:1 ratio, to the experimental arm (docetaxel (75 mg/m2) plus carboplatin (AUC 6) for six cycles) or the standard treatment arm (epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 four cycles, followed by docetaxel 100 mg/m2 for four cycles). The primary end point was the pCR rate (ypT0/is and ypN0). Secondary endpoints included event-free survival, frequency of breast-conserving surgery, and safety. Results: Between September 1, 2016, and December 31, 2019, 88 patients from 6 participating centers were included and randomized (44 patients to the DCb arm and 44 to the EC-D arm). In the primary end point analysis, 27 patients (61.4%, 95% CI 47.0 - 75.8) in the DCb group achieved a pCR compared with 17 patients (38·6%, 95% CI 24.3 - 53.0) in the EC-D group (odds ratio 2.52, 95% CI 2.4 - 43.1; p = 0.033). In different stage disease, the pCR rates of the DCb and the EC-D groups were 73.3% (22/30) vs 48.4% (15/31) in stage II (p = 0.046), and 35.7% (5/14) vs 15.4% (2/13) in stage III (p = 0.384). In patients with axillary lymph node involvement, the pCR rates were 45.8% (11/24) vs 30.8% (8/26) (p = 0.273); and 80.0% (16/20) vs 50.0% (9/18) with lymph node negative disease (p = 0.052). The frequency of breast-conserving surgery in the DCb and EC-D groups was 36.4% and 37.2%, respectively (p = 0·935). The grade 3/4 adverse events include anemia (4.5%), thrombocytopenia (2.3%), neutropenia (2.3%) and ALT/AST increased (2.3%) in the DCb group. Conclusions: Compared with the standard neoadjuvant regimen, docetaxel combined with carboplatin showed a higher pCR rate in TNBC. The higher pCR rate was more significant in patients with earlier disease stage and negative lymph node. Clinical trial information: NCT03154749 .

Efficacy of carboplatin-based chemotherapy regimens in patients with bladder cancer in the neoadjuvant setting.

e17001 Background: There is paucity of evidence regarding efficacy of neoadjuvant chemotherapy regimens in bladder cancer patients. Radical cystectomy has been standard of care for patients with T2-T4, N0, M0 bladder cancer. However, recent trials have shown better survival rates in patients who underwent neo-adjuvant chemotherapy. Our meta-analysis is based on the data from non-randomized clinical trials on the efficacy of carboplatin based regimens. Methods: We conducted a systematic search of Medline (Pubmed) and Cochrane (from inception through May, 2018). Only published single arm clinical trials, abstracts of single arm clinical trials and data from one randomized trial on efficacy of neoadjuvant Carboplatin based therapies in patients with bladder cancer were included in our meta-analysis. Total of &gt; 70 studies were identified. Studies which were duplicate, included adjuvant therapy, systematic reviews or meta-analysis, trials not based on neoadjuvant therapy were excluded. A random effect model was used to calculate pooled proportions. Studies based on ITT protocol were analyzed separately as well as studies based on per protocol analysis. Comprehensive Meta-Analysis software version 3.0 was used. Results: The pooled proportion of pCR (pathologic complete response) calculated from trials based on ITT analysis was 0.23 (95% CI 0.19 to 0.28, P= 0.000). Tests for statistical heterogeneity was non-significant heterogeneity p-value = 0.79 (I2 = 0 %). The pooled proportion of pCR calculated from trials based on per-protocol analysis was 0.29 (95% CI 0.19 to 0.42, P= 0.002). Tests for statistical heterogeneity show nonsignificant heterogeneity p-value = 0.95 (I2 = 0 %). The pooled proportion of ORR (objective response rate) calculated from trials based on per-protocol analysis was 0.69 (95% CI 0.57 to 0.78, P= 0.001). Tests for statistical heterogeneity showed heterogeneity p-value = 0.203 (I2 = 37.3). The pooled proportion of cCR (clinical Complete response) calculated from trials based on per-protocol analysis was 0.25 (95% CI 0.18 to 0.34, P= 0.000). Tests for statistical heterogeneity did not show heterogeneity p-value = 0.80 (I2 = 0%). The pooled proportion of cPR (clinical Partial Response) calculated from trials based on per-protocol analysis was 0.47 (95% CI 0.39 to 0.56, P= 0.59). Tests for statistical heterogeneity did not show heterogeneity p-value = 0.93 (I2 = 0%). Conclusions: Carboplatin based chemotherapy has shown significant efficacy in terms of over-all response rate, pathologic complete response and clinical complete response.

