Efficacy Of Capecitabine Research Articles

Short-term outcomes of a phase II trial of perioperative capecitabine plus oxaliplatin therapy for advanced gastric cancer with extensive lymph node metastases (OGSG1701).

The prognosis of advanced gastric cancer (GC) with extensive lymph node (LN) metastasis treated with surgery alone remains poor. We conducted a multicenter phase II study to evaluate the efficacy and safety of perioperative capecitabine plus oxaliplatin (CapeOx) therapy in patients with advanced GC with extensive LN metastases. Patients with histologically proven HER2-negative or unknown gastric adenocarcinoma with paraaortic LN (PALN) metastases and/or bulky LN metastases located at the celiac axis, common hepatic artery, and/or splenic artery were included in the study. Patients received three cycles of preoperative CapeOx every 3weeks, followed by five cycles of postoperative CapeOx after gastrectomy with D2 or D2 + including PALN dissection. The primary endpoint was the response rate (RR) according to the RECIST v1.0 criteria. Thirty patients from 14 institutions were enrolled from September 2017 to June 2022. Complete response, partial response, stable disease, and progressive disease occurred in zero, 20, eight, and one patient, respectively. One patient was not evaluated. The RR was 66.7% (90% confidence interval, 50.1-80.7%; one-sided P = 0.049). The preoperative chemotherapy completion rate and the curative resection rate were 96.7% and 93.3%, respectively. The minor (grade ≥ 1b) pathological RR was 66.7%. Grade 3 adverse events of preoperative chemotherapy included neutropenia in 3.3%, anemia in 6.7%, and anorexia in 10.0%. One treatment-related death occurred due to postoperative complications. Preoperative CapeOx chemotherapy showed a favorable RR, curative resection rate, and acceptable adverse events in patients with advanced GC with extensive LN metastasis. UMIN000028749 and jRCTs051180186.

Phase II trial evaluating the long-term efficacy and peripheral sensory neuropathy of capecitabine plus oxaliplatin (XELOX) as adjuvant therapy in Japanese patients with operated stage III colon cancer

Adjuvant oxaliplatin plus capecitabine (XELOX) therapy is recommended for patients with curatively resected colon cancer. However, prospective data on its practical application in Japanese patients are limited. Therefore, we aimed to conduct a long-term clinical evaluation of the efficacy and safety of adjuvant XELOX in patients with curatively resected stage III colon cancer (MCSCO-1024). This prospective, multi-center, open-label, single-arm, phase II study enrolled patients with curatively resected stage III colon cancer. The treatment protocol consisted of a 120-minute intravenous infusion of oxaliplatin (130 mg/m2) on day 1 and two divided doses oral capecitabine (2000 mg/m2/day) for 14 days in a 3-week cycle, totaling eight cycles (24 weeks). The primary endpoint was 3-year disease-free survival (DFS), and the secondary endpoints were 5-year overall survival and long-term prognosis of peripheral sensory neuropathy. A total of 196 patients were enrolled between November 2011 and August 2014 (34 months). The 3-year DFS rate was 73%, and the 5-year overall survival rate was 87%. The overall incidence of peripheral sensory neuropathy was 17%, with a 1% rate of grade 3 neuropathy after 5 years. Adjuvant XELOX demonstrated utility and safety in the clinical management of Japanese patients with stage III colon cancer.

Circulating tumor DNA status and dynamics predict recurrence in patients with resected extrahepatic cholangiocarcinoma

