Neoadjuvant Chemotherapy Regimen Research Articles

Usefulness of neoadjuvant chemotherapy in non-metastatic muscle-invasive bladder cancer

ObjectiveWe analyzed the profile of patients who were candidates for neoadjuvant chemotherapy (NACT) in stage pT2-4aN0M0, the tolerability and adherence of our cisplatin-based protocol and oncological outcomes. Material and methodsRetrospective observational cohort study including patients diagnosed with muscle-invasive bladder carcinoma treated with NACT. Clinical, histopathological, therapeutic and evolutionary characteristics of the patients were analyzed. The use of NACT was evaluated by the complete response in the surgical specimen (pT0). This and other pathological factors were related to overall survival and progression-free survival. ResultsWe included 90 patients with muscle-invasive bladder carcinoma (clinical stage T2a-T4aN0M0) who received a cisplatin-based NACT regimen between January 2011 and December 2018, prior to radical surgery. Forty percent of patients presented an adverse reaction, with a compliance with the NACT regimen of 92.2%. There were no deaths related to systemic treatment and no adverse reaction to treatment made RC impracticable. After performing RC, the presence of complete response (pT0) was observed in 20 patients (21%), lower stage in the surgical specimen (<pT2) in 36 patients (40%), positive surgical margins in 7 patients (8%), lymph node involvement (N1) in 16 patients (17.8%). A shorter time to progression was observed in the group of patients who did not achieve a complete pathological response (53 months vs 83.1 in pT0 patients) (p = 0.012), in patients with lymph node involvement compared to pN0 (65.4 vs 28, 2 months) (p = 0.014) and in those with positive surgical margins compared to those with tumor-free margins (63.5 vs. 8.5 months) (p = 0.021). ConclusionThe adequate selection of patients with MIBC has shown a good tolerance to NACT, with a high compliance rate prior to RC. The improvement in the complete response rate implies a greater survival in this group of patients, with lymph node involvement and positive surgical margins being important prognostic factors.

Factors Associated with Nodal Pathologic Complete Response Among Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: Results of CALGB 40601 (HER2+) and 40603 (Triple-Negative) (Alliance).

De-escalation of axillary surgery after neoadjuvant chemotherapy (NAC) requires careful patient selection. We seek to determine predictors of nodal pathologic complete response (ypN0) among patients treated on CALGB 40601 or 40603, which tested NAC regimens in HER2+ and triple-negative breast cancer (TNBC), respectively. A total of 760 patients with stage II-III HER2+ or TNBC were analyzed. Those who had axillary surgery before NAC (N = 122), or who had missing pretreatment clinical nodal status (cN) (N = 58) or ypN status (N = 41) were excluded. The proportion of patients with ypN0 disease was estimated for those with and without breast pathologic complete response (pCR) according to pretreatment nodal status. In 539 patients, the overall ypN0 rate was 76.3% (411/539) to 93.2% (245/263) in patients with breast pCR and 60.1% (166/276) with residual breast disease (RD) (P < 0.0001). For patients who were cN0 pretreatment, the ypN0 rate was 88.8% (214/241), 96.3% (104/108) with breast pCR, and 82.7% (110/133) with RD. For patients who were cN1, 66.2% (157/237) converted to ypN0, 91.7% (111/121) with breast pCR and 39.7% (46/116) with RD. For patients who were cN2/3, 65.6% (40/61) converted to ypN0, 88.2% (30/34) with breast pCR and 37.0% (10/27) with RD. On multivariable analysis, only pretreatment clinical nodal status and breast pCR/RD were associated with ypN0 status (both P < 0.0001). Breast pCR and pretreatment nodal status are predictive of ypN0 axillary nodal involvement, with < 5% residual nodal disease among cN0 patients who experience breast pCR. These findings support the incorporation of axillary surgery de-escalation strategies into NAC trials.

Down-regulation of immune checkpoints by doxorubicin and carboplatin-containing neoadjuvant regimens in a murine breast cancer model.

Objective(s): Immune checkpoint expression on tumor-infiltrating lymphocytes (TILs) has a correlation with the outcome of neoadjuvant chemotherapy (NAC) in breast cancer. However, the reciprocal effect of these regimens on the quality and quantity of immune checkpoints has hitherto not been addressed. We aimed to evaluate the impact of three NAC regimens on TILs and immune checkpoints in a murine triple-negative breast cancer model.Materials and Methods:Syngeneic model of locally-advanced breast cancer was established in immunocompetent mice using a 4T1 cell line. Tumor-bearing animals were treated with human-equivalent dosages of doxorubicin, paclitaxel, paclitaxel and carboplatin combination, and placebo. Infiltration of CD3+, CD8+, and FoxP3+ cells into the tumor was assessed by immunohistochemistry. Expression of immune checkpoints, including PD-1, CTLA-4, and TIM-3, was evaluated by real-time PCR.Results:Doxorubicin led to a significant (P<0.01) increase in the percentage of the stromal infiltrating CD3+ and CD8+ lymphocytes. Doxorubicin also suppressed significantly (P<0.05) the relative expression of PD-1 compared with the placebo. PD-1 expression was significantly (P<0.05) lower in the group treated with paclitaxel and carboplatin combination as compared with the placebo. The relative expression of TIM-3 was significantly (P<0.05) suppressed in doxorubicin-treated mice in comparison with other interventions.Conclusion:Our findings hypothesize that NAC with doxorubicin may potentiate antitumor immunity not merely by recruitment of TILs, but via down-regulation of PD-1 and TIM-3 checkpoints. Carboplatin-containing NAC may suppress PD-1 as well.

