First-line Chemotherapy Regimen Research Articles

Evaluation of the Treatment Duration of Japanese Patients With Pancreatic Cancer in a Real-World Setting Using a Large Hospital Claims Database: The SUISEI Study.

To clarify the treatment reality of pancreatic cancer in Japan, focusing on treatment duration and time to death. We retrospectively analyzed Japanese hospital claims data for patients diagnosed with pancreatic cancer between April 2009 and October 2018 to investigate treatment patterns, duration of first-line chemotherapy, and time to death. Of 81,185 eligible patients, 54.2% were male, the mean age was 71.7 years, and 23.3% (n = 18,884) received chemotherapy as primary treatment. The median treatment duration was 14.1 weeks for the 6.7% of patients who received oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX; recommended first-line regimen) and 16.9 weeks for the 30.2% of patients who received gemcitabine plus nab-paclitaxel (GEM + nab-PTX). Time to death for patients who received FOLFIRINOX or GEM + nab-PTX was similar (15.4 and 14.8 months, respectively). The duration of first-line chemotherapy regimens tended to increase annually for both regimens. The time to death for all first-line chemotherapy regimens also increased annually. This study revealed the treatment reality of pancreatic cancer in the real-world Japanese setting. Treatment duration and time to death tended to increase over time and did not differ numerically between FOLFIRINOX and GEM + nab-PTX.

J-AVENUE: A retrospective, real-world study evaluating patient characteristics and outcomes in patients with advanced urothelial carcinoma treated with avelumab first-line maintenance therapy in Japan.

The JAVELIN Bladder 100 phase 3 trial showed that avelumab first-line maintenance + best supportive care significantly prolonged overall survival and progression-free survival versus best supportive care alone in patients with advanced urothelial carcinoma who were progression-free following first-line platinum-based chemotherapy. We report findings from J-AVENUE (NCT05431777), a real-world study of avelumab first-line maintenance therapy in Japan. Medical charts of patients with advanced urothelial carcinoma without disease progression following first-line platinum-based chemotherapy, who received avelumab maintenance between February and November 2021, were reviewed. Patients were followed until June 2022. The primary endpoint was patient characteristics; secondary endpoints included time to treatment failure and progression-free survival. In 79 patients analyzed, median age was 72 years (range, 44-86). Primary tumor site was upper tract in 45.6% and bladder in 54.4%. The most common first-line chemotherapy regimen was cisplatin + gemcitabine (63.3%). Median number of chemotherapy cycles received was four. Best response to chemotherapy was complete response in 10.1%, partial response in 58.2%, and stable disease in 31.6%. Median treatment-free interval before avelumab was 4.9 weeks. With avelumab first-line maintenance therapy, the disease control rate was 58.2%, median time to treatment failure was 4.6 months (95% CI, 3.3-6.4), and median progression-free survival was 6.1 months (95% CI, 3.6-9.7). Findings from J-AVENUE show the effectiveness of avelumab first-line maintenance in patients with advanced urothelial carcinoma in Japan in clinical practice, with similar progression-free survival to JAVELIN Bladder 100 and previous real-world studies, supporting its use as a standard of care.

Abstract PO2-05-14: Prognosis and clinicopathological characteristics of HER2-negative metastatic breast cancers with low expression of hormone receptors: real world evidence from the French ESME cohort