Background & AimsSurgery is the only curative therapeutic option for resectable extrahepatic cholangiocarcinoma (eCCA), but recurrence is common, and prognosis is poor. There is an unmet clinical need for improved decision-making regarding adjuvant chemotherapy (ACT). Here we evaluated the usefulness of monitoring longitudinal circulating tumor DNA (ctDNA) for minimal residual disease (MRD) in patients of the STAMP trial, which compares the efficacy of adjuvant capecitabine (CAP) versus gemcitabine plus cisplatin (GemCis). MethodsBetween July 2017 and November 2020, 101 patients were randomized 1:1 to receive GemCis (n=50) or CAP (n=51). Efficacy outcomes were analyzed with an extended follow-up of 19 months from the previous report. From a biomarker cohort of 89 patients, longitudinal plasma samples (n=254) were prospectively collected post-surgery before adjuvant chemotherapy (ACT), and on-ACT at 12 and 24 weeks from cycle 1 day 1 (C1D1). ctDNA was evaluated using a personalized, tumor-informed, 16-plex PCR-NGS assay and was correlated with clinical outcomes. ResultsIn the extended follow-up analysis, median disease-free survival (DFS) and overall survival (OS) did not significantly differ between the CAP and GemCis groups. Significantly inferior DFS was associated with ctDNA-positivity before ACT (HR, 1.8; p=0.029), on-ACT at 12 weeks from C1D1 (HR, 7.72; p<0.001), on-ACT at 24 weeks from C1D1 (HR, 5.24; p<0.001), and anytime post-surgery (HR, 3.81; p<0.001). Analysis of pre-treatment to on-treatment ctDNA dynamics revealed that serially ctDNA-negative patients exhibited a significantly longer DFS compared to those with sustained ctDNA-positivity (HR, 6.7; p<0.001) or who turned ctDNA-positive (HR, 5.8; p<0.001). ConclusionIn patients with resected eCCA, ctDNA status and dynamics predicted recurrence during adjuvant therapy, and may help optimize clinical decision-making. Impact and implicationsThe findings from this study highlight the critical role of ctDNA as a prognostic biomarker and monitoring tool for patients with resected extrahepatic cholangiocarcinoma (eCCA). By demonstrating the superiority of ctDNA to predict disease recurrence compared to conventional biomarkers such as CA 19-9 and CEA, this study underscores its potential in guiding decision-making during adjuvant chemotherapy. These results may be crucial to refine post-surgical treatment strategies and improve patient outcomes. The practical application of ctDNA monitoring could lead to more personalized treatment approaches, enabling timely interventions based on minimal residual disease (MRD) status. Clinical Trial Registration numberNCT03079427

Efficacy of pyrotinib and capecitabine in recurrent breast cancer with a HER2-negative genetic switch following systemic therapy: A case report and literature review

Despite the demonstrated safety and efficacy of pyrotinib and capecitabine in treating human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer, their efficacy in recurrent breast cancer in which the HER2 status has changed to negative remains unexplored. Here, we report a case of a 38-year-old female diagnosed with invasive ductal adenocarcinoma of the left breast, staged as mcT2N0M0. Fluorescence in situ hybridization (FISH) confirmed that the tumor was hormone receptor (HR) positive with low HER2 expression (2+) and a HER2/CEP17 ratio of 3.56. Following neoadjuvant targeted therapy and chemotherapy, she underwent a modified radical mastectomy. Post-surgical histopathological examination revealed a non-pathological complete response, classified as ypT1cypN1M0. The tumor remained HR positive with low HER2 expression (2+), but the FISH result was negative (HER2/CEP17 ratio of 1.65). For 1 year, she was administered dual-targeted therapy with goserelin and exemestane. Sequential therapy with neratinib was initiated; however, it was discontinued due to grade IV diarrhea. Despite ongoing endocrine therapy, she experienced tumor recurrence on the left chest wall. A biopsy of the recurrent lesion revealed it to be HR positive with low HER2 expression (2+) and a negative FISH result (HER2/CEP17 ratio of 1.33). The recurrent lesion responded to combination therapy consisting of pyrotinib and capecitabine, with tolerable adverse events. This case highlights the potential advantages of combining pyrotinib and capecitabine when the HER2 status changes to negative following systemic therapy.

P90-6 Efficacy and safety of neratinib and capecitabine in HER2-positive metastatic breast cancer: a systematic review

P90-6 Efficacy and safety of neratinib and capecitabine in HER2-positive metastatic breast cancer: a systematic review

Efficacy and Safety of Metronomic Capecitabine in Hepatocellular Carcinoma: ASystematic Review and Meta-analysis.

Metronomic capecitabine has been found to be useful in several types of cancers such as pancreatic cancer, breast cancer, gastrointestinal cancers, nasopharyngeal carcinoma, and metastatic colorectal cancer. This unique systematic literature review and meta-analysis was undertaken to assess the effectiveness and safety of metronomic capecitabine as a treatment regimen for hepatocellular carcinoma. A systematic search of major databases was performed. Eight studies that dealt with the use of metronomic capecitabine for hepatocellular carcinoma (HCC) were selected, seven were non-randomized control trials (n-RCTs), and one was a randomized control trial (RCT). Meta-analysis of these studies was performed using Review Manager v5.3 and STATA 15.1 software. The pooled prevalence of overall survival (OS), progression-free survival (PFS), overall response rate (ORR), grade 1-2 adverse events (grade 1-2 AEs), grade 3-4 adverse events (grade 3-4 AEs) was determined, including publication bias and sensitivity analysis. Eight studies met the inclusion criteria, combining the pooled data of 476 patients from safety and efficacy studies. The pooled prevalence of disease control rate (DCR) and overall response rate (ORR) achieved with metronomic capecitabine was 36% (95% CI 32-41) and 7% (95% CI 5-9) respectively. The median progression-free survival (PFS) and median overall survival (OS) were 3.57months (95% CI 3.29-3.85) and 11.75months (95% CI 10.56-12.95) respectively. The incidence of grade 3-4 adverse events (grade 3-4 AEs) and grade 1-2 adverse events (grade 1-2 AEs) was 38% (95% CI 32-44) and 73% (95% CI 67-79) respectively. This meta-analysis highlights metronomic capecitabine as a potential treatment for hepatocellular carcinoma (HCC) in the advanced stage. However, effective management of capecitabine's side effects is essential.

