Capecitabine Maintenance Therapy Research Articles

Capecitabine maintenance therapy in metastatic colorectal cancer patients with no evidence of disease: CAMCO trial.

Background: In patients with metastatic colorectal cancer (mCRC) exhibiting no evidence of disease (NED), this study assessed the efficacy and safety of capecitabine maintenance therapy. Methods: The single-arm, phase II CAMCO trial enrolled mCRC-NED patients after first-line treatment, administering oral capecitabine maintenance for 1year. Results: A total of 93 patients were enrolled. The primary endpoint, 3-year disease-free survival, yielded a rate of 51.6% (95% CI: 41.3-62.0%). Secondary endpoints included a 3-year overall survival rate of 83.9% (95% CI: 76.3-91.5%). Grade 3 adverse events (AE) were observed in sevenpatients (7.5%). Predominantly grade 1 and 2, the most common AE was hand-foot syndrome. Conclusion: In mCRC-NED patients, capecitabine maintenance demonstrated a manageable 3-year disease-free survival rate of 51.6%, accompanied by manageable AEs. Clinical Trial Registration: NCT01880658 (ClinicalTrials.gov).

Cost-effectiveness analysis of capecitabine maintenance therapy plus best supportive care vs. best supportive care alone as first-line treatment of newly diagnosed metastatic nasopharyngeal carcinoma.

Maintenance therapy with capecitabine after induction chemotherapy for patients with newly diagnosed metastatic nasopharyngeal carcinoma (mNPC) has been confirmed to be effective. This study aimed to evaluate the cost-effectiveness of capecitabine as maintenance therapy for patients with mNPC from the Chinese payers' perspective. Markov model was conducted to simulate the disease progress and evaluated the economic and health outcomes of capecitabine maintenance plus best-supported care (CBSC) or best-supported care (BSC) alone for patients with mNPC. Survival data were derived from the NCT02460419 clinical trial. Costs and utilities were obtained from the standard fee database and published literature. Measured outcomes were total costs, quality-adjusted life-years (QALYs), life-years (LYs), incremental cost-utility ratios (ICURs), incremental cost-effectiveness ratios (ICERs), incremental net monetary benefit (INMB), and incremental net-health benefit (INHB). Sensitivity analyses were performed to assess model robustness. Additional subgroup cost-effectiveness analyses were accomplished. Throughout the course of the disease, the CBSC group provide an incremental cost of $9 734 and additional 1.16 QALYs (1.56 LYs) compared with the BSC group, resulting in an ICUR of $8 391/QALY and ICER of $6 240/LY. Moreover, the INHB was 0.89 QALYs, and the INMB was $32 034 at the willingness-to-pay threshold of $36 007/QALY. Subgroup analyses revealed that CBSC presented a positive trend of gaining an INHB in all subgroups compared with the BSC group. The results of sensitivity analyses supported the robustness of our model. Compared with BSC, after induction chemotherapy, CBSC as a first-line treatment was cost-effective for newly diagnosed mNPC. These results suggest capecitabine maintenance therapy after induction chemotherapy as a new option for patients with newly diagnosed mNPC.

A cost-effectiveness analysis of capecitabine maintenance therapy versus routine follow-up for early-stage triple-negative breast cancer patients after standard treatment from a perspective of Chinese society

BackgroundCapecitabine maintenance therapy is safe and efficacious for early-stage triple-negative breast cancer (TNBC) patients, but the cost-effectiveness of its long-term use has not been investigated. Here, we evaluated the cost-effectiveness of capecitabine maintenance therapy, compared with routine follow-up, in early-stage TNBC patients after standard treatment from a perspective of Chinese society.MethodsA three-state Markov model based on the data from the SYSUCC-001 trial was constructed to estimate the cost-effectiveness of capecitabine maintenance therapy in a month cycle over a period of 30-year time horizon. A 5% annual discount rate was set for all costs and benefits. One-way and probabilistic sensitivity analyses were performed to explore the model uncertainties. The main outcomes include quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), and the number needed to treat (NNT) to prevent one additional event.ResultsCompared with routine follow-up, 1-year capecitabine maintenance therapy yielded an additional 1.29 quality-adjusted life years (QALYs) at an additional cost of $3391.70, with an ICER of $2630.53 (95% CI: $1159.81–$5090.12) per QALY gained. The ICER was considerably lower than the recommended willingness-to-pay (WTP) threshold (i.e., $28,130.00 per QALY). The results were sensitive to the discount rate, drug cost, and treatment cost after relapse. Further, the NNT to prevent one additional relapse case was 29.2 (95% CI: 13.2–196.6), 16.7 (95% CI: 8.4–111.6), and 12.0 (95% CI: 5.7–82.6) at 1, 2, and 5 years, respectively.ConclusionsOne-year capecitabine maintenance therapy for early-stage TNBC after standard treatment, compared with routine follow-up, was found to be highly cost-effective with promising clinical benefits and acceptable increased costs. Real-world studies are warranted to validate our findings in the future.

The prognosis and risk factors for capecitabine maintenance treatment in metastatic breast cancer: a retrospective comparative cohort study.