Abstract Background: HER2-negative breast cancers expressing low (1-9 %) immunohistochemistry levels of hormone receptors (HR, estrogen and progesterone receptors), remain an uncertain category, being considered either as triple negative breast cancers (TNBC) or HR-positive (HR+) tumors across guidelines or approvals. The issues regarding this clinical subgroup are both prognostic, with the need of a better definition of their clinical outcome, as well as predictive. Methods: The ESME database is a French National cohort of all consecutive patients who initiated a first-line treatment for metastatic breast cancer (MBC) from 2008 on, in one of the 18 French Comprehensive Cancer Centers. Patients with HER2-negative (0 to 2+, ISH negative) MBC and known estrogen receptor (ER) and progesterone receptors (PR) expression levels were selected. Primary objective was to evaluate crude overall survival (OS) in HER2-/HR-low (ER and PR 0-9 and not TNBC) MBC pts compared with those with TNBC and HR+ disease defined by ER and PR < 1%, and ER ± PR ≥ 10%, respectively. In these 3 populations, predefined secondary objectives were to evaluate PFS under first line chemotherapy (CT), to describe clinical characteristics and the distribution of genetic abnormalities identified at the time of MBC diagnosis. Results: Out of 30,459 patients in the ESME database initiating their MBC treatment between 01/2008 and 01/2021, 19109 patients (2113 TNBC; 228 HR-low; 16768 HR+) were eligible for this analysis. Median follow-up was 58.0 months (95%CI [56.6; 59.0]). Median OS were 15.7 months [15.0-16.8], 19.1 months [15.5-22.4] and 44.6 months [43.8-45.5] in the TNBC, HR-low and HR+ subgroups, respectively. The multivariable analysis adjusted on age at MBC diagnosis, pathological grade and subtype, metastatic-free interval, number and sites of metastases and HER2 status (0 vs. 1-2+), identified no significant OS difference between HR-low and TNBC subgroups (HR=0.95, 95%CI 0.79-1.14), while HR+ patients had a better OS than TNBC patients (reference) (HR=0.50, 95%CI 0.47-0.53). Of these 19109 pts, 8910 received first-line CT regimen (1960 TNBC; 195 HR-low; 6755 HR+): taxanes-based: 66.7%, anthracyclines-based: 32.9%, capecitabine: 18%. Median PFS under first line CT were 5.3 (5.1-5.6), 5.1 (4.1-6.2) and 10.2 months (9.9-10.6) for TNBC, HR-low and HR+ subgroups, respectively. In the multivariable analysis adjusted on the same variables, the HR-low subgroup had a statistically poorer PFS compared to TNBC (HR=1.24, 95% CI 1.04-1.49). On the other hand, the HR+ subgroup had a better PFS than the TNBC (HR=0.74, 95%CI [0.70; 0.78]). Baseline germline BRCA1 mutations (at MBC diagnosis) were present in 4.5% of the TNBC cases, 2.6% of the HR-low cases, and 0.4% of the HR+ cases. The distribution of germline BRCA2 mutations was more homogeneous between the three groups (0.9% of TNBC cases, 1.3% of HR-low cases and 1.1 % of HR+ cases). Conclusions: In this large cohort, patients with HER2-negative, HR-low MBC seem to share similar general prognosis, oncogenetic features and PFS under standard chemotherapy treatment with TNBC patients. Citation Format: Marie Alexandre, Ludovic Gauthier, Audrey Mailliez, Thibault DE LA MOTTE ROUGE, Thomas Bachelot, Monica Arnedos, Florence Dalenc, Etienne Brain, Jean-Marc Ferrero, Vincent Massard, Isabelle Desmoulins, Marie-Ange Mouret-Reynier, Christelle Levy, Anthony Gonçalves, Marianne Leheurteur, Thierry Petit, Jean-Sébastien Frenel, Lise Bosquet, Suzette Delaloge, William Jacot. Prognosis and clinicopathological characteristics of HER2-negative metastatic breast cancers with low expression of hormone receptors: real world evidence from the French ESME cohort [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-05-14.

Study Design and Rationale for IFCT- 2203 TAXIO: A study that aims to evaluate the effectiveness of a first-line chemotherapy regimen without etoposide, combined with durvalumab, for patients with extensive disease Small Cell Lung Cancer.

BackgroundStudies have shown improvement in overall survival with anti-PD1/PD-L1 molecules in combination with cisplatin/carboplatin and etoposide as a first-line treatment for Small Cell Lung Cancer (SCLC). However, first-line efficacy remains limited and well below that observed in Non-Small Cell Lung Cancer (NSCLC). Etoposide may have a detrimental effect on lymphocyte activation, which could explain the limited benefit of immunotherapy in the first line and the lack of benefit in the second line for patients previously exposed to high levels of etoposide. MethodsWe initiated a multicenter, single-arm, open-label phase II study of a chemotherapy regimen with durvalumab, combined with carboplatin and paclitaxel for extensive disease SCLC. Eligible patients will receive durvalumab plus carboplatin and paclitaxel every 3 weeks for up to 4 cycles, followed by durvalumab every 4 weeks until progression or unacceptable toxicity. A total of 67 patients will be enrolled in this study, with a 12-month enrollment period and 36-month follow-up. The primary endpoint is Overall Survival (OS) rate at 12 months. Secondary endpoints are best response rate, OS, OS at 24- and 36 months, progression free survival (PFS), duration of response, quality of life and safety. ResultsThis study aims to establish the efficacy of durvalumab combined with carboplatin and paclitaxel in patients with extensive disease Small Cell Lung Cancer. Clinical trial registrationEU CT: 2023-504670-38-00.

Prognostic value of different radiation-related cell death genes in patients with lung adenocarcinoma

Background and aimsRadiotherapy is widely applied for lung adenocarcinoma (LUAD), while individualized differences led to different outcomes. This study aimed to establish a multi-gene risk scoring model to predict the benefits of LUAD patients from radiotherapy, based on different types of cell death respectively. ResultsOther than autophagy, pyroptosis, ferroptosis and Immunogenic cell death (ICD), the LUAD prognostic model based on apoptosis had the best performance, and the area under curves (AUCs) of the receiver operating curve (ROC) for 1-, 3-, and 5-year OS were 0.700,0.736,0.723,respectively. Such genes were involved as SLC7A5, EXO1, ABAT, NLRP1 and GAR1. Then patients were divided into high and low risk groups by the median apoptosis-LUAD risk score. For patients in the high-risk group, i.e., the radiotherapy-tolerant group, we screened adjuvant chemotherapy and found that besides the conventional first-line chemotherapy regimen, drugs such as Fludarabine, Pevonedistat, and Podophyllotoxin Bromide may also have potential therapeutic value. ConclusionThe multi-gene risk scoring model based on apoptosis might predict the radiotherapy benefits of LUAD patients and for those radioresistant patients classified by the model we also provided effective adjuvant chemicals, which would be used to guide clinical treatment.