Nab-paclitaxel plus capecitabine as first-line treatment for advanced biliary tract cancers: An open-label, non-randomized, phase II clinical trial.

Biliary tract cancers (BTCs) are a heterogeneous group of tumors with high malignancy, poor prognosis, and limited treatment options. To explore the efficacy and safety of nab-paclitaxel plus capecitabine as first-line treatment for advanced and metastatic BTCs. This open-label, non-randomized, double-center, phase II clinical trial recruited systemic therapy-naive patients with unresectable or metastatic BTCs between April 2019 and June 2022 at Beijing Cancer Hospital and the First Hospital of China Medical University. Eligible patients were administered nab-paclitaxel (150 mg/m2, day 1) and capecitabine (2000 mg/m2, twice daily, days 1-7) in 14-day cycles until experiencing intolerable toxicity or disease progression. The primary outcome was the objective response rate (ORR). The secondary outcomes included the disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and safety. A total of 44 patients successfully completed the trial, with a median age of 64.00 years (interquartile range, 35.00-76.00), and 26 (59.09%) were females. Tumor response assessment was impeded for one patient due to premature demise from tumor hemorrhage. Among the remaining 43 patients undergoing at least one imaging assessment, the ORR was 23.26% [95% confidence interval (CI): 11.80%-38.60%], and the DCR was 69.77% (95%CI: 53.90%-82.80%). The median OS was 14.1 months (95%CI: 8.3-19.9), and the median PFS was 4.4 months (95%CI: 2.5-6.3). A total of 41 patients (93.18%) experienced at least one adverse event (AE), with 10 patients (22.73%) encountering grade ≥ 3 AEs, and the most frequent AEs of any grade were alopecia (79.50%), leukopenia (54.55%), neutropenia (52.27%), and liver dysfunction (40.91%), and no treatment-related deaths were documented. Nab-paclitaxel plus capecitabine may be an effective and safe first-line treatment strategy for patients with advanced or metastatic BTCs.

Clinical effect analysis of different regimens of capecitabine in the treatment of patients with advanced colon cancer

To assess the efficacy and safety of capecitabine in treating advanced colon cancer. Patients with advanced colon cancer were randomized into three groups: control group (n = 50, daily dose 2,500 mg/m2), the medium-dose group (n = 50, daily dose 2,000 mg/m2), and the low-dose group (n = 50, daily dose 1,500 mg/m2) capecitabine for 4 cycles(12 weeks). Afterwards, the response rate, quality of life, and adverse reactions of the three groups were collected for comparison. Efficacy rates were 50%, 70%, and 72%, respectively, with the low-dose group showing the highest efficacy (χ2 = 6.424, p = 0.040); Quality of life comparison results indicated significant differences in physical function (F = 98.528, p < 0.001), role function (F = 123.418, p < 0.001), social function(F = 89.539, p < 0.001), emotional function (6 F = 77.295, p < 0.001), cognitive function (F = 83.529, p < 0.001), and overall quality of life (F = 99.528, p < 0.001) among the three groups, and the three groups returned consistent scores, with the low-dose group scoring highest. Incidence rates were 86.00%, 46.00%, 34.00%, with the control group having the highest rate (χ2 = 16.505, p < 0.001). Capecitabine at a dosage of 1,500 mg/m2 demonstrated a good therapeutic effect and improved the quality of life in patients with advanced colon cancer, with a lower incidence of adverse reactions. A prolonged treatment cycle with reduced dosage is suggested to further improve treatment outcomes and patient prognosis. Trial registration The study was registered on clicaltrials.gov ‘NCT06246461’ on 30/01/2024.

Capecitabine or Capecitabine Plus Oxaliplatin Versus Fluorouracil Plus Cisplatin in Definitive Concurrent Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma (CRTCOESC): A Multicenter, Randomized, Open-Label, Phase 3 Trial.