BackgroundMaintenance treatment following efficient chemotherapy can improve the treatment outcomes of patients with metastatic breast cancer (MBC). However, there are no studies for identifying the prognostic factors for patients who could benefit from capecitabine maintenance. Therefore, this study aimed to investigate the prognosis and risk factors of capecitabine maintenance therapy and analysed the circulating tumour DNA (ctDNA) markers that may be related to the treatment response.MethodsThis study recruited 482 consecutive patients with MBC who achieved clinical benefit from capecitabine-based chemotherapy from 2011 to 2019. A total of 256 patients received subsequent capecitabine maintenance therapy. The baseline clinical factors included age at diagnosis, menopause, neoadjuvant therapy, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status and subtypes, prior treatment lines, and prior capecitabine-based treatment response. Treatment outcome (progression-free survival, PFS) was assessed by imaging tools according to RSCIST 1.1 standard during the first two treatment cycles and every 3 weeks thereafter. Univariate and multivariate Cox proportional hazards models were used to analysethe association between capecitabine maintenance treatment and prognosis.ResultsThe median PFS of patients receiving capecitabine maintenance treatment was 21.7 months [95% confidence interval (CI): 15.1–36.3 months]. Capecitabine maintenance showed similar effects as endocrine maintenance or anti-HER2 therapy in hormone receptor (HR)-positive or HER2-positive patients, with adjusted HR of 1.17 (95% CI: 0.81–1.71, P=0.40). In patients with triple-negative breast cancer (TNBC), capecitabine maintenance showed a marginal benefit in PFS. Compared to late-line (≥2) capecitabine maintenance, first-line capecitabine maintenance significantly prolonged median PFS. Compared to other HR/HER2 subtypes, patients with HR-positive and HER2-positive subtypes significantly benefited from capecitabine maintenance treatment. Analysis of ctDNA revealed that among patients receiving capecitabine maintenance, TP53 aberrations were concentrated in patients with short PFS.ConclusionsCapecitabine maintenance treatment is associated with longer PFS in patients with MBC, especially those receiving first-line capecitabine-based chemotherapy and those with HR positivity/HER2 positivity. TP53 aberrations may be responsible for the poor response to capecitabine maintenance treatment.

Impact of capecitabine maintenance on survival outcomes in triple-negative breast cancer patients not attaining pathological complete response following neoadjuvant chemotherapy: Real-world data from a tertiary care center from India.

e12593 Background: Capecitabine maintenance has demonstrated a survival benefit in triple-negative breast cancer (TNBC) patients not achieving pathological complete response (pCR) following neo-adjuvant chemotherapy (NACT). However, there is scarcity of data from Indian sub-continent corroborating the benefit of capecitabine maintenance. Methods: This retrospective study comprised of 161 TNBC patients registered at our institute between a period of May 2013 to Dec 2020, who received NACT (sequential anthracycline and taxane) but did not achieve pCR. Capecitabine was added to the institutional protocol since 2017 for maintenance therapy of TNBC patients who didn’t achieve pCR post NACT. Using Kaplan-Meir survival analysis and multivariate cox-proportional hazard models, we analysed differences in the relapse-free survival (RFS) and overall survival (OS) among those who received capecitabine maintenance therapy (n=80) versus those who did not receive it (n=81). Results: Distribution of age, family history, baseline performance score, tumor size, node positivity and clinical stage at time of presentation were comparable between the study groups, except for menopausal status (50% in control vs 33% in capecitabine group). Median(IQR) follow up time was 22.2 (16.2-27.4) months in capecitabine groups vs 19.3 (11.7-35.1) in control group. Twenty-three (28.8%) women in the capecitabine group had a disease-relapse while 45.7% (n=37) had relapsed in control group (p=0.026). Median RFS was 20.4 (17.8-25.9) months in control group while it was not reached in capecitabine group (log rank p=0.007). Adjusted for other baseline clinical characteristics, hazard of disease-relapse was significantly lower in the capecitabine group compared to controls [adjusted Hazard Ratio (aHR), 95% CI: 0.57 (0.34-0.96), p=0.035]. Median OS was not achieved in both the study groups, however, the hazard of death was lower in capecitabine group compared to control [aHR(95%CI): 0.44 (0.20-1.01), p-0.053]. Stratified by menopausal status, effect of capecitabine maintenance on disease relapse and RFS was only significant among the post-menopausal women [aHR (95%CI): 0.24 (0.10-0.59)]. Conclusions: This is the first study from our country, demonstrating a survival benefit with capecitabine maintenance in patients with TNBC not achieving pCR following NACT, particularly in post-menopausal women. It is an important observation as most of our patients present with locally advanced disease where pCR rate is low.

P-135 Capecitabine maintenance chemotherapy in the treatment of metastatic colorectal cancer: A meta-analysis

Many agents have been evaluated as maintenance therapy for metastatic colorectal cancer (mCRC), but there is no consensus on the optimal regimen. This study assessed the effect of single-agent capecitabine maintenance therapy on the survival outcomes of mCRC patients.