Abstract 4553: DXC004A, a novel EGFR antibody-tubulysin analog conjugate demonstrated potential to broaden therapeutic opportunities for non-small cell lung cancer

Abstract EGFR is a member of the epidermal growth factor receptor (HER) family, and the over-expression of EGFR plays an important role in the growth and progression of various tumors, including non-small cell lung cancer. Monoclonal EGFR antibodies, such as cetuximab and panitumumab, have proven efficacy in various types of cancer. However, treatment with the anti-EGFR agents can be associated with toxicities of the skin, nails, hair, and eyes. Nimotuzumab (Nimo) is the first humanized monoclonal antibody targeting EGFR and has been granted approval for use in squamous cell carcinoma of head and neck (SCCHN), glioma and nasopharyngeal cancer in different countries. In contrast to cetuximab, Nimotuzumab is distinguished by achieving higher or similar complete remission rate (CRR) or overall remission rate (ORR) of the primary tumor in clinical applications but much less toxicity, resulting in a better safety profile, which has been attributed to its about 10-fold lower affinity. Paclitaxel combined with cisplatin is the first-line chemotherapy regimen for non-small cell lung cancer. A phase 2 clinical trial has confirmed that Nimotuzumab combined with concurrent chemoradiation therapy (radiation concurrent with docetaxel and cisplatin, CCRT) was well tolerated for locally advanced squamous cell lung cancer. However, the combination strategy of Nimo-CCRT has only demonstrated similar OS and PFS to those in the CCRT group. DXC004A is an ADC drug targeting EGFR, in which a Nimotuzumab derivative and a Tubulysin B analog is conjugated by a functional linker. DXC004A is in phase I clinical trial and has demonstrated clinical activity in advanced non-small cell lung cancers and good tolerability. In vitro and in vivo results had confirmed that DXC004A monotherapy had better anti-tumor activity than the combination of Nimotuzumab and Tubulysin analog in HCC827 cell lines with high EGFR expression. Meanwhile, a single injection of low-dose DXC004 (2.5 mg/kg) in HCC827 xenograft model showed very good durable anti-tumor effect. Moreover, the combination of DXC004A with Cisplatin exhibited significantly better activities than that of Nimo-CCRT combination, DXC004A or cisplatin alone, in vitro and in vivo, which might solve the predicament of poor efficacy of Nimo-CCRT combination therapy. This synergy results suggested that DXC004A plus cisplatin would possibly be a new adjuvant therapy for non-small cell lung cancer in further clinical studies. Citation Format: Xiaobo Cai, Min Cao, Huihui Guo, Qingliang Yang, Yongxiang Chen, Xiangfei Kong, Yong Du, Zhicang Ye, Zhixiang Guo, Lingli Zhang, Lu Bai, Junxiang Jia, Yunxia Zheng, Wei Zheng, Jun Zheng, Wenjun Li, Yuanyuan Huang, Zhongliang Fan, Binbin Chen, Meng Dai, Robert Y. Zhao. DXC004A, a novel EGFR antibody-tubulysin analog conjugate demonstrated potential to broaden therapeutic opportunities for non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4553.

Comparison of efficacy and safety of 5-FU or capecitabine combined with cisplatin and docetaxel (mDCF and mDCX) as a first-line chemotherapy regimen in her 2-negative metastatic gastric cancer patients: A retrospective study.

The prognosis of metastatic gastric cancer (GC) is poor, with a median survival time of less than a year. Capecitabine is a prodrug, metabolized by thymidine phosphorylase to its cytotoxic metabolite (5-FU). Few studies have compared capecitabine and 5-FU in mGC. In this retrospective study, we compared the efficacy and safety of modified DCF (mDCF) (docetaxel, cisplatin, and 5-FU) and modified DCX (mDCX) (docetaxel, cisplatin, and capecitabine) regimens for first-line treatment in patients with mGC. The study included 112 mGC patients treated with either mDCF (n = 69) or mDCX (n = 43) between 2010 and 2021. Demographic data, response rate, progression-free survival (PFS), overall survival (OS), and adverse events were evaluated. The complete response rate in the mDCF group was 10.1%, whereas the complete response rate in the mDCX group was 2.3%. The partial response rate for mDCF and mDCX were 29% and 37%, respectively. The 2 treatment arms of the study had the same objective rate of response and disease control rate (DCR). PFS and OS rates were comparable between the 2 groups. The median PFS in the mDCF and mDCX arms were 6.0 months (95% CI, 4.87-7.14) and 5.0 months (95% CI, 4.10-5.90) respectively (P = .08). The median OS in the mDCF and mDCX arms were 9.0 months (95% CI, 7.53-10.47) and 9.0 months (95% CI, 6.87-11.11) respectively (P = .07). Neutropenia, asthenia, stomatitis, and nausea/vomiting were the most frequently reported grade 3 to 4 adverse events (AEs). The rates of grade 3/4 AEs and dose reduction were comparable between the 2 groups. There was no treatment discontinuation due to grade 3 to 4 AE. As a first-line treatment for patients with mGC, mDCX and mDCF regimens have comparable efficacy and tolerability profiles.