Efficacy and safety of vinorelbine and cisplatin regimen of different doses and intensities for neoadjuvant chemotherapy in patients with locally advanced esophageal carcinoma.

BackgroundThere are few studies focused on comparing the toxicity, postoperative complication rate, and survival among patients with locally advanced esophageal squamous cell cancer receiving a different dose and intensity of vinorelbine plus cisplatin for neoadjuvant chemoradiotherapy (nCRT) followed by surgery.MethodsIn total, 78 patients diagnosed with locally advanced esophageal squamous cell cancer that had received a vinorelbine and cisplatin (VP)1 or VP2 regimen for nCRT followed by surgery in Taizhou Hospital of Zhejiang Province between June 2008 and December 2016 were retrospectively analyzed. The VP1 regimen involved cisplatin 75 mg/m2 on day 1, and vinorelbine 25 mg/m2 on days 1 and 8, for two cycles. The VP2 regimen involved cisplatin 25 mg/m2 on days 1 to 4, and vinorelbine 25 mg/m2 on days 1 and 8, for two cycles. The rate of adverse events, postoperative complications, and survival were compared between the two groups.ResultsThe median overall survival (OS) was 97.6 months (85.6–109.7) in the VP2 group, which was not significantly different to that of the VP1 group [hazard ratio (HR), 1.008 (0.999–1.108); P=0.509]. The main toxicity was hematologic adverse events. The VP2 group had significantly higher rates of all grades of anemia, leukopenia, neutropenia, and thrombocytopenia (all P<0.05), as well as grade 3 or 4 of leukopenia and neutropenia (P<0.05) compared to the VP1 group. Regarding postoperative complications, the VP2 group had a significantly higher rate of pulmonary infection than the VP1 group (P<0.05).ConclusionsCompared with VP2, VP1 showed comparable efficacy in terms of survival, with less hematologic toxicity and postoperative pulmonary infection. Therefore, we recommended that VP1 over VP2 to be the optimized VP neoadjuvant chemotherapy regimen for locally advanced esophageal squamous cell cancer.

Effects of MDR1 Gene Polymorphism on Efficacy and Hematotoxicity of Epirubicin-Based Regimen in Patients with Breast Cancer in Southwest China

Objective: To investigate the predictive value of multi-drug resistance gene (MDR1) polymorphism in the efficacy and hematological toxicity of chemotherapy regimen based on Epirubicin in patients with breast cancer in Southwest China. Methods: Patients who received Epirubicin-based chemotherapy were included, and polymorphism of C1236T, G2677T/A and C3435T were detected by time-of-flight mass spectrometry (TOF-MS). The correlation between different genotypes and chemotherapy efficacy and blood toxicity were evaluated. Results: A total of 102 patients were included, 44 of them were treated with neoadjuvant chemotherapy. There was no significant correlation between all genotypes and alleles of the three SNPs and the efficacy of neoadjuvant chemotherapy regimen containing Epirubicin in patients with breast cancer. There was a significant correlation between C3435T polymorphism and grade Ⅲ-Ⅳ leukopenia in patients with breast cancer, the incidence of grade Ⅲ-Ⅳ leukopenia in patients with C allele was significantly lower than that in patients with T allele. Conclusion: T allele of C3435T polymorphism may be a risk factor for grade Ⅲ-Ⅳ leukopenia in patients with breast cancer after chemotherapy.

Neoadjuvant Chemotherapy of Triple-Negative Breast Cancer: Evaluation of Early Clinical Response, Pathological Complete Response Rates, and Addition of Platinum Salts Benefit Based on Real-World Evidence.

Simple SummaryNeoadjuvant chemotherapy (NACT) is the standard treatment for early-stage triple-negative breast cancer (TNBC). Achieving pathological complete response (pCR) is considered an essential prognostic factor with favorable long-term outcomes. The administration of NACT regimens with platinum salts is associated with a higher pCR rate. However, with unclear treatment guidelines and at the expense of a higher incidence of adverse events. Identifying patients and circumstances in which the benefits of platinum NACT outweigh inconveniences is still an ongoing challenge. Considering early clinical response (ECR) after the initial standard NACT cycles together with other suitable predictors could be useful to decide about the administration of platinum salts in clinical practice. The results of this large single institutional retrospective study of consecutive patients showed the significant role of adding platinum salts in older patients with high-proliferative early responded tumors and persisted lymph nodes involvement regardless of BRCA1/2 status.Pathological complete response (pCR) achievement is undoubtedly the essential goal of neoadjuvant therapy for breast cancer, directly affecting survival endpoints. This retrospective study of 237 triple-negative breast cancer (TNBC) patients with a median follow-up of 36 months evaluated the role of adding platinum salts into standard neoadjuvant chemotherapy (NACT). After the initial four standard NACT cycles, early clinical response (ECR) was assessed and used to identify tumors and patients generally sensitive to NACT. BRCA1/2 mutation, smaller unifocal tumors, and Ki-67 ≥ 65% were independent predictors of ECR. The total pCR rate was 41%, the achievement of pCR was strongly associated with ECR (OR = 15.1, p < 0.001). According to multivariable analysis, the significant benefit of platinum NACT was observed in early responders ≥45 years, Ki-67 ≥ 65% and persisted lymph node involvement regardless of BRCA1/2 status. Early responders with pCR had a longer time to death (HR = 0.28, p < 0.001) and relapse (HR = 0.26, p < 0.001). The pCR was achieved in only 7% of non-responders. However, platinum salts favored non-responders’ survival outcomes without statistical significance. Toxicity was significantly often observed in patients with platinum NACT (p = 0.003) but not for grade 3/4 (p = 0.155). These results based on real-world evidence point to the usability of ECR in NACT management, especially focusing on the benefit of platinum salts.