Capecitabine Maintenance Chemotherapy in the Treatment of Metastatic Colorectal Cancer: A Meta-Analysis

AbstractMany agents have been evaluated as maintenance therapy for metastatic colorectal cancer (mCRC), but there is no consensus on the optimal regimen. This study assessed the effect of single-agent capecitabine maintenance therapy on the survival outcomes of mCRC patients. A comprehensive literature search was performed according to prespecified inclusion and exclusion criteria for randomized controlled trials (RCTs) comparing capecitabine as maintenance monotherapy versus active monitoring for mCRC patients. Data on overall survival (OS), progression-free survival (PFS), time to tumor progression (TTP), adverse events, and quality of life (QoL) scores were extracted. Three RCTs with a total of 576 patients were included. Pooled analyses found neither OS benefit (HR:0.85, 95% CI:0.64–1.13) nor reduction in mortality at 24 months (RR:0.88, 95% CI:0.66–1.17) with capecitabine maintenance. Compared with active monitoring, capecitabine maintenance therapy improved PFS (HR:0.36, 95% CI:0.26–0.61) and reduced the risk of progression at 6 months (HR:0.78, 95% CI:0.56–1.10). The incidence of any grade ≥ 3 toxicity was higher with maintenance therapy than with observation (OR:2.02, 95% CI:1.42–2.88). No difference in terms of QoL was observed. Single-agent capecitabine as maintenance for patients with mCRC provides no OS benefit but results in statistically significant improvement in PFS with increased risk of toxicity. Hence, it may be considered particularly for patients who wish to delay the need for second-line treatment and who can tolerate it well.

Efficacy and safety analysis of bevacizumab combined with capecitabine in the maintenance treatment of RAS-mutant metastatic colorectal cancer.

What is known and objectivesThe optimal strategy for maintenance therapy in patients with metastatic colorectal cancer (mCRC) remains controversial. Considering that, beyond progression, co‐therapy with bevacizumab and cytotoxic chemotherapy showed less toxicity and a significant disease control rate. We aimed to investigate the differences in efficacy and safety between bevacizumab combined with capecitabine maintenance therapy and capecitabine monotherapy for RAS‐mutant mCRC （as defined by mutations in KRAS and NRAS exons 2–4）controlled by bevacizumab plus FOLFIRI chemotherapy for at least 12 weeks.MethodsWe retrospectively analysed patients with RAS‐mutant mCRC admitted to the Department of Oncology, Huizhou Municipal Central Hospital from December, 2015 to December, 2020. All patients were first treated with bevacizumab combined with FOLFIRI for at least 12 weeks of induction therapy. 154 patients whose disease was brought under control then continued maintenance therapy. 78 patients were in the observation group (bevacizumab plus capecitabine) and 76 patients were in the control group (capecitabine alone). The efficacy and adverse effects of maintenance treatment were compared between the two groups. The clinicopathological characteristics such as sex, age, performance status (PS) score, primary tumour site, degree of pathological differentiation, baseline carcinoembryonic antigen (CEA) level, microsatellite instability (MSI) status, number of metastatic tumour sites and efficacy of induction treatment were compared in terms of prognosis.Results and discussionThe median progression‐free survival (mPFS)of patients was 9.0 months (95% CI 8.0–10.0) in the observation group and 7.2 months (95% CI 6.0–8.4) in the control group, with a statistically significant difference (p < 0.05). The baseline CEA level was an independent prognostic factor. Both groups tolerated the toxic side effects.What is new and conclusionBevacizumab combined with capecitabine was well tolerated and contributed to a longer PFS time than capecitabine alone, and it is worthy of popularization in clinical practice.

Effect of Capecitabine Maintenance Therapy Plus Best Supportive Care vs Best Supportive Care Alone on Progression-Free Survival Among Patients With Newly Diagnosed Metastatic Nasopharyngeal Carcinoma Who Had Received Induction Chemotherapy