Efficacy of adding levofloxacin to gemcitabine and nanoparticle-albumin-binding paclitaxel combination therapy in patients with advanced pancreatic cancer: study protocol for a multicenter, randomized phase 2 trial (T-CORE2201)

BackgroundAdvanced pancreatic cancer is one of the leading causes of cancer-related deaths. For patients with advanced pancreatic cancer, gemcitabine and nanoparticle albumin-binding paclitaxel (nabPTX) combination (GEM/nabPTX) therapy is one of the recommended first-line treatments. Several retrospective studies have suggested that the addition of levofloxacin improves the efficacy of GEM/nabPTX therapy in patients with advanced pancreatic cancer. This prospective study aims to evaluate whether the addition of antibiotics improves the treatment efficacy of GEM/nabPTX as a first-line chemotherapy in patients with advanced pancreatic cancer.MethodsThis multicenter, prospective, randomized, phase 2 trial will included 140 patients. Patients with advanced pancreatic cancer will be randomized in a 1:1 ratio to either the GEM/nabPTX therapy group or the GEM/nabPTX plus levofloxacin group. The primary endpoint for the two groups is median progression-free survival time (mPFS) for the full analysis set (FAS). The secondary endpoints for the two groups are median overall survival (mOS), response rate (RR), disease control rate (DCR), and adverse event (AE) for the FAS and mPFS, mOS, RR, DCR, and AE for the per-protocol set. This study will enroll patients treated with GEM/nabPTX as the first-line chemotherapy for stage IV pancreatic adenocarcinoma.DiscussionGEM/nabPTX is a standard first-line chemotherapy regimen for patients with advanced pancreatic cancer. Recently, the superiority of 5-fluorouracil, liposomal irinotecan, and oxaliplatin combination therapy (NALIRIFOX) to GEM/nabPTX as first-line therapy for pancreatic cancer has been reported. However, the efficacy of NALIRIFOX is inadequate. Based on previous retrospective studies, it is hypothesized that treatment efficacy will improve when levofloxacin is added to GEM/nabPTX therapy. If the AEs (such as leukopenia, neutropenia, and peripheral neuropathy) that occur at an increased rate with levofloxacin and GEM/nabPTX combination therapy can be carefully monitored and properly managed, this simple intervention can be expected to improve the prognosis of patients with advanced pancreatic cancer.Trial registrationThis study was registered with the Japan Registry of Clinical Trials (jRCT; registry number: jRCTs021230005).

Tumour response following preoperative chemotherapy is affected by body mass index in patients with colorectal liver metastases.

Colorectal cancer is the third most prevalent malignancy globally and ranks second in cancer-related mortality, with the liver being the primary organ of metastasis. Preoperative chemotherapy is widely recommended for initially or potentially resectable colorectal liver metastases (CRLMs). Tumour pathological response serves as the most important and intuitive indicator for assessing the efficacy of chemotherapy. However, the postoperative pathological results reveal that a considerable number of patients exhibit a poor response to preoperative chemotherapy. Body mass index (BMI) is one of the factors affecting the tumorigenesis and progression of colorectal cancer as well as prognosis after various antitumour therapies. Several studies have indicated that overweight and obese patients with metastatic colorectal cancer experience worse prognoses than those with normal weight, particularly when receiving first-line chemotherapy regimens in combination with bevacizumab. To explore the predictive value of BMI regarding the pathologic response following preoperative chemotherapy for CRLMs. A retrospective analysis was performed in 126 consecutive patients with CRLM who underwent hepatectomy following preoperative chemotherapy at four different hospitals from October 2019 to July 2023. Univariate and multivariate logistic regression models were applied to analyse potential predictors of tumour pathological response. The Kaplan-Meier method with log rank test was used to compare progression-free survival (PFS) between patients with high and low BMI. BMI < 24.0 kg/m2 was defined as low BMI, and tumour regression grade 1-2 was defined as complete tumour response. Low BMI was observed in 74 (58.7%) patients and complete tumour response was found in 27 (21.4%) patients. The rate of complete tumour response was significantly higher in patients with low BMI (29.7% vs 9.6%, P = 0.007). Multivariate analysis revealed that low BMI [odds ratio (OR) = 4.56, 95% confidence interval (CI): 1.42-14.63, P = 0.011], targeted therapy with bevacizumab (OR = 3.02, 95%CI: 1.10-8.33, P = 0.033), preoperative carcinoembryonic antigen level < 10 ng/mL (OR = 3.84, 95%CI: 1.19-12.44, P = 0.025) and severe sinusoidal dilatation (OR = 0.17, 95%CI: 0.03-0.90, P = 0.037) were independent predictive factors for complete tumour response. The low BMI group exhibited a significantly longer median PFS than the high BMI group (10.7 mo vs 4.7 mo, P = 0.011). In CRLM patients receiving preoperative chemotherapy, a low BMI may be associated with better tumour response and longer PFS.