Role of Platinums in Triple-Negative Breast Cancer.

Platinum compounds are used in the treatment of various types of cancer. Here, we review the current role of cisplatin and carboplatin in the treatment of early stage and advanced triple-negative breast cancer (TNBC), and the use of biomarkers in predicting response to platinum therapy. Addition of carboplatin to a neoadjuvant chemotherapy regimen can result in improvement in the pathological complete response rates. The long-term benefit of the addition of carboplatin to standard chemotherapy regimens remains unproven. Single-agent platinum is an option in the treatment of advanced breast cancer. BRCA1/2 mutations predicted benefit from platinums in advanced, but not early stage breast cancer. There are yet no biomarkers to predict response to platinum in sporadic TNBC. Platinum compounds are an option in the treatment of TNBC. Identification of biomarkers to select tumors most likely to derive benefit from these agents is still needed. Ongoing trials are exploring the role of platinum in the adjuvant setting and in combination with other agents, including immune checkpoint inhibitors.

Comparison of clinical outcomes in patients with localized or locally advanced urothelial carcinoma treated with neoadjuvant chemotherapy involving gemcitabine-cisplatin and high dose-intensity MVAC.

To compare the efficacy and safety of high dose-intensity combination of methotrexate, vinblastine, adriamycin and cisplatin (HD MVAC) with gemcitabine plus cisplatin (GC) as a neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC) or locally advanced upper tract urothelial cancer (UTUC). A retrospective analysis was conducted for patients with UC (cT2-4aN0-1M0) who received NAC from January 2011 and December 2017 at Asan Medical Center. Pathologic complete response (pCR), down-staging (< ypT2 and no N upstaging), disease-free survival (DFS), OS and safety were compared for each regimen. Out of a total of 277 patients, 176 patients received GC and 41 patients received HD MVAC. With the exception of age (patients receiving HD MVAC were younger; p = 0.002), other baseline characteristics were well balanced between groups. pCR rates were 27.0% for GC and 22.6% for HD MVAC (p = 0.62), and down-staging rate was 50.8% for GC and 58.1% for HD MVAC (p = 0.47). There were no differences in OS (72.1% vs 73.1% for GC vs HD MVAC; p = 0.58) and DFS (54.9% vs 63.3% for GC vs HD MVAC; p = 0.21) at 3years. HD MVAC with prophylactic G-CSF was associated with a higher incidence of febrile neutropenia (p < 0.001) than GC. The NAC regimen was not an independent prognostic factor for OS. Oncologic outcomes were not significantly different between the GC and HD MVAC when used as NAC in MIBC/UTUC.

Clinical Perspective on Proteomic and Glycomic Biomarkers for Diagnosis, Prognosis, and Prediction of Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is known as a highly aggressive malignant disease. Prognosis for patients is notoriously poor, despite improvements in surgical techniques and new (neo)adjuvant chemotherapy regimens. Early detection of PDAC may increase the overall survival. It is furthermore foreseen that precision medicine will provide improved prognostic stratification and prediction of therapeutic response. In this review, omics-based discovery efforts are presented that aim for novel diagnostic and prognostic biomarkers of PDAC. For this purpose, we systematically evaluated the literature published between 1999 and 2020 with a focus on protein- and protein-glycosylation biomarkers in pancreatic cancer patients. Besides genomic and transcriptomic approaches, mass spectrometry (MS)-based proteomics and glycomics of blood- and tissue-derived samples from PDAC patients have yielded new candidates with biomarker potential. However, for reasons discussed in this review, the validation and clinical translation of these candidate markers has not been successful. Consequently, there has been a change of mindset from initial efforts to identify new unimarkers into the current hypothesis that a combination of biomarkers better suits a diagnostic or prognostic panel. With continuing development of current research methods and available techniques combined with careful study designs, new biomarkers could contribute to improved detection, prognosis, and prediction of pancreatic cancer.

Stage III colon cancer: is neoadjuvant chemotherapy ready for prime time?—A narrative review of neoadjuvant chemotherapy for colon cancer

: The current standard of care for stage III colon cancer has been adjuvant chemotherapy since this was first shown to be beneficial three decades ago. Despite the improvement in outcomes after introduction of oxaliplatin a decade ago, relapse rates are still significant with associated high morbidity and mortality related to metastatic colon cancer worldwide. Discovery of novel agents for use in colon cancer has been slow and disappointing. Repurposing currently available drugs with known activity in colon cancer into a neoadjuvant chemotherapy regimen has the potential to improve outcomes in colon cancer even while we await development of new drugs. Clinical trials of neoadjuvant chemotherapy for colon cancer to date have been encouraging, demonstrating lower pathologic stage amongst treated patients, and higher rates of R0 resection. However, only early data is available and long term survival outcomes are eagerly awaited. Challenges include optimal staging and patient selection for neoadjuvant therapy, with current methods of radiologic staging lacking specificity to exclude low risk patients (who might not require chemotherapy) from trials. Novel approaches, a notable example being the use of immunotherapy for mismatch repair (MMR) deficient tumours, hold promise of higher response rates without increasing toxicity. Neoadjuvant chemotherapy for this disease still requires further data to be available before it is ready for widespread use, however shows great promise. This review article will discuss the available data regarding rationale and evidence for neoadjuvant chemotherapy for colon cancer.