Capecitabine maintenance therapy improves survival outcomes in various cancer types, but data are limited on the efficacy and safety of capecitabine maintenance therapy in metastatic nasopharyngeal carcinoma (NPC). To investigate the efficacy and safety of capecitabine maintenance therapy in metastatic NPC. This randomized phase 3 clinical trial was conducted at Sun Yat-sen University Cancer Center from May 16, 2015, to January 9, 2020, among 104 patients with newly diagnosed metastatic NPC who had achieved disease control after 4 to 6 cycles of induction chemotherapy with paclitaxel, cisplatin, and capecitabine. The final follow-up date was May 30, 2021. All efficacy analyses were conducted in the intention-to-treat population. Eligible patients were randomly assigned (1:1) to receive either capecitabine maintenance therapy (1000 mg/m2 orally twice daily on days 1-14) every 3 weeks plus best supportive care (BSC) (capecitabine maintenance group) or BSC alone after 4 to 6 cycles of induction chemotherapy. Progression-free survival (PFS). Secondary end points were objective response rate, duration of response, overall survival, and safety. This study included 104 patients (84 men [80.8%]; median age, 47 years [IQR, 38-54 years]), with 52 assigned to the capecitabine maintenance group and 52 assigned to the BSC group. After a median follow-up of 33.8 months (IQR, 22.9-50.7 months), there were 23 events (44.2%) of progression or death in the capecitabine maintenance group and 37 events (71.2%) of progression or death in the BSC group. Median PFS survival was significantly higher in the capecitabine maintenance group (35.9 months [95% CI, 20.5 months-not reached]) than in the BSC group (8.2 months [95% CI, 6.4-10.0 months]), with a hazard ratio of 0.44 (95% CI, 0.26-0.74; P = .002). Higher objective response rates and longer median duration of response were observed in the capecitabine maintenance group (25.0%; 40.0 months) compared with the BSC group (objective response rate, 25.0% [n = 13] vs 11.5% [n = 6]; and median duration of response, 40.0 months [95% CI, not reached-not reached] vs 13.2 months [95% CI, 9.9-16.5 months]). The most common grade 3 or 4 adverse events during maintenance therapy were anemia (6 of 50 [12.0%]), hand-foot syndrome (5 of 50 [10.0%]), nausea and vomiting (3 of 50 [6.0%]), fatigue (2 of 50 [4.0%]), and mucositis (2 of 50 [4.0%]). No deaths in the maintenance group were deemed treatment-related. In this phase 3 randomized clinical trial, capecitabine maintenance therapy significantly improved PFS for patients with newly diagnosed metastatic NPC who achieved disease control after capecitabine-containing induction chemotherapy. Capecitabine exhibited manageable toxic effects. ClinicalTrials.gov Identifier: NCT02460419.

Clinical Complete Remission of An Advanced Gastric Adenocarcinoma After Camrelizumab Plus Chemotherapy Followed by Camrelizumab Plus Capecitabine: A Case Report

We report a rare case of PDL1-negative advanced gastric adenocarcinoma that improved significantly after camrelizumab plus chemotherapy followed by camrelizumab plus capecitabine as first-line therapy. A 65-year-old woman was diagnosed with a gastric adenocarcinoma in 2017 via contrast-enhanced computed tomography (CT) and endoscopic biopsy. She stabilised after preoperative neoadjuvant chemotherapy, surgery, and postoperative adjuvant chemotherapy. In September 2019, positron emission tomography (PET)/CT re-examination suggested a peritoneal metastasis and multiple lymph node metastases. She then received six cycles of camrelizumab plus chemotherapy. PET/CT indicated that the metastatic foci had disappeared and that she had achieved a clinical complete response(CCR). She was followed-up with camrelizumab plus capecitabine (maintenance therapy). At the time of writing, her progression-free survival is more than 14 months and her quality of life is good. Thus, camrelizumab plus chemotherapy is a useful first-line treatment for HER2- and PD-L1-negative advanced gastric adenocarcinoma.

Do all patients with locoregionally advanced nasopharyngeal carcinoma benefit from the maintenance chemotherapy using S-1/capecitabine?

BackgroundThe goal of this study was to explore the benefits of S-1/capecitabine as maintenance therapy in locoregionally advanced nasopharyngeal carcinoma (NPC) patients with different risks of treatment failure. MethodsA total of 2205 eligible, locoregionally advanced NPC patients were recruited for this retrospective study. Multivariate Cox regression analysis was performed to identify optimal predictors of overall survival (OS) and distant metastasis-free survival (DMFS) for constructing the nomograms. Patients were stratified into high-risk or low-risk groups based on the total score of the nomograms. Propensity score matching (PSM) was performed to match the maintenance and non-maintenance cohorts in different risk groups. A log-rank test was performed to evaluate correlations between maintenance therapy and survival. ResultsA nomogram for OS was established (C-index, 0.664; 95% confidence interval, 0.635–0.693). The 5-year OS rate was significantly higher in the low-risk group than in the high-risk group (83.5% vs. 67.2%, P < 0.001). Patients in the high-risk group who received S-1/capecitabine maintenance therapy achieved significant improvement in the 5-year OS rate (82.8% vs. 67.1%, p = 0.034), whereas patients in the low-risk group did not (86.7% vs. 80.9%, P = 0.081). There was no significant difference in OS, DMFS, progression-free survival (PFS), or toxicities between the S-1 and capecitabine groups (all P > 0.05), and overall treatment-related adverse events (AEs) were not severe (grade 1–2). ConclusionS-1/capecitabine maintenance therapy could prolong OS for locoregionally advanced NPC patients in the high-risk group. The toxicities of S-1/capecitabine maintenance therapy were mild and tolerable. Our findings can help guide maintenance therapy in locoregionally advanced NPC.

Capecitabine maintenance therapy after induction chemotherapy in newly diagnosed metastatic nasopharyngeal carcinoma: An open-label, randomized, controlled, phase trial.