This phase 3 trial aimed to compare the efficacy and safety of capecitabine or capecitabine plus oxaliplatin (XELOX) with those of fluorouracil plus cisplatin (PF) in definitive concurrent chemoradiotherapy (DCRT) for inoperable locally advanced esophageal squamous cell carcinoma (ESCC). Patients were randomly assigned to receive two cycles of capecitabine, XELOX, or PF along with concurrent intensity-modulated radiation therapy. Patients in each arm were again randomly assigned to receive two cycles of consolidation chemotherapy or not. The primary end points were 2-year overall survival (OS) rate and incidence of grade ≥3 adverse events (AEs). A total of 246 patients were randomly assigned into the capecitabine (n = 80), XELOX (n = 85), and PF (n = 81) arms. In capecitabine, XELOX, and PF arms, the 2-year OS rate was 75%, 66.7%, and 70.9% (capecitabine v PF: hazard ratio [HR], 0.91 [95% CI, 0.61 to 1.35]; nominal P = .637; XELOX v PF: 0.86 [95% CI, 0.58 to 1.27]; P = .444); the median OS was 40.9 (95% CI, 34.4 to 49.9), 41.9 (95% CI, 28.6 to 52.1), and 35.4 (95% CI, 30.4 to 45.4) months. The incidence of grade ≥3 AEs during the entire treatment was 28.8%, 36.5%, and 45.7%, respectively. Comparing the consolidation chemotherapy with the nonconsolidation chemotherapy groups, the median OS was 41.9 (95% CI, 34.6 to 52.8) versus 36.9 (95% CI, 28.5 to 44) months (HR, 0.71 [95% CI, 0.52 to 0.99]; nominal P = .0403). Capecitabine or XELOX did not significantly improve the 2-year OS rate over PF in DCRT for inoperable locally advanced ESCC. Capecitabine showed a lower incidence of grade ≥3 AEs than PF did.

Capecitabine monotherapy as first-line treatment in advanced HER2-normal breast cancer - a nationwide, retrospective study.

The study utilized the Danish Breast Cancer Group (DBCG) database and was conducted retrospectively across all Danish oncology departments. Inclusion criteria were female patients, with HER2-normal advanced breast cancer treated with capecitabine monotherapy as the first-line treatment from 2010 to 2020. The primary endpoints were overall survival (OS) and progression-free survival (PFS). A total of 494 patients were included. Median OS was 16.4 months (95% confidence interval [CI]: 14.5-18.0), and median PFS was 6.0 months (95% CI: 5.3-6.7). Patients with estrogen receptor (ER)-positive disease had significantly longer OS (median: 22.8 vs. 10.5 months, p < 0.001) and PFS (median: 7.4 vs. 4.9 months, p = 0.003), when compared to ER-negative patients. Stratifying by age, patients under 45 years displayed a median PFS of 4.1 months, while those aged 45-70 years and over 70 years had median PFS of 5.7 and 7.2 months, respectively (p = 0.01). In this nationwide study, the efficacy of capecitabine as a first-line treatment for HER2-normal advanced breast cancer is consistent with other, mainly retrospective, studies. However, when assessed against contemporary and newer treatments, its effectiveness appears inferior to alternative chemotherapies or targeted therapies.

QUATTRO-II randomized trial: CAPOXIRI+bevacizumab vs. FOLFOXIRI+bevacizumab as first-line treatment in patients with mCRC

The QUATTRO-II trial examined the efficacy and safety of capecitabine+oxaliplatin+irinotecan (CAPOXIRI)+bevacizumab (BEV) vs. 5-fluorouracil+folinic acid+oxaliplatin+irinotecan (FOLFOXIRI)+BEV in metastatic colorectal cancer (mCRC). In this phase II study (ClinicalTrials.gov: NCT04097444; jRCTs041190072), patients were randomized (1:1) to FOLFOXIRI+BEV or CAPOXIRI+BEV. The induction treatment in the FOLFOXIRI+BEV/CAPOXIRI+BEV arms was continued for 8/6 cycles (maximum 12/8 cycles if feasible), and the maintenance treatment was 5-fluorouracil/leucovorin+BEV or capecitabine+BEV at the investigators' discretion. The primary endpoint was progression-free survival (PFS), with the two arms deemed equivalent if the hazard ratio (HR) of the point estimate was 0.80<HR<1.25. Secondary endpoints were overall response rate (ORR), overall survival (OS), incidence of adverse events (AEs), and patient-reported outcomes. Overall, 51 and 52 patients were randomized to FOLFOXIRI+BEV and CAPOXIRI+BEV, respectively. The study met itsprimary endpoint; PFS at median follow-up of 23.7 months was 10.6 months (95% confidence interval [CI], 7.7-13.3) in the FOLFOXIRI+BEV arm vs. 10.9months (95% CI, 9.3-14.3) in the CAPOXIRI+BEV arm (HR1.114 [0.80<HR<1.25], p= 0.654). In the FOLFOXIRI+BEV vs. CAPOXIRI+BEV arms, the 2-year OS rate (95% CI) was 65.5% (49.5%-77.6%) vs. 74.3% (59.8%-84.2%), and the ORR (95% CI) was 76.5% (62.5%-87.2%) vs. 84.6% (71.9%-93.1%). Major (grade ≥3) AEs in the FOLFOXIRI+BEV vs. CAPOXIRI+BEV arms were neutropenia (68.6% vs. 40.4%), febrile neutropenia (9.8% vs. 11.5%), diarrhea (7.8% vs. 17.3%), and appetite loss (7.8% vs. 17.3%). CAPOXIRI+BEV was well tolerated with reduced hematological toxicity and efficacy comparable to those of FOLFOXIRI+BEV, providing a potentially convenient first-line treatment alternative to FOLFOXIRI+BEV in patients with mCRC. Chugai Pharmaceutical Co., Ltd.