Effect of lung metastasis on the treatment and prognosis of patients with gestational trophoblastic neoplasia: A systematic review and meta-analysis.

Gestational trophoblastic neoplasia (GTN) is a highly invasive tumor, mainly spreading to the lungs. However, lung metastasis in GTN is usually not considered as an adverse prognostic factor. Therefore, the aim of this study was to summarize the results of previous studies and evaluate the effects of lung metastasis on the treatment and prognosis of GTN. The study was prospectively registered in PROSPERO (CRD42023372371). Electronic databases including PubMed, Embase, the Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang, and China Biomedical Literature Database were used for a systematical search of relevant studies published up to November 21, 2022. The observational studies reporting the clinical outcomes of GTN patients with and without lung metastasis were selected. The incidences of resistance, relapse, and mortality of GTN patients were extracted and successively grouped based on the presence of lung metastasis. The pooled relative risks (RRs) and 95% confidence interval (95% CI) of the eligible studies were calculated. The qualities of included studies were assessed with the Newcastle-Ottawa Scale and the certainty of evidence was graded based on the GRADE. The meta-analysis was performed using Stata 12.0 and GradePro software. Five publications with 3629 GTN patients were included. The meta-analysis revealed that the GTN with lung metastasis was strongly correlated with first-line chemoresistance (pooled RR = 1.40, 95% CI: 1.22 to 1.61, p < 0.001), recurrence (pooled RR = 3.03, 95% CI: 1.21 to 7.62, p = 0.018), and disease-specific death (pooled RR = 22.11, 95% CI: 3.37 to 145.08, p = 0.001). Ethnicity was also an important factor and Caucasian GTN patients with lung metastasis showed a higher risk of recurrence as revealed by the subgroup analysis (pooled RR = 5.10, 95% CI: 2.38 to 10.94, p < 0.001). GTN patients with lung metastasis exhibited a higher risk of chemoresistance, relapse, and disease-specific death. Patients with lung metastasis among the Caucasian population had a higher risk of recurrence than Asian populations. Therefore, the presence of lung metastases might be considered as a high-risk factor for prognosis of GTN and deserves more attention in the choice of first-line chemotherapy regimens and follow-up.

First-line monodrug chemotherapy in low-risk gestational trophoblastic neoplasia: a network meta-analysis.

The efficacy of the first-line monodrug chemotherapy has been generally established for low-risk GTN. Most patients can achieve a complete response after the first-line monodrug chemotherapy. However, which monodrug chemotherapy regimen is better for individual patients with GTN is not yet certain. This study aimed to assess the efficacy of first-line monodrug chemotherapy in low-risk gestational trophoblastic neoplasia (GTN). Databases, including PubMed, Embase, Web of Science, and Cochrane Library, were searched from inception to November 1, 2022, for case-control studies on first-line monodrug chemotherapy in GTN. Network meta-analysis was performed to compare the efficacy outcome of six monodrug chemotherapy regimens in GTN, with a complete response rate as the endpoint. Twenty-four studies were considered eligible, including 9 randomized controlled trials (RCTs) and 15 non-RCTs. A total of 3344 patients with low-risk GTN were involved. Six monodrug chemotherapy regimens were included and analyzed. In descending order of efficacy, these six regimens were VP-16 (5 days), ACT-D (5 days), MTX (5 days), ACT-D (1.25 mg/m2), MTX (8 days), and MTX (30-50 mg/m2) in all study, and five regimens were ACT-D (5 days), MTX (5 days), ACT-D (1.25 mg/m2), MTX (8 days), and MTX (30-50 mg/m2) in RCT. Among the six first-line monodrug chemotherapy regimens for low-risk GTN in all study, VP-16 (5 days) was the best in terms of efficacy. And five regimens in RCT, ACT-D was the best. However, the finding needs to be validated through more high-quality clinical studies.

Patient Profile and Survival Rate of Breast Cancer Patients with FEC Chemotherapy Regimen at H. Adam Malik Hospital

Breast cancer is a prevalent disease that impacts public health worldwide, including Indonesia. There are various chemotherapy regimens that are currently available. One widely utilized chemotherapy regimen for breast cancer is the FEC regimen, which combines 5-fluorouracil, epirubicin, and cyclophosphamide. This study provides a study of patient profiles and survival rates among breast cancer patients undergoing FEC chemotherapy at H. Adam Malik Hospital. The study utilized a descriptive-retrospective approach with data collected from the medical records of patients who underwent FEC therapy at RSUP H. Adam Malik during January-December 2019. A total of 157 patients were administered anthracycline-based treatment, with 54 patients receiving FEC (34.39%). The majority of individuals under the FEC regimen were primarily luminal B (51.75%) and IBC (33.33%). The survival rate for individuals using the FEC chemotherapy regimen was found to be 37.98 months. Additionally, patients with risk factors associated with invasive breast cancer (IBC) exhibited a 1.20-fold increased risk of mortality compared to individuals with other forms of breast cancer. The first-line FEC chemotherapy regimen continues to be a feasible therapeutic option for subtypes of breast cancer, and there is no discernible variation in survival rate observed across these characteristics.