Evaluation of the Effects of Letrozole in Combination with Neoadjuvant Chemotherapy on Clinical Response Rate of Breast Cancer

AbstractThis randomized clinical trial was aimed to assess the efficacy of neoadjuvant letrozole in combination with standard neoadjuvant chemotherapy regimen on clinical response rate of hormone receptor positive locally advanced breast cancer.In this randomized clinical study, 42 female patients, ≥ 18 years, with clinical stage IIB-IIIC (T1-4, N0-3, M0), pathologically proven hormone receptor positive and HER2 negative, invasive ductal carcinoma of breast, were randomly assigned to receive standard neoadjuvant chemotherapy alone (control group) or letrozole 2.5 mg/d (in association with goserlin in premenopausal patients) concurrent with standard neoadjuvant chemotherapy (study group). Standard neoadjuvant chemotherapy regimen has consisted of 4 cycles of doxorubicin (60mg/m2) and cyclophodphamide (600mg/m2), followed by 4 cycles of paclitaxel (175mg/m2) every two weeks.At the beginning of the study all patients underwent thorough exmination of breast mass and axillary lymph nudes by palpation and ultrasonography. At the end of the study response rates were also evaluated by palpation and ultrasonography and subsequently patients were referred for surgury. Pathologic response rates were also evaluated on surgical specimens. All of the clinical, ultrasonographic and pathologic examinations during the trial were performed by a single specialist. Finally all the data were analysed statistically.Overall clinical response rates in breast were 95.2%, in both study and control group. Overall clinical response rates in axilla were 80.9% and 76.2% in study and control group respectively. Similarly, overall radiologic complete response rates in breast and axilla were 95.2% and 76.2% respectively in both study and control group. Totally, the comparison of overall clinical and radiologic response rates in th breast and axilla, showed no significant difference between control and study group (p>0.05).The addition of letrozol to standard neoadjuvant chemotherapy regimen was not associated with higher clinical and radiologic response rates in patients with locally advanced hormon receptor positive breast cancer.Keywords: Neoadjuvant chemotherapy, Letrozole, Locally advanced breast cancer

Safety and effectiveness of oxaliplatin combined with capecitabine or oxaliplatin combined with S-1 neoadjuvant chemotherapy in the treatment of advanced gastric cancer

Objective: To explore the safety and efficacy of oxaliplatin plus capecitabine (CapeOX) or oxaliplatin plus S-1 (SOX) regimen neoadjuvant chemotherapy in the treatment of advanced gastric cancer. Methods: A retrospective cohort study was performed. Clinical data of patients diagnosed as advanced gastric cancer undergoing CapeOX/SOX neoadjuvant chemotherapy and standard laparoscopic radical operation for gastric cancer in Ruijin Hospital of Shanghai Jiaotong University School of Medicine from April 2016 to April 2019 were retrospectively collected. Inclusion criteria were as follows: (1) age≥18 years; (2) gastric adenocarcinoma was confirmed by histopathology and the clinical stage was T3-4aN+M0; (3) tumor could be resectable; (4) preoperative neoadjuvant chemotherapy was CapeOX or SOX regimen without radiotherapy or other regimen chemotherapy; (5) no other concurrent malignant tumor; (6) the Eastern Cooperative Oncology Group (ECOG) score ≤ 1; (7) no bone marrow suppression; (8) normal liver and kidney function. Exclusion criteria were as follows: (1) patients with recurrent gastric cancer; (2) patients receiving emergency surgery due to tumor perforation, bleeding, obstruction, etc.; (3) allergy to oxaliplatin, S-1, capecitabine or any drug excipients; (4) diagnosed with coronary heart disease, cardiomyopathy, or the New York Heart Association class III or IV; (5) pregnant or lactating women. A total of 118 patients were enrolled as the neoadjuvant chemotherapy group, and 379 patients with locally advanced gastric cancer who received surgery combined with postoperative adjuvant chemotherapy over the same period simultaneously were included as the adjuvant chemotherapy group. After propensity score matching was performed including gender, age, ECOG score, tumor site, clinical stage, chemotherapy regimen and other factors by 1:1 ratio, there were 40 cases in each group. The differences between the two groups in general conditions, efficacy of neoadjuvant chemotherapy, intraoperative conditions, postoperative conditions, histopathological results, chemotherapy-related adverse events, and survival status were compared and analyzed. Results: Comparison of baseline demographics between the two groups showed no statistically significant difference (all P>0.05). In the neoadjuvant chemotherapy group, 5.0% (2/40) of patients achieved clinical complete response, 57.5% (23/40) achieved partial response, 32.5% (13/40) remained stable disease, and 5.0% (2/40) had disease progression before surgery. Objective response rate was 62.5% (25/40), and disease control rate was 95.0% (38/40). There were no statistically significant differences between neoadjuvant chemotherapy group and adjuvant chemotherapy group in terms of operation time, intraoperative blood loss, number of lymph node harvested, length of postoperative hospital stay, and postoperative mortality and morbidity (all P>0.05). Postoperative complications were well managed with conservative treatment. No Clavien-Dindo IV or V complications were observed in both groups. Pathological results showed that the proportion of patients with pathological stage T1 in the neoadjuvant chemotherapy group was significantly higher than that in the adjuvant chemotherapy group [27.5% (11/40) vs. 5.0% (2/40)], while the proportion of patients with pathological stage T3 was significantly lower than that in the adjuvant chemotherapy group [20.0% (8/40) vs. 45.0% (18/40)], with statistically significant difference (χ(2)=15.432, P=0.001). In the neoadjuvant chemotherapy group, there were 4 cases of tumor regression grade 0, 8 cases of grade 1, 16 cases of grade 2, and 12 cases of grade 3. The pathological complete response rate was 10% (4/40), the overall pathological response rate was 70.0% (28/40). There was no statistically significant difference in the incidence of chemotherapy-related adverse events between neoadjuvant chemotherapy group and adjuvant chemotherapy group [40% (16/40) vs. 37.5% (15/40), P>0.05). There were no statistically significant differences in OS (43 months vs. 40 months) and 3-year OS rate (66.1% vs. 59.8%) between neoadjuvant chemotherapy group and adjuvant chemotherapy group (P=0.428). The disease-free survival (DFS) and 3-year DFS rates of the neoadjuvant chemotherapy group were significantly superior to those of the adjuvant chemotherapy group (36 months vs. 28 months, 51.4% vs. 35.8%, P=0.048). Conclusion: CapeOX or SOX regimen neoadjuvant chemotherapy is a safe, effective and feasible treatment mode for advanced gastric cancer without increasing surgical risk and can improve the DFS of patients.