46P Efficacy and safety of fruquintinib plus capecitabine as first-line treatment in patients (pts) with advanced metastatic colorectal cancer (mCRC) ineligible for intravenous chemotherapy: Early outcome report of a two-stage, single armed, phase II study

46P Efficacy and safety of fruquintinib plus capecitabine as first-line treatment in patients (pts) with advanced metastatic colorectal cancer (mCRC) ineligible for intravenous chemotherapy: Early outcome report of a two-stage, single armed, phase II study

Efficacy and safety of concurrent capecitabine and radiotherapy as adjuvant treatment in triple negative breast cancer.

e12534 Background: Triple-negative breast cancer remains a very aggressive disease with few treatments option. Neoadjuvant dose dense chemotherapy, adjuvant therapy with capecitabine for residual disease and radiotherapy are standard treatments. The aims of this study were to evaluate the efficacy and safety of capecitabine concurrent with radiotherapy in initially clinical stage III patients with triple negative breast cancer in order to improve locoregional control and survival of these patients. Methods: We prospectively analyzed 24 patients with triple negative breast cancer with residual disease after dose dense neoadjuvant chemotherapy with Epirubicin and Cyclophosphamide and Docetaxel (in some cases with carboplatin) who received concurrent Capecitabine and radiotherapy in adjuvant setting. External beam radiotherapy to the hole breast was administered at a dose of 45–50.4 Gy in 25–28 fractions, concurrent with Capecitabine 825 mg/m2, 5 days/week. Results: Median age at diagnostic was 47.1±7.4. Stage distribution was as followed: 45.8% stage IIIA, 25% stage IIIB and 29.2% stage IIIC. Median follow-up was 31 months. Median Disease-Free Survival (DFS) was 48 months, with 76%, 68%, and 46% of patients without recurrence at 24, 36 and 48 months respectively. All patients presented with distant relapses. Median overall survival (OS) was not reached, and 3 years survival rate was 88%. Most common toxicities of concurrent radiotherapy and capecitabine were radiation dermatitis all grades in 100% of patients, grade 3 in 37.5% and grade 4 in 4.1%. Other side effects were neutropenia grade 4 in 8.3% and lymphopenia grade 4 in 45.8% of patients. Conclusions: Capecitabine concurrent with radiotherapy appears to be very efficacious and safe in the adjuvant treatment of breast cancer, especially in preventing local recurrence.

Adjuvant tislelizumab combined with capecitabine for patients with biliary tract cancer with high risk of postoperative relapse (ACTIVE): Primary analysis from a prospective cohort study.

e16248 Background: Only 20% of biliary tract cancer (BTC) patients are eligible for surgical resection with curative intent, with 5-year overall survival of less than 10% for all patients. This rate is even lower in patients with high-risk features. Capecitabine as an adjuvant therapy in biliary tract cancer has been verified to improve overall survival, however, the efficacy still remains limited. PD-1/L1 antibody combined with chemotherapy have been demonstrated to improve survival in advanced biliary tract cancer. This study aimed to evaluate the efficacy and safety of adjuvant tislelizumab and capecitabine following surgery for biliary tract cancer with high risk of recurrence. Methods: This was a single-center, prospective cohort phase II study. BTC patients (pts) underwent R0/R1 resection with high postoperative recurrence risk were eligible. The high-risk factors included positive resection margins, positive lymph nodes, positive perineural invasion, and tumor &gt; 5cm in diameter. The patients were divided into two groups, the tislelizumab (TIS 200 mg Q3W for 1 year )+capecitabine (CAP D1-14, 1500mg/m2 for eight 3-weekly cycles) group and the capecitabine group. The primary endpoint was DFS (disease free survival). The second endpoints was OS (overall survival) and adverse event (AE). Results: A total of 37 pts were enrolled into the study, while 22 pts in the TIS+CAP group and 15 in CAP group, 23 males and 14 females with a median age of 66 years. According to the location of the tumor, 37.8% pts were intrahepatic cholangiocarcinoma, 21.6% were gallbladder cancer, 5.4% were distal cholangiocarcinoma and 35.1% were hilar cholangiocarcinoma. The median DFS was 16.2 months (95% CI, 8.1-26.2) in the TIS+CAP group, which was longer than CAP group (11.4 months, 95% CI 4.2-27.1). 12-month RFS rates were 56.5% and 36.6% , respectively. The most common adverse events (AEs, any grade) were rash (18.2%), vomiting (13.6%), neutropenia (13.6%) and anorexia (13.6%) in the TIS+CAP group. Conclusions: Tislelizumab in combination with capecitabine were effective and safe as adjuvant therapy, which can prolong the DFS of BTC patients with high recurrence risk after resection. Clinical trial information: NCT04782804 .