Updated Results of a Prospective Study: Rituximab and Lenalidomide Plus Chidamide (RLC) for Patients with Relapsed/Refractory Angioimmunoblastic T-Cell Lymphoma

Introduction Angioimmunoblastic T-cell lymphoma (AITL) is the second most common subtype of peripheral T-cell lymphoma (PTCL). The therapeutic effect of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), the most common first-line chemotherapy regimen, is not satisfactory, and most patients experience relapse or disease progression. The 5-year progression-free survival (PFS) of AITL is 13%-23%, and 5-year overall survival (OS) is 33%-36%. The benzamide histone deacetylase inhibitor (HDACi) Chidamide and lenalidomide (a second-generation immunomodulatory compound) are both approved for the treatment of relapsed or refractory PTCL in China. About 70%-100% of the AITL patients have EBV infection, which may cause abnormal immune functions in hosts. EBV infects immunocytes such as B cells, T cells, and natural killer cells, and it impairs immune functions that can clear neoplastic cells from the body. Rituximab may eradicate EBV-B cells and activated B cells and may prevent the progression to AITL. When combined with rituximab, lenalidomide augmented antibody-dependent cell-mediated cytotoxicity by enhancing NK cells, which overcomes rituximab resistance in lymphoma patients. In this prospective phase II study, the efficacy and safety of a new regimen consisting of rituximab, lenalidomide and chidamide has been evaluated in relapsed/refractory AITL patients. We have reported the preliminary results (2022 ASH, poster 1600), and now we update the data of this study. Methods Patients with relapsed/refractory AITL after at least first-line chemotherapy were treated with up to 6 cycles of a rituximab and lenalidomide plus chidamide (RLC) regimen every 3 weeks. The initial dose of each drug has been reported. The primary endpoint of the study was PFS. The secondary endpoints included overall response rate (ORR), OS, and adverse events (AEs). Results Between Aug 2019 and May 2023, 24 patients with relapsed/refractory AITL were enrolled. The characteristics of these patients are listed in table 1. On enrollment, 16 (66.7%) patients had received 1st-line chemotherapy, 7 (29.1%) patients had received 2nd-line chemotherapy, and 1 (4.2%) patient had received 3rd-line chemotherapy. The median age was 63 years (range 43-78) and 9 (37.5%) patients were female. Fifteen (62.5%) patients had B symptoms, including weight loss in 3 (12.5%) cases, night sweat in 1 (4.2%) case and fever in 11 (45.8%) cases. Sixteen (66.7%) patients had elevated serum lactate dehydrogenase (LDH), and 21 (87.5%) patients had IPI score≥2. All patients had completed RLC treatment for at least 1 cycle and underwent imaging assessment. The ORR was 75% (18/24) with a complete remission (CR) rate of 20.8% (5/24), and 13 (54.2%) patients achieved partial remission (PR). While 1 (4.2%) patient achieved stable disease (SD) and 5 (20.8%) patients achieved progressive disease (PD). Two patients received autologous hematopoietic stem cell transplantation as consolidation treatment after achieving CR from RLC chemotherapy. With a median follow-up of 9.7 months, 9 patients had died. The median PFS was 10.8 months (95% confidence interval &amp;lt;CI&amp;gt;, 9.0 to 12.6 months), but the median OS was not reached. No patient presented with Grade 5 AE. The most frequent all-grade hematological toxicity included leucopenia (35.7%, 5/14), followed by anemia (21.4%, 3/14) and thrombocytopenia (41.7%, 10/24). Other common toxicities included infusion reaction (16.7%, 4/24), skin rash (20.8%, 5/24), pulmonary pneumonia (41.7%, 10/24), and nausea (12.5%, 3/24). Dose reduction was performed in 8 patients. The exploratory analysis of possible prognostic factors by mass spectrum flow are undergoing. Conclusions The updated results of this prospective study confirmed the good response rate and manageable toxicity of rituximab and lenalidomide plus chidamide (RLC) regimen. This combination may be a promising regimen in patients with relapsed/refractory AITL.