Postoperative complications and their influence on the prognosis factors in gastric cancer patients receiving neoadjuvant treatment

Objective: To investigate postoperative complications of patients undergoing neoadjuvant therapy followed by radical gastrectomy, and to analyze their influence on the prognosis. Methods: A retrospective case-control study was used. Case inclusion criteria: (1) gastric adenocarcinoma confirmed by histopathology; (2) preoperative imaging examination showed no distant metastasis or peritoneal dissemination; (3) undergoing radical gastrectomy and D2 lymph node dissection after neoadjuvant therapy; (4) complete clinicopathological and follow-up data. According to the above criteria, clinical data of 490 gastric cancer patients who underwent radical gastrectomy in the Cancer Hospital of Chinese Academy of Medical Sciences, Peking Union Medical College from January 2008 to December 2018 were retrospectively collected, including 358 males and 132 females with mean age of (55.0±10.6) years. Neoadjuvant chemotherapy regimens included SOX (S-1+ oxaliplatin, n=151), XELOX (capecitabine+oxaliplatin, n=155), FLOT (docetaxel+oxaliplatin+fluorouracil, n=66), and DOS (docetaxel+ oxaliplatin+S-1, n=68). Preoperative concurrent chemoradiotherapy was performed in 100 patients. SOX regimen was used for 2-4 cycles as induction chemotherapy plus concurrent chemoradiotherapy (3D IMRT+S-1). Postoperative complications were defined as surgery-related complications, mainly including hemorrhage, anastomotic leakage, obstruction, anastomotic stenosis, pulmonary infection, abdominal infection, etc. Postoperative complications were graded according to Clavien-Dindo classification. Log-rank test and Cox regression model were used for univanriate multivariate prognostic analysis, respectively. Results: A total of 101 complications ocaured after operation in 87 (17.8%) patients, including 29 cases of major complications (Clavien-Dindo III to V), and 58 cases of minor complications (Clavien-Dindo I to II). Multivariate analysis showed that age > 65 years (HR=3.077, 95% CI: 1.827-5.184, P<0.001) and total gastrectomy (HR=1.735, 95% CI: 1.069-2.814, P=0.026) were independent risk factors for postoperative complications in patients with gastric cancer undergoing neoadjuvant therapy and radical gastrectomy (both P<0.05). The follow-up period was 0.7 to 131.8 months (median 21.5 months), and the 5-year overall survival rate was 47.4%. The 5-year overall survival rates of the complication group (87 cases) and the non-complication group (403 cases) were 33.2% and 50.9%, respectively (P=0.001). Multivariate analysis showed that age (HR=1.906, 95% CI: 1.248-2.913, P=0.003), ypTNM II to III stage (II stage: HR=5.853, 95% CI: 1.778-19.260, P=0.004; III stage: HR=10.800, 95% CI: 3.411-34.189, P<0.001), surgery time>3.5 h (HR=1.492, 95% CI: 1.095-2.033, P=0.011), total gastrectomy (HR=1.657, 95% CI: 1.216-2.257, P=0.001) and postoperative complications (HR=1.614, 95% CI: 1.125-2.315, P=0.009) were independent risk factors for prognosis, and postoperative adjuvant therapy (HR=0.578, 95% CI: 0.421-0.794, P=0.001) was an independent protective factor for prognosis. Conclusions: The occurrence of postoperative complications in gastric cancer patients undergoing neoadjuvant therapy is closely related to the age of the patients and the range of surgical resection. It is beneficial to improve the prognosis for these patients by paying more attention to the prevention of postoperative complications and the reinforcement of postoperative adjuvant therapy.

Covered self-expandable metal stents versus plastic stents for preoperative biliary drainage in patient receiving neo-adjuvant chemotherapy for borderline resectable pancreatic cancer: Prospective randomized study.

This single-center comparative randomized superiority study compared biliary stenting using fully covered self-expandable metal stents (FCSEMS) and biliary stenting using plastic stents (PS) in preoperative biliary drainage of patients with borderline resectable pancreatic cancer (BRPC) who are planned to undergo a single regimen of neo-adjuvant chemotherapy (NAC). Twenty-two patients with BRPC who required preoperative biliary drainage before NAC (Gemcitabine plus Nab-paclitaxel) were randomly assigned 1:1 to the FCSEMS or PS group. The primary endpoint was the rate of stent dysfunction until surgery or tumor progression. Secondary endpoints were stent patency, number of re-interventions, adverse events of endoscopic retrograde biliary drainage (EBD), operation time, volume of intraoperative bleeding, postoperative hospitalization, postoperative adverse events and medical costs. Eleven patients in each of the groups reached the primary endpoint. The FCSEMS group showed a significantly lower rate of stent dysfunction (18.2% vs. 72.8%, P=0.015), longer stent patency (P=0.02), and lower number of re-interventions for stent dysfunction (0.27±0.65 vs. 1.27±1.1, P=0.001) than the PS group. The adverse events of EBD, operation time, volume of intraoperative bleeding, postoperative hospitalization, postoperative adverse events and medical costs did not significantly differ between the two groups. In patients with BRPC for preoperative biliary drainage, stent dysfunction occurred less frequently withFCSEMSs than with PSs. In addition, FCSEMS and PSprovided similar preoperative management of BRPC in terms ofthesafety of surgery and medical costs. (UMIN ID000030473).