6044 Background: Capecitabine maintenance therapy improves outcomes in various tumor types, but minimal data are available on the effect of capecitabine maintenance therapy in metastatic nasopharyngeal carcinoma (NPC). We aimed to investigate whether capecitabine maintenance therapy would prolong the progression-free survival (PFS) of newly diagnosed metastatic NPC, in comparison to best supportive care (BSC). Methods: This was an open-label, randomized, controlled, phase trial. Eligible patients for maintenance randomisation were aged 18-65 years old with newly diagnosed metastatic NPC at the Sun Yat-Sun University Cancer Center (SYSUCC), had completed 4 to 6 cycles of induction chemotherapy as per protocol and had achieved disease control to protocol treatment, including capecitabine. Patients were randomly assigned 1:1 to capecitabine maintenance (oral 1,250 mg/m2/day on days 1-14 every 21 days) for up to 24 months with BSC or BSC alone. The primary endpoint was PFS. The secondary endpoints included overall survival, duration of response, objective response rate and adverse effects. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02460419 and is ongoing and no longer recruiting new patients. Results: Between May 16th, 2015, and January 9th, 2020, 140 metastatic NPC patients were screened, and 104 eligible patients were randomly assigned to capecitabine maintenance plus BSC (n = 52) or BSC alone (n = 52). After a median follow-up of 33.1 months (IQR, 21.5-50.7 months), median PFS was 35.2 months in the capecitabine maintenance group and 9.1 months in the BSC group (HR: 0.426; 95%CI: 0.248-0.731, P = 0.001). The most commongrade 3 or 4 adverse events during maintenance therapy were hand-foot syndrome (10.0%), nausea/vomiting (6.0%), fatigue (4.0%), and mucositis (4.0%). Totally 37 deaths occurred during follow-up, 14 (26.9%) in the capecitabine maintenance group and 23 (44.2%) in the BSC group. Overall survival data was immature. No deaths in the capecitabine maintenance group were deemed treatment related. Conclusions: Capecitabine maintenance significantly improved PFS in patients with newly diagnosed metastatic NPC who achieved disease control after induction chemotherapy compared to BSC and exhibited low grade and manageable toxicities. Clinical trial information: NCT02460419.

The prognostic and predictive significance of cytokeratin 5/6 and epidermal growth factor receptor in metastatic triple-negative breast cancer treated with maintenance capecitabine.

BackgroundCapecitabine is the most widely used agent for maintenance chemotherapy in patients with metastatic triple-negative breast cancer (mTNBC). However, there are no biomarkers for identifying mTNBC patients who could benefit from capecitabine maintenance.MethodsThe prognostic roles of cytokeratin 5/6 (CK5/6), epidermal growth factor receptor (EGFR), and maintenance therapy were evaluated in mTNBC patients. Both CK5/6 and EGFR were detected using immunohistochemistry. Of 115 patients who achieved disease control, 56 received capecitabine maintenance therapy and 59 underwent observation. The progression-free survival (PFS) and overall survival (OS) of the patients were evaluated.ResultsThe median PFS and OS were longer in the maintenance group than that in the observation group (7.3 versus 5.7 months, P=0.0016; 22.4 versus 17.9 months, P=0.0055). Patients with basal-like TNBC had a poorer survival times than in those with non-basal-like TNBC (P=0.0062). Capecitabine maintenance significantly prolonged the OS of non-basal-like TNBC patients (P=0.0257), while in the basal-like TNBC patients, the difference was not significant (P=0.0541). Multivariate analysis revealed that the prolonged OS was related to age >50 years (P=0.005), presence of visceral metastases (P=0.035), response to initial therapy (P=0.017), maintenance therapy (P=0.033), and CK5/6 and EGFR status (P=0.032). Compared with the observation group, toxicities of all grades were more frequently observed in the maintenance group, including neutropenia, 85.71% vs. 25.87%, P<0.001; thrombocytopenia, 55.36% vs. 11.86%, P<0.001; anemia, 82.14% vs. 52.54%, P= 0.001; nausea 83.47% vs. 11.86%, P<0.001; vomiting 69.64% vs. 8.47%, P<0.001; and hand-foot syndrome (HFS) 32.14% vs. 1.69%, P<0.001.ConclusionsOur study revealed that patients with non-basal-like TNBC had a better clinical outcome than those with basal-like TNBC, and capecitabine maintenance treatment significantly prolonged PFS and OS in patients with TNBC. Patients with non-basal-like TNBC could benefit from maintenance therapy with capecitabine and CK5/6 and EGFR are biomarkers for TNBC prognosis.

Abstract PS13-01: Primary analysis of OVERSTEP: A multicenter, randomized clinical trial of capecitabine or endocrine therapy as a maintenance therapy after the 1st-line chemotherapy in hormone receptor positive and HER2-negative advanced/metastatic breast cancer