Non-basal subtype defined by FOXC1 expression as an independent predictor of capecitabine efficacy in the triple negative breast cancer GEICAM/2003-11_CIBOMA/2004-01 trial.

516 Background: In a prespecified correlative analysis of the GEICAM/2003-11_CIBOMA/2004-01 phase III clinical trial (CIBOMA trial), PAM50 non-basal status identified triple-negative breast cancer (TNBC) patients (pts) most likely to benefit from adjuvant capecitabine (cap). FOXC1 cell plasticity/metastasis transcriptional driver assessment by standardized Veresca FOXC1 Immunohistochemistry (IHC) BC test (Veresca) has shown rigorous capacity to identify basal-like breast cancer (BLBC) subtype throughout TNBC cohorts. We sought to explore the concordance of BLBC identification by FOXC1 with PAM50 molecular subtyping and its prognostic/predictive value in the CIBOMA trial (NCT00130533). Methods: We analyzed FOXC1 expression (Veresca, Onconostic Technologies) and the Ki-67 Antigen MIB-1 (Dako) by IHC on tumors from 705 TNBC pts randomized to maintenance with cap (357, 51%) vs observation (obs) (348, 49%) after standard (neo)adjuvant chemotherapy (CT). Veresca score (VFOXC1) was defined as % of tumor cells with positive nuclear staining (Proportion Score 0-5) plus staining intensity (Intensity Score 0-3). BLBC subtyping by Veresca (cutoff ≥4) and PAM50 signature (Nanostring) were compared using ROC analysis and Kappa index (KI). Ki67 ≥20% cutoff was applied. Cox regression models were assessed to predict DRFS (primary endpoint), DFS and OS (secondary endpoints). Results: VFOXC1≥4 identified 460 (65%) BLBC pts in this CIBOMA trial cohort (229 (49.8%) treated with cap, and 231 (50.2%) in obs). VFOXC1 detection was not associated with any clinicopathological characteristic. VFOXC1 expression significantly correlated with PAM50 BLBC subtyping (ROC analysis AUC 0.874, KI 0.43) but moderately with IHC subtyping (AUC 0.548). VFOXC1 BLBC subtype was not associated with DRFS (HR=0.94; 95%CI 0.68-1.30; p=0.713) in the entire cohort. However, VFOXC1 non-BLBC subtype was a strong independent predictor of cap benefit for DRFS (univariate analysis, interaction p-value p=0.117; HR=0.53; 95%CI 0.31-0.90; p=0.019; multivariate analysis, HR=0.44; 95%CI 0.25–0.76; p=0.003). This predictive effect of VFOXC1 non-BLBC on cap benefit was also confirmed at DFS (HR=0.47; 95%CI 0.28–0.78; p=0.003) and OS (HR=0.48; 95%CI 0.24–0.96; p=0.038), and was independent of Ki67 proliferation status (multivariate DRFS; Ki67&lt;20%, HR=0.41; 95%CI 0.20-0.82; p=0.012; Ki67≥20%, HR=0.31; 95%CI 0.10-0.97; p=0.045). VFOXC1 non-BLBC subtype had no association with clinical outcome in obs arm. Conclusions: In the CIBOMA TNBC trial, the non-BLBC definition by a single biomarker (FOXC1 Veresca) provided prognostic and predictive value of cap benefit after (neo)adjuvant CT, corroborating our previous findings by PAM50 and IHC non-BLBC subtyping. This is a pragmatic option to effectively apply findings from this trial in the real-world setting. Clinical trial information: NCT00130533 .