Abstract PS10-33: Analysis of factors associated with pathological complete response (pCR) in patients with HER2+ breast cancer receiving neoadjuvant chemotherapy

Abstract Background: Pathologic complete response (pCR) following neoadjuvant chemotherapy (NAC) is associated with improved survival outcomes among women with HER2 positive (HER2+) breast cancer. We aimed to analyze the clinical, pathological and molecular factors associated with pCR in our series of HER2+ breast cancer patients. Methods: Between 2009 and 2019, breast cancer patients receiving NAC at our centre were enrolled in a prospective database. For this study we selected women with HER2+ unilateral breast cancer stages II or III who received anthracycline-taxane NAC regimens (with trastuzumab given concurrently with the taxane) and subsequently underwent breast and axillary surgery with curative intent. Medical charts of these 161 women were retrospectively reviewed to determine what clinical, pathological and molecular characteristics were associated with pCR using bivariate and multivariate analysis. Results: Of the 161 HER2+ women median age at diagnosis was 49 years (range 25-78) with 90 (56%) women under age 50. Total of 104 (65%) tumors were stage II, 108 (67%) expressed estrogen and/or progesterone receptors, 139 (86%) had HER2 3+ expression by immunohistochemistry (IHC) and 22 (14%) had HER2 IHC 2+ expression with amplified HER2 on fluorescence in situ hybridization (FISH) test. The NAC regimens were: Doxorubicin-Cyclophosphamide-Paclitaxel for 83 (52%) and Fluorouracil-Epirubicin-Cyclophosphamide-Docetaxel for 78 (48%) women. A total of 73 patients [45%; 44/108 HR+ (41%) and 29/53 HR- (55%)] achieved pCR (p=0.94). pCR rate among HER2 IHC 3+ tumors was 69/139 (50%), while for HER2 IHC 2+ tumors was 4/22 (18%). On bivariate analysis HER2 IHC 3+, absence of estrogen receptors and absence of progesterone receptors were predictive of pCR, while age, menopausal status, histologic subtype, tumor grade and NAC regimen were not. In the multivariate model only HER2 IHC 3+ expression remained a significant predictor of pCR (OR =4.443, 95% CI 1.376 - 14.344). Conclusion: Our analysis suggests that for HER2+ breast cancers treated with NAC with anthracycline-taxane and trastuzumab, HER2 IHC 3+ expression is associated with a higher rate of pCR compared to HER2 IHC 2+ expression with FISH amplification. Further analysis in a larger cohort is warranted. Citation Format: Neda Stjepanovic, Katarzyna Jerzak, Maureen Trudeau, Andrea Eisen, Sonal Gandhi, Ellen Warner, Danilo Giffoni MM Mata, Anthony Lott, Maria Romero, Sharon Lemon-Wong, Althea VanMassop, Xingshan Cao, William Tran, Rossanna Pezo. Analysis of factors associated with pathological complete response (pCR) in patients with HER2+ breast cancer receiving neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-33.

Abstract PS6-53: Higher clinical lymph node stage predicts worse survival in patients with breast cancer who achieve a pathologic complete response after neoadjuvant chemotherapy

Abstract Background: Despite patients with breast cancer who achieve a pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) generally demonstrate improved survival, some of these patients will develop breast cancer recurrence. Identification of factors associated with recurrence in patients with pCR after NAC would be helpful to optimize treatment strategies in breast cancer. In this study, we aim to particularly explore the factors associated with the prognosis of this patient population.Methods: Data of patients from three tertiary hospitals and treated with NAC between 2005 and 2019 were retrospectively collected. A pCR was defined as no invasive tumor in the breast and no tumor in the lymph node (ypT0/is, ypN0). Factors associated with pCR were analyzed using univariable and multivariable logistic regression analyses. Disease-free survival (DFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. The prognostic value of clinicopathological factors regarding DFS and OS were determined by univariable and multivariable Cox regression analyses.Results: A total of 897 patients were used for the analysis, including 287 patients with a pCR and 610 patients without pCR. Clinical TNM stage, histological grade, estrogen receptor (ER) status, progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) status, Ki67, molecular subtype, NAC regimen and NAC cycles were associated with pCR status, with TNM stage and molecular subtype as independent predictors of pCR. Patients with a pCR had a superior DFS (pCR vs non-pCR, hazard ratio [HR] 0.26 (95% confidence interval [CI] 0.15-0.45, P&amp;lt;0.001) and OS (pCR vs non-pCR, hazard ratio [HR] 0.13 (95% confidence interval [CI] 0.05-0.35, P&amp;lt;0.001). In patients with pCR, clinical T stage, N stage and TNM stage were associated with DFS and OS, with higher N stage as an independent predictor of a worse DFS and OS.Conclusions:Clinical N stage of breast cancer is an independent predictor of worse DFS and OS in patients with a pCR after NAC. Possible this could support treatment escalation in this patient population in the future. Citation Format: Li-Yun Xie, Kun Wang, Yan-Xia Shi, Hai-Lu Chen, Jian-Hao Huang, Yang-Hang Fan, Si-Qi Qiu, Zhi-Yong Wu. Higher clinical lymph node stage predicts worse survival in patients with breast cancer who achieve a pathologic complete response after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-53.