Characterization of weakly hormone receptor (HR)-positive, HER- negative breast cancer (BC) and current treatment strategies.

e12621 Background: HR and HER2 status is critical for determining initial management of BC. Current guidelines define estrogen receptor (ER) and progesterone receptor (PR)+ as ≥1%. Previous reports of small cohorts with low HR+/HER2- disease showed similar rates of pathologic complete response (pCR) following neoadjuvant chemotherapy (NAC) as triple negative BC (TNBC). This study aims to further characterize this group of patients (pts), focusing on modern management and breast/axillary pCR rates following NAC. Methods: Pts with newly diagnosed stage I-III, HR+/HER2- BC from 1/1/2009–4/1/2019 were found using the University of Wisconsin Hospital and Clinics Cancer Registry. Medical records were reviewed for demographics, tumor characteristics with quantification level of ER and PR ( &lt; 33%), treatments including NAC and adjuvant chemotherapy (chemo), endocrine therapy, surgery and radiation, and follow-up clinical data. Results: Data reviewed from 2,905 pts: 2,604 (89.6%) were HR+/HER2-, 282 (9.7%) were ER+/PR-, and 19 (0.7%) were ER-/ PR+. A total of 64 pts [median age 54 (22-87), 100% female] met inclusion criteria. At diagnosis, 23 (36%) were anatomic stage 1, 30 (47%) stage II, and 11 (17%) stage III; 18 (28%) had biopsy (bx) proven nodal disease. 57 (89%) had invasive ductal carcinoma; 9 (14%) were ER+/PR+, 43 (67%) ER+/PR-, and 12 (19%) ER-/ PR+. The majority [51 (80%)] received chemo, ~ half with NAC 30 (48%), 1 pt chemo plan was unknown. NAC regimens included an anthracycline (A) and taxane (T) [26 (41%)], a sole A regimen [1 (1%)], and an A+T and platinum regimen [3 (5%)]. 4 pts received capecitabine after NAC. 50 (78%) pts had a sentinel lymph node bx, but 13 (20%) had an axillary node dissection (ALND). 10 (16%) pts did not receive any endocrine therapy, 28 (44%) got tamoxifen, 22 (34%) an aromatase inhibitor, and 4 (6%) unknown. Of 28 pts who had NAC followed by breast and axillary surgery, 12 (43%) had pCR (ypT0/Tis/ypN0). Of the 12 pts who had bx proven nodal disease at diagnosis and NAC, 7 (64%) pts had pCR at the axilla. One pt had progressive disease on NAC, 1 had local recurrence and 8 (13%) pts had distant recurrence. Median time to recurrence was 13.6 (5.6 – 48.7) months. Only 2 pts with pCR had distant recurrence. Conclusions: BC that are HER2- and weakly HR+ treated with NAC demonstrated an axillary and overall pCR rate more similar to TNBC than breast cancers with strong HR+. Neoadjuvant approaches may reduce need for ALND and pCR may provide important prognostic information. Clinical trials should be developed to focus on this unique patient cohort.

Value of CXCL8-CXCR1/2 axis in neoadjuvant chemotherapy for triple-negative breast cancer patients: a retrospective pilot study.

In this study we investigate the prediction and prognostic value of CXCL8-CXCR1/2 axis for Triple-negative breast cancer (TNBC) patients underwent neoadjuvant chemotherapy (NAC) following standard radical surgery. A total of 303 TNBC patients were included in this study. The NAC regimen was weekly paclitaxel plus carboplatin (PC) for all patients. Serum CXCL8 level was measured at baseline and at surgery via Enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry was used to detect CXCR1 and CXCR2 expression in patients with residual tumors after NAC. Correlations between variables and treatment response were studied, and Cox proportional hazards regression analysis was implemented for prognostic evaluation. Of the 303 patients, 103 (34.0%) patients experienced pathological complete response (pCR) after completion of NAC. CXCL8 level was significantly upgraded after NAC in CXCR1/2+ patients and downgraded after NAC in CXCR1/2- patients. Higher pCR rate was more likely observed in patients with lower CXCL8 level at surgery (P = 0.004, HR 0.939, 95% CI 0.900-0.980). In the multivariate survival model, CXCR1/2 expression was of an independent prognostic value for survival (CXCR1/2+, HR 2.149, 95% CI 0.933-4.949; CXCR1/2++, HR 3.466, 95% CI 1.569-7.655, CXCR1/2- was used as a reference; P = 0.003). Patients with higher level of CXCR1/2 expression were more likely to suffer unfavorable outcome. This study contributes to the clarification of the value of serum CXCL8 level to predict pCR for TNBC patients, and prognostic performance of CXCR1/2 in non-pCR responders after NAC. The CXCL8-CXCR1/2 might play an important role in tailoring and modifying the NAC strategy for advanced TNBCs; however, further confirmatory studies are needed.