Real-world efficacy and safety of capecitabine with oxaliplatin in patients with advanced adenocarcinoma of the ampulla of Vater

BackgroundAdenocarcinoma of the ampulla of Vater (AoV) is one of the rare periampullary cancers, and due to its anatomical location, it is categorized into various histologic subtypes. Its rarity and diversity pose challenges in treatment decision-making for patients with advanced AoV carcinoma. This study investigated the efficacy and safety of the combined regimen of capecitabine and oxaliplatin (CAPOX) in a real-world clinical setting.MethodsThis investigation encompassed patients with advanced AoV carcinoma who underwent CAPOX treatment. Histologic phenotypes were identified through a combination of histopathological analysis and protein expression markers, including MUC1, CDX2, CK20, and MUC2. The correlation between histopathological determinants and survival outcomes was explored, in addition to an evaluation of the safety profile of CAPOX therapy.ResultsFrom January 2010 to June 2023, 42 patients received CAPOX. Of these, 14 patients (33.3%) had not received any prior palliative chemotherapy, while 28 patients (66.7%) had undergone one prior line of chemotherapy. At a median follow up of 9.0 months, the median progression-free survival (PFS) was 4.38 months (95% CI, 2.78–5.69) and the median overall survival (OS) was 9.57 months (95% CI 7.56–11.6). The objective response and disease control rates were 38.1% and 61.9%, respectively. Patients who received CAPOX as a second-line treatment had poorer PFS (HR = 2.62; 95% CI, 1.49–4.90, p = 0.003) and OS (HR = 2.82, 95% CI, 1.47–5.38, p = 0.001) compared to those who received CAPOX as a first-line chemotherapy. There were no statistically significant differences in PFS (p = 0.185) and OS (p = 0.097) between groups based on histologic subtypes. Neutropenia (14.3%) emerged as the predominant grade 3–4 toxicity. Notably, treatment cessation occurred in select instances owing to grade 3 fatigue (9.5%) and peripheral neuropathy (9.5%).ConclusionsThis study confirmed the therapeutic efficacy and safety of CAPOX in a real-world setting, consistent with prior phase II trial results. While CAPOX proved feasible for advanced AoV carcinoma regardless of histologic subtype, its reduced effectiveness in second-line settings necessitates further research to determine its optimal palliative use.

A phase I/II study of nintedanib and capecitabine for refractory metastatic colorectal cancer.

Nintedanib is a tyrosine kinase inhibitor with efficacy in bevacizumab-resistant colorectal cancer models. This phase I/II study evaluated the recommended phase II dose and efficacy of nintedanib and capecitabine in refractory metastatic colorectal cancer. Key eligibility criteria included refractory metastatic colorectal cancer and ECOG performance status of 1 or lower. The primary endpoint was 18-week progression-free survival (PFS). A 1-sided binomial test (at α = .1) compared the observed 18-week PFS with a historic control of .25. Forty-two patients were enrolled, including 39 at the recommended phase II dose. The recommended phase II dose was established to be nintedanib 200 mg by mouth twice daily and capecitabine 1000 mg/m2 by mouth twice daily. The protocol was evaluated for efficacy in 36 patients. The 18-week PFS was 42% (15/36 patients; P = .0209). Median PFS was 3.4 mo. Median overall survival was 8.9 mo. Sixteen (44%) patients experienced a grade 3/4 adverse event, most commonly fatigue (8%), palmoplantar erythrodysesthesia (8%), aspartate aminotransferase elevation (6%), asthenia (6%), pulmonary embolus (6%), and dehydration (6%). Osteopontin levels at cycle 1, day 1 and cycle 3, day 1 as well as ΔCCL2 levels correlated to disease control at 18 weeks. The combination of nintedanib and capecitabine is well tolerated. Clinical efficacy appears to be superior to regorafenib or tipiracil hydrochloride monotherapy. Further investigation of similar combinations is warranted. NCT02393755.

Efficacy of adjuvant capecitabine in residual triple negative breast cancer: a multicenter observational Turkish Oncology Group (TOG) study

ABSTRACT Background Triple negative breast cancer (TNBC) is characterized by high rates of recurrence, especially in patients with residual disease after neoadjuvant chemotherapy (NAC). Capecitabine is being used as standard adjuvant treatment in residual TNBC. We aimed to investigate the real-life data regarding the efficacy of capecitabine in residual TNBC. Design and methods In this retrospective multicenter study, TNBC patients with residual disease were evaluated. Patients, who received standard anthracycline and taxane-based NAC and adjuvant capecitabine were eligible. Overall survival (OS), disease free survival (DFS) and toxicity were analyzed. Results 170 TNBC patients with residual disease were included. Of these, 62.9% were premenopausal. At the time of analysis, the recurrence rate was 30% and death rate was 18%. The 3-year DFS and OS were 66% and 74%, respectively. In patients treated with adjuvant capecitabine, residual node positive disease stood out as an independent predictor of DFS (p = 0.024) and OS (p = 0.032). Undergoing mastectomy and the presence of T2 residual tumor was independent predictors of DFS (p = 0.016) and OS (p = 0.006), respectively. Conclusion The efficacy of capecitabine was found lower compared to previous studies. Selected patients may have further benefit from addition of capecitabine. The toxicity associated with capecitabine was found lower than anticipated.