Abstract GS4-05: Neoadjuvant chemotherapy (NCT) response in postmenopausal women with clinical stage II or III estrogen receptor positive (ER+) and HER2 negative (HER2-) breast cancer (BC) resistant to endocrine therapy (ET) in the ALTERNATE trial (Alliance A011106)

Abstract Background: Ki67 values &amp;gt;10% 2-4 weeks (wks) after starting neoadjuvant ET (NET) indicates persistent cell proliferation, resistance to ET, and is associated with increased risk of recurrence. The ACOSOG Z1031 trial suggested that these tumors are also relatively chemotherapy (chemo) resistant with a low pathologic complete response (pCR) rate to NCT. The ALTERNATE trial (NCT01953588) is a randomized study of neoadjuvant anastrozole (ANA), fulvestrant (FUL), or ANA + FUL in postmenopausal patients (pt) with newly diagnosed clinical stage II or III ER+ (Allred score 6-8)/HER2- BC. Ki67 &amp;gt;10% at wk 4 or 12 after starting NET triggered triage to NCT of physician choice or weekly paclitaxel. Pts who refused protocol-directed therapy, were not candidates for NCT, or decided to undergo immediate surgery are being followed per protocol. Here we report the rates of pCR and residual cancer burden (RCB) following NCT for pts triaged to NCT due to Ki67 &amp;gt;10% at wk 4 or 12. Results: Of the 1,299 eligible pts randomized to receive ANA, FUL, or ANA + FUL, 286 (22%) had Ki67 &amp;gt;10% at wk 4 or 12. 168 of these 286 pts (58.7%) chose to switch to NCT, 32 went to surgery (11.2%), and 86 discontinued further protocol-directed therapy (30.1%). Among the 168 pts who underwent NCT, the presenting clinical T stages were cT2 (n=113; 67.26%), cT3 (n=47; 27.98%) and cT4 (n=8; 4.76%) and N stages were cN0 (n=82; 48.8%), cN1 (n=75; 44.6%), cN2/3 (n=9; 5.4%) and cNx (n=2; 1.2%). Central ER testing was performed on pre-treatment biopsies and confirmed ER Allred score 6-8 in 155 of 168 (92.2%) pts, with the rest being ER Allred score 4-5 (n=5; 3%), ER- (Allred score 0) (n=2; 1.2%), or not tested (n=6; 3.6%). Most (n=139; 82.7%) were ER+/PR+, while 17.3% (n=29) were ER+/PR-, and tumor grades were G1 (n=10; 6%), G2 (n=99; 58.9%), G3 (n=54; 32.1%), not reported (n=5; 3%). Baseline Ki67 levels prior to NET were &amp;gt;10% in 94% (n=158), ≤10% in 3% (n=5), and not done in 3% (n=5). NCT regimens administered included doxorubicin/cyclophosphamide (AC) followed by paclitaxel (T) (n=60; 35.71%); weekly paclitaxel (n=56; 33.33%), docetaxel/cyclophosphamide (TC) (n=33; 19.65%), other doxorubicin and/or taxane containing regimen (n=17; 10.12%), and cyclophosphamide/methotrexate/fluorouracil (CMF) (n=2; 1.19%). 35 (20.8%) pts did not complete planned course of NCT due to toxicity (n=27) or refusal (n=8). 154 NCT pts underwent surgery (mastectomy in 40.3%, and breast conserving surgery in 59.7%). The path ypT stages were Tis/0 (n=10; 6.5%), T1 (n=62; 40.3%), T2 (n=61; 39.6%), and T3/4 (n=21; 13.6%), and the ypN stages were N0 (n=66; 42.9%), N1 (n=57; 37%), N2/3 (n=30; 19.5%), and Nx (n=1; 0.6%). Among the 168 pts who started on NCT (intent to treat population), there were 8 pCRs (no invasive disease in the breast or lymph nodes) (4.8%; 95% CI: 2.1% to 9.2%). Residual Cancer Burden (RCB) categories include RCB 0 (n=8; 4.8%), RCB 1 (n=15; 8.9%), RCB 2 (n=82; 48.8%), RCB 3 (n=42; 25.0%), and not determined (n=21; 12.5%). Correlations of baseline pt and tumor characteristics with pathology response to NCT will also be presented. Conclusion: In pts with NET-resistant ER+/HER2- BC, salvage NCT is not likely to induce a complete or near complete response. More effective treatments are needed for this high-risk ER+/HER2- pt population. Support: U10CA180821, U10CA180882, U24CA196171, UG1CA189856, U10CA180868 (NRG); NCI BIQSFP, BCRF, Genentech, AstraZeneca. https://acknowledgments.alliancefound.org. Clinical Trials.gov Identifier: NCT01953588 Citation Format: Cynthia X Ma, Vera Suman, A. Marilyn Leitch, Souzan Sanati, Kiran Vij, Gary W Unzeitig, Jeremy Hoog, Mark Watson, Olwen Hahn, Joseph Guenther, Abigail Caudle, Erika Crouch, Horacio Maluf, Amy Tiersten, Monica Mita, Wajeeha Razaq, Tina J Hieken, Yang Wang, Travis Dockter, Jo Anne Zujewski, Anna Weiss, Kelly Hunt, Clifford Hudis, Eric P Winer, Matthew J Ellis, Lisa A Carey, Ann H Partridge. Neoadjuvant chemotherapy (NCT) response in postmenopausal women with clinical stage II or III estrogen receptor positive (ER+) and HER2 negative (HER2-) breast cancer (BC) resistant to endocrine therapy (ET) in the ALTERNATE trial (Alliance A011106) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS4-05.