Abstract Background: Endocrine therapy(ET) and Chemotherapy(CT) are used as standard maintenance therapy for HR+ and HER2- metastatic breast cancer(MBC) in clinical practice. There was no prospective study data on which is better. In OVERSTEP, we provide some strong evidence for clinical practice. Methods: OVERSTEP(NCT02597868) is a multicenter, randomized, open-label, prospective clinical trial that enrolled 181 patients in China. patients aged 18-70 years without chemotherapy for ABC/MBC previously, histologically confirmed metastatic HR+ and HER2- breast cancer, and ECOG performance status of 0-1. These patients were received capecitabine plus another chemotherapy drug as 1st-line salvage chemotherapy at least 4 cycles. The patients response are CR, PR and SD carried maintenance treatment next, randomly assigned (1:1) to receive either capecitabine single or endocrine therapy. Randomization was done centrally with stratification by endocrine resistance and visceral metastasis. The primary endpoint was progression-free survival(PFS) and analyses were base on all patients who received at least one dose maintenance therapy. We take superiority test in the 2 groups. Results: 136(75.14%) patients were randomized after combined chemotherapy to capecitabine single or endocrine therapy groups for maintenance treatment. 45(24.86%) patients are progress disease (PD) after combined chemotherapy. After a median follow-up of 24.3 months (IQR 20.46-37.25 ) in the endocrine maintenance therapy group and 24.1 months(IQR 20.67-36.77) in the Capecitabine maintenance therapy group ,the hazard ratio for PFS was 0.625(95%CI 0.429-0.909 P=0.013),Median PFS was 17.5 months(95%CI 11.544-23.856) in endocrine maintenance therapy group and 12,2 months(95%CI 11.170-13.230) in capecitabine maintenance therapy group. In endocrine sensitive group, the hazard ratio for PFS was 0.515(95%CI0.269-0.988 P=0.042), Median PFS was 29.3 months(95%CI 14.605-43.995) in endocrine maintenance therapy group and 14.8 months(95%CI 7.445-22.155) in capecitabine maintenance therapy group. In endocrine resistance group, the hazard ratio for PFS was 0.791(95%CI 0.499-1.253 P=0.314), Median PFS was 13.6 months(95%CI 9.111-18.089) in endocrine maintenance therapy group and 12.0 months(95%CI10.357-13.643) in capecitabine maintenance therapy group. In visceral metastasis group, the hazard ratio for PFS was 0.668(95%CI0.410-1.089 P=0.101), Median PFS was 14.3 months(95%CI 11.113-17.487) in endocrine maintenance therapy group and 11.0 months(95%CI 8.140-13.860) in capecitabine maintenance therapy group. In non-visceral metastasis group, the hazard ratio for PFS was 0.54(95%CI0.300-0.972 P=0.037), Median PFS was 25.3 months(95%CI 15.278-35.322) in endocrine maintenance therapy group and 17.0months(95%CI 10.783-23.217) in capecitabine maintenance therapy group. Conclusions: For HR+ and HER2- MBC, after 1st-line salvage combined chemotherapy, ET maintenance has a better survival benefits than CT,especially for ET-sensitive and non-visceral involved cases. So ET maintenance is the first choice for ABC/MBC after 1st-line combined chemotherapy. Citation Format: Jian Huang, Xiying Shao, Li Cai, Yanxia Shi, Zhanhong Chen, Ping Huang, Yongmei Yin, Lili Zhang, Peng Shen, Wenming Cao, Weiwu Ye, Yuan Huang, Caijin Lou, Lei Lei, Yabin Zheng, Weibin Zou, Junqing Chen, Xiaojia Wang. Primary analysis of OVERSTEP: A multicenter, randomized clinical trial of capecitabine or endocrine therapy as a maintenance therapy after the 1st-line chemotherapy in hormone receptor positive and HER2-negative advanced/metastatic breast cancer [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 PS13-01.

Capecitabine in combination with bendamustine in pretreated women with HER2-negative metastatic breast cancer: results of a phase II trial (AGMT MBC-6).

Background:Bendamustine, a medication approved for the treatment of indolent non-Hodgkin lymphoma, has already shown anticancer activity in metastatic breast cancer (MBC). Here, we present the results of a phase II trial of bendamustine in combination with capecitabine in pre-treated patients with MBC.Patients and methods:AGMT MBC-6 is a multicentre, open-label, single-arm phase II study in HER2-negative MBC. All patients were pre-treated with anthracyclines and/or taxans and had measurable disease. Patients received per os 1000 mg/m2 capecitabine twice daily on days 1 to 14 in combination with 80 mg/m2 bendamustine intravenously on days 1 and 8 of a 3-week cycle for a maximum of eight cycles, followed by a capecitabine maintenance therapy. The primary endpoint was overall response rate (ORR).Results:From September 2013 to May 2015, 40 patients were recruited in eight Austrian centres. The median age was 60 years (range 29–77). Twenty-five per cent of patients had triple-negative breast cancer (TNBC) and 93% showed visceral involvement. With 17 partial and one complete remission, ORR was 46%. Median progression-free survival (PFS) was 7.5 months [95% confidence interval (CI) 6.1–10.7]. The most common non-haematological adverse events (AEs) of grade 3 were hand-foot syndrome (13%), fatigue (10%), nausea (8%), and dyspnoea (8%). One grade 4 non-haematological AE (hepatic failure) and three grade 4 haematological AEs (neutropenia) were observed. One patient died of restrictive cardiomyopathy, in which a relationship to capecitabine cannot be excluded, but seems unlikely.Conclusion:The combination of capecitabine and bendamustine shows promising efficacy and moderate toxicity. Further evaluation of this drug combination is warranted.The clinical trial AGMT MBC-6 was registered at ClinicalTrials.gov, (https://clinicaltrials.gov/; identifier: NCT01891227).