Toripalimab plus capecitabine in the treatment of patients with residual nasopharyngeal carcinoma: a single-arm phase 2 trial

Patients with residual nasopharyngeal carcinoma after receiving definitive treatment have poor prognoses. Although immune checkpoint therapies have achieved breakthroughs for treating recurrent and metastatic nasopharyngeal carcinoma, none of these strategies have been assessed for treating residual nasopharyngeal carcinoma. In this single-arm, phase 2 trial, we aimed to evaluate the antitumor efficacy and safety of toripalimab (anti-PD1 antibody) plus capecitabine in patients with residual nasopharyngeal carcinoma after definitive treatment (ChiCTR1900023710). Primary endpoint of this trial was the objective response rate assessed according to RECIST (version 1.1). Secondary endpoints included complete response rate, disease control rate, duration of response, progression-free survival, safety profile, and treatment compliance. Between June 1, 2020, and May 31, 2021, 23 patients were recruited and received six cycles of toripalimab plus capecitabine every 3 weeks. In efficacy analyses, 13 patients (56.5%) had complete response, and 9 patients (39.1%) had partial response, with an objective response rate of 95.7% (95% CI 78.1-99.9). The trial met its prespecified primary endpoint. In safety analyses, 21 of (91.3%) 23 patients had treatment-related adverse events. The most frequently reported adverse event was hand-foot syndrome (11 patients [47.8%]). The most common grade 3 adverse event was hand-foot syndrome (two patients [8.7%]). No grades 4-5 treatment-related adverse events were recorded. This phase 2 trial shows that combining toripalimab with capecitabine has promising antitumour activity and a manageable safety profile for patients with residual nasopharyngeal carcinoma.

A retrospective analysis of the efficacy and safety of capecitabine plus oxaliplatin (CapeOX) and docetaxel plus S-1 (DS) as adjuvant chemotherapy for pathological stage III (p stage III) gastric cancer (GC).

342 Background: Adjuvant chemotherapy following surgical resection is the standard treatment for patients with p stage III GC in Japan. Although CapeOX and DS are available for adjuvant chemotherapy for stage III GC, there is limited data on which treatment is more effective. We aim to compare the efficacy and safety of CapeOX and DS as adjuvant chemotherapy in patients with p stage III GC. Methods: We extracted data of patients with p stage III GC who received either CapeOX (capecitabine on days 1–14 plus oxaliplatin on day1 for 8 cycles [q 3week]) or DS (S-1 on days 1–14 at 1st cycle [q 3 week], docetaxel on day 1 plus S-1 on days 1–14 during 2–7 cycles [q 3 week], and S-1 on days 1–28 up to 1 year [q 6 week]) as adjuvant chemotherapy after surgical resection at our institution from February 2016 to May 2022. Three-year relapse-free survival (RFS) and adverse events (AEs) were assessed. Cox proportional hazard model was used in multivariable analysis to assess the effect of independent variables on RFS. Results: A total of 74 patients were included in this study (CapeOX 31/ DS 43). Patient characteristics (CapeOX/DS) were as follows: median age, 60/64 years; male, 77/65 %; ECOG-PS 0/1, 45%/44%, 55%/56 %; p stage IIIA/IIIB/IIIC, 10%/30%, 48%/51 %, 42%/19 %. The 3-year RFS was 37% in the (hazard ratio [HR] = 0.81, P=0.48). For p stage IIIA, IIIB, and IIIC, the 3-year RFS in the CapeOX group and the DS group was 67% vs. 75% (HR = 0.56, P =0.52), 43% vs. 42% (HR = 1.11, P =0.81), and 23% vs. 0% (HR = 1.59, P =0.39), respectively. Multivariable analysis adjusted for p stage showed no significant differences in RFS between the CapeOX group and the DS group (HR=1.06, P=0.85). Compared to DS, CapeOX was associated with lower incidences of febrile neutropenia (0% vs 7%) and alopecia (6% vs 74%), and a higher incidence of peripheral neuropathy (80% vs 23%). Conclusions: This analysis indicates that CapeOX and DS have comparable efficacy as adjuvant chemotherapy for p stage III GC in terms of RFS, albeit with different profiles of AEs.