Pathological complete response to neoadjuvant chemotherapy, but not the addition of carboplatin, is associated with improved survival in Chilean triple negative breast cancer patients: a report of real world data.

BackgroundBreast cancer (BC) is the leading cause of cancer death for Chilean women. About 11% of cases are triple-negative (TN) BC. These are characterised by poor prognosis, higher risk of early recurrence and visceral dissemination versus other BC subtypes. Current standard treatment for early-stage non-metastatic TNBC patients consists of neoadjuvant chemotherapy (NACT) followed by surgery and radiotherapy. Pathological complete response (pCR) to NACT is associated with an increase in survival rates. In general, NACT and adjuvant regimens involve similar cytotoxic drugs. Recent studies have postulated that the use of platinum compounds in TNBC would increase response rates. However, their effects on patient survival remain uncertain.Materials and methodsWe retrieved and analysed medical records from a total of 156 Chilean stage I–III TNBC female patients that received NACT and compared survival rates using carboplatin (Cb)-containing versus non-Cb-containing regimens at two health cancer centres.ResultsMedian age was 51 years (range: 24–81); 13.5% (n = 21) received Cb-containing regimens, 80.1% (n = 125) received sequential anthracyclines plus taxanes; 29.5% (n = 46) of the total group achieved pCR, 28% for the standard treatment and 35% (n = 8) for the Cb-containing group (p = 0.59). We confirmed pCR was associated with prolonged overall survival, invasive and distant disease-free survival (Log-rank p = 0.0236). But the addition of Cb was not associated with differences in survival measures (Log-rank p = 0.5216).ConclusionsTo the best of authors’ knowledge, this is the first report on real-world data in the Chilean population assessing the effect of Cb-containing NACT in TNBC. The authors’ results suggest no survival benefit by the addition of Cb to standard NACT. However, we confirm an increase in survival associated to pCR regardless of treatment.

The Efficacy and Toxicity of Neoadjuvant Chemotherapy Regimens of Epirubicin Plus Cyclophosphamide Followed by Docetaxel or Paclitaxel in Female Breast Cancer Patients

PurposeTo retrospectively analyze the efficacy and toxicity of epirubicin plus cyclophosphamide followed by docetaxel (EC-D) and epirubicin plus cyclophosphamide followed by paclitaxel (EC-P) efficacy as neoadjuvant chemotherapy regiments by pathological complete response (pCR) in this study.MethodsIn total, 455 patients diagnosed with breast cancer who received NAC from January 2014 to January 2019 were enrolled. Of which, 109 patients received EC-D (E: 90, C: 600, D: 80, all in mg/m2) and 346 were treated with EC-P (E: 90, C: 600, D: 175, all in mg/m2). Efficacy of NAC regimens was evaluated by pCR, and the toxicity was studied. Chi-squared test was used at p=0.05.ResultsIn EC-D, 11 patients received ypT0/isN0, and 6 of them got ypT0N0. Analogously, 67 patients receiving received EC-P obtained ypT0/isN0, and 43 people of them acquired ypT0N0. The rate of pCR in EC-P was higher than EC-D. Patients with ER (-), PR (-), Her-2 (+) and high Ki-67 index were easier to were more likely to acquire pCR. Two pCRs were described, the pCR of NAC differed according to the definition. In terms of side effects, there was no significant difference in platelet and urea, but the decrease of hemoglobin and creatinine levels after EC-P treatment was more significant than that after EC-D treatment.ConclusionThe efficacy of EC-P is better than EC-D if pCR is to be determined as a surrogate end-point for prognosis. The patients with anemia or renal insufficiency who need to receive NAC should choose EC-D.

Utilidad de la quimioterapia neoadyuvante en el carcinoma vesical músculo invasivo no metastásico

ObjectiveWe analyzed the profile of patients who were candidates for neoadjuvant chemotherapy (NACT) in stage pT2-4aN0M0, the tolerability and adherence of our cisplatin-based protocol and oncological outcomes. Material and methodsRetrospective observational cohort study including patients diagnosed with muscle-invasive bladder carcinoma treated with NACT. Clinical, histopathological, therapeutic and evolutionary characteristics of the patients were analyzed. The use of NACT was evaluated by the complete response in the surgical specimen (pT0). This and other pathological factors were related to overall survival and progression-free survival. ResultsWe included 90 patients with muscle-invasive bladder carcinoma (clinical stage T2a-T4aN0M0) who received a cisplatin-based NACT regimen between January 2011 and December 2018, prior to radical surgery. Forty percent of patients presented an adverse reaction, with a compliance with the NACT regimen of 92.2%. There were no deaths related to systemic treatment and no adverse reaction to treatment made radical cystectomy impracticable. After performing radical cystectomy, the presence of complete response (pT0) was observed in 20 patients (21%), lower stage in the surgical specimen (<pT2) in 36 patients (40%), positive surgical margins in 7 patients (8%), lymph node involvement (N1) in 16 patients (17.8%). A shorter time to progression was observed in the group of patients who did not achieve a complete pathological response (53 months vs. 83.1 in pT0 patients, P=0.012), in patients with lymph node involvement compared to pN0 (65.4 vs. 28, 2 months, P=0.014) and in those with positive surgical margins compared to those with tumor-free margins (63.5 vs. 8.5 months, P=0.021). ConclusionThe adequate selection of patients with muscle-invasive bladder carcinoma has shown a good tolerance to NACT, with a high compliance rate prior to RC. The improvement in the complete response rate implies a greater survival in this group of patients, with lymph node involvement and positive surgical margins being important prognostic factors.