Effect of Capecitabine Maintenance Therapy Using Lower Dosage and Higher Frequency vs Observation on Disease-Free Survival Among Patients With Early-Stage Triple-Negative Breast Cancer Who Had Received Standard Treatment

Among all subtypes of breast cancer, triple-negative breast cancer has a relatively high relapse rate and poor outcome after standard treatment. Effective strategies to reduce the risk of relapse and death are needed. To evaluate the efficacy and adverse effects of low-dose capecitabine maintenance after standard adjuvant chemotherapy in early-stage triple-negative breast cancer. Randomized clinical trial conducted at 13 academic centers and clinical sites in China from April 2010 to December 2016 and final date of follow-up was April 30, 2020. Patients (n = 443) had early-stage triple-negative breast cancer and had completed standard adjuvant chemotherapy. Eligible patients were randomized 1:1 to receive capecitabine (n = 222) at a dose of 650 mg/m2 twice a day by mouth for 1 year without interruption or to observation (n = 221) after completion of standard adjuvant chemotherapy. The primary end point was disease-free survival. Secondary end points included distant disease-free survival, overall survival, locoregional recurrence-free survival, and adverse events. Among 443 women who were randomized, 434 were included in the full analysis set (mean [SD] age, 46 [9.9] years; T1/T2 stage, 93.1%; node-negative, 61.8%) (98.0% completed the trial). After a median follow-up of 61 months (interquartile range, 44-82), 94 events were observed, including 38 events (37 recurrences and 32 deaths) in the capecitabine group and 56 events (56 recurrences and 40 deaths) in the observation group. The estimated 5-year disease-free survival was 82.8% in the capecitabine group and 73.0% in the observation group (hazard ratio [HR] for risk of recurrence or death, 0.64 [95% CI, 0.42-0.95]; P = .03). In the capecitabine group vs the observation group, the estimated 5-year distant disease-free survival was 85.8% vs 75.8% (HR for risk of distant metastasis or death, 0.60 [95% CI, 0.38-0.92]; P = .02), the estimated 5-year overall survival was 85.5% vs 81.3% (HR for risk of death, 0.75 [95% CI, 0.47-1.19]; P = .22), and the estimated 5-year locoregional recurrence-free survival was 85.0% vs 80.8% (HR for risk of locoregional recurrence or death, 0.72 [95% CI, 0.46-1.13]; P = .15). The most common capecitabine-related adverse event was hand-foot syndrome (45.2%), with 7.7% of patients experiencing a grade 3 event. Among women with early-stage triple-negative breast cancer who received standard adjuvant treatment, low-dose capecitabine maintenance therapy for 1 year, compared with observation, resulted in significantly improved 5-year disease-free survival. ClinicalTrials.gov Identifier: NCT01112826.

Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line therapy in patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma.

TPS458 Background: First-line standard of care in patients with locally advanced or metastatic G/GEJ adenocarcinoma is fluoropyrimidine- and platinum (plat)-based combination chemotherapy. Despite improved chemotherapy regimens, outcomes remain poor and survival is low. Tislelizumab, an investigational humanized IgG4 monoclonal antibody with high affinity and binding specificity for PD-1, was engineered to minimize binding of FcγR on macrophages in order to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. Previous reports from early phase studies suggested tislelizumab, as a single agent and combined with chemotherapy, was generally well tolerated and had antitumor activity in patients with advanced solid tumors, including G/GEJ cancer. Methods: This randomized, placebo-controlled phase 3 study (NCT03777657) is designed to evaluate plat/fluoropyrimidine + tislelizumab vs plat/fluoropyrimidine + placebo as first-line therapy for patients with locally advanced or metastatic G/GEJ adenocarcinoma. Adult patients (n≈720) from ~160 centers will be randomized 1:1 to receive tislelizumab (200 mg IV Q3W) or placebo in combination with chemotherapy. Oxaliplatin (130 mg/m² IV Q3W) + capecitabine (1000 mg/m2 orally BID for 2 weeks) or cisplatin (80 mg/m² IV Q3W) + 5-fluorouracil (800 mg/m2/day IV on Days 1-5 Q3W) will be used as backbone chemotherapy on an individual basis. Chemotherapy will be administered for up to 6 cycles; capecitabine maintenance therapy is optional for patients who received capecitabine and oxaliplatin. Progression-free and overall survival are primary endpoints of the study. Secondary endpoints will include overall response rate, quality-of-life outcomes, and the safety/tolerability profile of combination therapy. Exploratory endpoints include disease control rate, time to response, and an analysis of potential predictive biomarkers including PD-L1 expression; the VENTANA PD-L1 (SP263) assay will be used for PD-L1 expression analysis. This study is actively enrolling. Clinical trial information: NCT03777657.

The role of capecitabine as maintenance therapy in de novo metastatic nasopharyngeal carcinoma: A propensity score matching study.