Clinical efficacy of Camrelizumab combined with first-line chemotherapy in extensive-stage small-cell lung cancer

ObjectiveExploring the clinical efficacy of camrelizumab in combination with first-line chemotherapy in patients with extensive-stage small-cell lung cancer (ES-SCLC). MethodsThe clinical data of 35 patients with ES-SCLC who received camrelizumab combined with EC or EP regimen in First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from January 2020 to January 2023 were retrospectively analyzed. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were OS, ORR and DCR. SPSS 25.0 software was used for statistical analysis, Kaplan-Meier curve and Log-Rank test analysis, and survival curve was drawn. ResultsThe median PFS of 35 patients with SCLC was 7.4 months (95 % CI 6.75–9.81 months), .and the median OS was 12.5 months (95% CI,11.71-16.90 months). The ORR and DCR were 65.7 % and 74.3 %, respectively. Adverse events (AEs) were mainly concentrated in grade 1–2, and the probability of occurrence of grade 3 or above was low. Reactive Cutaneous Capillary Endothelial Proliferation (RCCEP) was the most common, followed by nausea &vomit and anemia. The other common AEs included abnormal thyroid function, decreased neutrophil count, skin rash and leucopenia. ConclusionCamrelizumab in combination with first-line chemotherapy regimens prolonged OS and PFS in SCLC patients and showed efficacy and safety in real-world data.

Real-world treatment outcomes of metastatic biliary tract cancer patients in Japan: the Tokushukai REAl-world data project 04 (TREAD 04).

To investigate temporal trends in treatment patterns and prognostic factors for overall survival in patients with metastatic biliary tract cancer. From the Tokushukai REAl-world Data project, we identified 945 patients with metastatic biliary tract cancer treated with gemcitabine, tegafur/gimeracil/oteracil, gemcitabine plus cisplatin, gemcitabine plus tegafur/gimeracil/oteracil or gemcitabine plus cisplatin and tegafur/gimeracil/oteracil between April 2010 and March 2022. Stratified/conventional Cox regression analyses were conducted to examine the association between overall survival and patient- and tumour-related factors, study period, hospital volume, hospital type and first-line chemotherapy regimen. Using inverse probability of treatment weighting with propensity scores, overall survival was also compared between monotherapy and combination therapy groups. We enrolled 366 patients (199 men; median age, 72years). Over a median follow-up of 5.2months, the median overall survival was 7.0months (95% confidence interval 6.2-9.0), and the median time to treatment failure was 3.5months (95% confidence interval 3.1-4.5). Median overall survival and time to treatment failure for gemcitabine/tegafur-gimeracil-oteracil/gemcitabine plus cisplatin/gemcitabine plus tegafur-gimeracil-oteracil/gemcitabine plus cisplatin and tegafur-gimeracil-oteracil regimen were 6.2/6.6/7.9/16.2/15.1 and 2.8/3.4/4.1/15.3/7.4months, respectively. Primary disease site, previous surgery, previous endoscopic procedures and hospital type were identified as significant prognostic factors. Inverse probability of treatment weighting analysis demonstrated that combination therapy had a significantly better prognosis than monotherapy (hazard ratio 0.61, 95% confidence interval 0.43-0.88, P=0.006). Our real-world data analysis showed that standard care for metastatic biliary tract cancer is widely used in hospitals throughout Japan and verified the survival benefits of combination therapy over monotherapy observed in prior clinical trials. UMIN000050590 (http://www.umin.ac.jp/ctr/index.htm).

1679P Comparison of first-line chemotherapy regimens in unresectable locally advanced or metastatic pancreatic cancer: A systematic review and network meta-analysis

1679P Comparison of first-line chemotherapy regimens in unresectable locally advanced or metastatic pancreatic cancer: A systematic review and network meta-analysis

Poor Survival Outcomes in Patients with Stage IIIC2 Cervical Cancer Receiving Concurrent Chemoradiotherapy

Patients with cervical cancer who have para-aortic lymph nodes metastasis are staged as IIIC2 according to the 2018 FIGO staging system. In this study, we evaluated the survival and toxicity outcomes of patients with stage IIIC2 cervical cancer who received concurrent chemoradiotherapy. We included patients with stage IIIC2 cervical cancer who received definitive concurrent chemoradiotherapy at our institute between 2007 and 2015. The treatment consisted of intensity modulated radiation therapy (IMRT) delivering a dose of 50.4 Gy in 28 fractions to the pelvic and para-aortic lymph node regions, with escalated doses of 60-70 Gy for positive lymph nodes. A dose of 30 Gy in 5 fractions was delivered with intracavitary brachytherapy. The first-line chemotherapy regimen was weekly cisplatin. A total of 88 patients were included in the study. The median follow-up periods for all patients and surviving patients were 20 months (range: 5-114 months) and 62 months (range: 5-114 months), respectively. The median survival was 20.9 months. The 1-year, 3-year, 5-year, and 8-year overall survival rates were 73.4%, 41.3%, 34.5%, and 25.3%, respectively, while the progression-free survival rates were 50.8%, 29.7%, 28.4%, and 21.2%. The local control rates were 58.6%, 52.2%, 52.2%, and 42.8%, respectively. Multivariate analysis showed that the number of positive para-aortic lymph nodes and histology type were independent factors affecting progression-free survival. The 5-year progression-free survival rates were 40.2% and 0% for patients with one and two or more positive para-aortic lymph nodes, respectively, and 30.1% and 21.4% for patients with squamous cell carcinoma and adenocarcinoma, respectively. Grade 3 or higher toxicities were observed in 8 patients (9.1%), including 4 patients (4.5%) with gastrointestinal toxicities and 4 patients (4.5%) with genitourinary toxicities. The results of this study suggest that the survival outcomes of patients with stage IIIC2 cervical cancer receiving concurrent chemoradiotherapy were poor. Further treatment options, such as consolidation chemotherapy or immunotherapy, should be considered for these patients.