BackgroundCapecitabine was previously used as a second‐line or salvage therapy for metastatic nasopharyngeal carcinoma (NPC) and has shown satisfactory curative effect as maintenance therapy in other metastatic cancers. This study aimed to explore the role of capecitabine as maintenance therapy in de novo metastatic NPC patients with different plasma Epstein‐Barr virus (EBV) DNA levels before treatment.MethodsWe selected de novo metastatic NPC patients treated with locoregional radiotherapy (LRRT) for this retrospective study. The propensity score matching (PSM) was applied to balance potential confounders between patients who underwent capecitabine maintenance therapy and those who did not with a ratio of 1:3. Overall survival (OS) was the primary endpoint. The association between capecitabine maintenance therapy and survival was assessed using the log‐rank test and a Cox proportional hazard model.ResultsAmong all patients eligible for this study, 64 received capecitabine maintenance therapy after LRRT. After PSM, 192 patients were identified in the non‐maintenance group. In the matched cohort, patients treated with capecitabine achieved a higher 3‐year OS rate compared with patients in the non‐maintenance group (68.5% vs. 61.8%, P = 0.037). Multivariate analysis demonstrated that capecitabine maintenance therapy was an independent prognostic factor. In subgroup analysis, 3‐year OS rate was comparable between the maintenance and non‐maintenance groups in patients with high pretreatment EBV DNA levels (˃30,000 copies/mL) (54.8% vs. 45.8%, P = 0.835), whereas patients with low pretreatment EBV DNA levels (≤30,000 copies/mL) could benefit from capecitabine maintenance therapy in OS (90.0% vs. 68.1%, P = 0.003).ConclusionCapecitabine maintenance therapy may be superior to non‐maintenance therapy in prolonging OS for de novo metastatic NPC patients with pretreatment EBV DNA ≤ 30,000 copies/mL.

A phase III trial-in-progress comparing tislelizumab plus chemotherapy with placebo plus chemotherapy as first-line therapy in patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma.

TPS2655 Background: In patients (pts) with locally advanced or metastatic G/GEJ cancer, fluoropyrimidine- and platinum (plt)-based combination chemotherapy is first-line standard of care. Despite improvement in chemotherapy regimens, outcomes are poor and survival remains low. Tislelizumab, an investigational anti-PD-1 antibody, was engineered to minimize binding of FcγR on macrophages in order to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. Previous reports suggested tislelizumab, as a single agent and in combination with chemotherapy, was generally well tolerated and had antitumor activity in pts with advanced solid tumors, including G/GEJ cancer. Methods: This global, double-blind, randomized, phase 3 study (NCT03777657) is designed to compare plt/fluoropyrimidine + tislelizumab versus plt/fluoropyrimidine + placebo as first-line therapy for pts with locally advanced or metastatic G/GEJ cancer. Approximately 720 pts from 160 centers will be randomized 1:1 to receive tislelizumab (200 mg IV Q3W) or placebo (IV Q3W) in combination with chemotherapy. Oxaliplatin (130 mg/m² IV Q3W) plus capecitabine (1000 mg/m2 orally twice daily for 2 weeks) or cisplatin (80 mg/m² IV Q3W) plus 5-fluorouracil (800 mg/m2/day IV on Days 1–5 Q3W) will be used as backbone chemotherapy on an individual basis. Chemotherapy will be administered for up to 6 cycles; capecitabine maintenance therapy is optional for pts who received capecitabine and oxaliplatin. PD-L1 expression will be assessed using the VENTANA PD-L1 (SP263) assay. Progression-free survival and overall survival are primary endpoints in the intent-to-treat and PD-L1-positive analysis sets of the study. Secondary endpoints include overall response rate, duration of response, quality-of-life outcomes, and the safety/tolerability profile of combination therapy. Exploratory endpoints include disease control rate, time to response, and an analysis of potential predictive biomarkers including, but not limited to, PD-L1 expression. Clinical trial information: NCT03777657.

Curative effect of capecitabine maintenance therapy on the recurrence and metastasis of triple-negative breast cancer

Objective To study the maintenance treatment curative effect of capecitabine chemotherapy on recurrent triple-negative breast cancer patients. Methods From December 2012 to December 2014, 60 cases of recurrent triple-negative breast cancer were studied, and randomly divided into experimental group and control group (n=30 each). In the experimental group, the patients were treated with a combination chemotherapy regimen containing capecitabine during the rescue treatment and the curative efficacy was effective, and after complete of the combination chemotherapy capecitabine was ginve continuously to recurrence of the disease progression. In the control group, the chemotherapy was stopped after the rescue treatment was effective and the condition was stable. The effective rate, the time to the disease progression and the adverse reactions were statistically analyzed. Results The effective rate in the experimental group (50.0%) was significantly higher than in the control group (40.0%, P=0.039). The maintenance treatment time in the experiental group was 2.3-19.3 months (mean 6.6 months), and the median progression-free survival (PFS) was 10.6 months. In the control group, the time to the disease progression was 4.3 months. There was significant difference in the time to the disease progress between two groups (P=0.026). In the experimental group, the adverse reactions during maintenance treatment were bone marrow suppression (36.6%), liver and kidney dysfunction (40.0%), hand foot syndrome (46.7%), gastrointestinal reactions (60.0%). Conclusion Capecitabine as the maintenance treatment regimen for three-negative breast cancer can effectively improve the patient’s symptoms, and delay the progress of the disease. Key words: Capecitabine; Recurrence; Metastasis; Triple-negative breast cancer