Effect of Cinobufacini plus platinum-based chemotherapy regimen on the immune function of patients with non-small-cell lung cancer: A meta-analysis

BackgroundCinobufacini is a Chinese medicinal preparation extracted from the traditional Chinese medicine toad skin and is commonly used clinically as an adjuvant treatment for malignant tumours. PurposeTo systematically evaluate the effects of Cinobufacini combined with a first-line platinum-based chemotherapy regimen in patients with non-small-cell lung cancer (NSCLC), especially in terms of immune function. Materials and methodsEight electronic databases were searched for randomised controlled trials (RCTs) investigating Cinobufacini in conjunction with platinum-based chemotherapy for NSCLC (stage III-IV) published from 2012 to the present. GRADE Pro GDT was used to assess RCT quality and meta-analysis was performed mainly using Review Manager version 5.4, with the assistance of Stata version 16.0 (StataCorp LLC, College Station, TX, USA), and trial sequential analysis software. ResultsA total of 35 studies were included. Meta-analysis revealed that the combination therapy group exhibited a better disease control rate (DCR) [OR = 2.63, 95%CI (2.15, 3.21), P < 0.00001], with a higher one-year [OR = 2.41,95% CI (1.75,3.33), P < 0.00001], and two-year [OR = 2.28, 95% CI (1.56,3.33), P < 0.00001] survival rate, plus lower leukocyte toxicity [OR = 0.40, 95%CI (0.33,0.49), P < 0.00001]. For immune function, the combination of chemotherapy with Cinobufacini effectively increased the proportion of CD3+ [SMD = 1.15, 95% CI (0.89,1.42), P < 0.00001], CD4+ [SMD = 1.60, 95%CI (1.26,1.94), P < 0.00001] and the CD4+/CD8+ ratio [SMD = 2.15, 95% CI (1.45,2.86), P < 0.00001] in peripheral blood. ConclusionThe addition of Cinobufacini to platinum-based chemotherapies for advanced NSCLC significantly improved clinical efficacy, enhanced immune function, and reduced chemotherapeutic toxicity, irrespective of administration and treatment duration.

Nursing Alchemy: Transforming R-CHOP Information Into Essentials.

A combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is a first-line combination chemotherapy regimen for diffuse large B-cell lymphoma that has many nursing implications. Understand.

Hepatic arterial infusion chemotherapy plus lenvatinib with or without programmed cell death protein-1 inhibitors for advanced cholangiocarcinoma.

New treatment strategies are needed to improve outcomes for patients with advanced cholangiocarcinoma (CCA) due to the limited efficacy of current first-line chemotherapy regimens. Although the combination of hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and programmed cell death protein-1 (PD-1) inhibitors has been extensively evaluated in the treatment of advanced hepatocellular carcinoma, their roles in advanced CCA remain poorly understood. The purpose of this study is to compare the efficacy and safety of HAIC plus lenvatinib with or without PD-1 inhibitors in patients with advanced CCA. Between March 2019 to June 2022, patients diagnosed with advanced CAA who received HAIC plus lenvatinib with or without PD-1 inhibitors treatment were reviewed for eligibility. Efficacy was evaluated according to survival and tumor response, and safety was evaluated according to the incidence of adverse events (AEs). Fifty-five patients with advanced CCA were included in the study, and they were divided into the HAIC+lenvatinib (LEN)+PD-1 inhibitors (PD-1i) group (n = 35) and HAIC+LEN group (n = 20). The median follow-up time was 14.0 (5-42) months. Patients in the HAIC+LEN+PD-1i group had significantly better PFS (HR = 0.390; 95% CI 0.189-0.806; p = 0.001) and OS (HR = 0.461; 95% CI 0.229-0.927; p = 0.01) than those in the HAIC+LEN group. The HAIC+LEN+PD-1i group showed a higher objective response rate and disease control rate than the HAIC+LEN group but did not find a significant difference. The incidence of grade 1-2 and grade 3-4 AEs was not significantly higher in the HAIC+LEN+PD-1i group compared to the HAIC+LEN group, whereas two patients (5.7%) in the HAIC+LEN+PD-1i group experienced grade 5 immune-mediated pneumonia. HAIC plus lenvatinib with PD-1 inhibitors is safe and well-tolerated, and has the potential to prolong the survival of patients with advanced CCA. The addition of PD-1 inhibitors may enhance the efficacy of HAIC and lenvatinib. Therefore, the combined therapy has the potential to become a treatment option for advanced CCA.