First-line Chemotherapy In Patients Research Articles

Higher objective responses by hepatic arterial infusion chemotherapy following atezolizumab and bevacizumab failure than when used as initial therapy in hepatocellular carcinoma: a retrospective study.

Atezolizumab/bevacizumab (atezo-bev) is the first-line chemotherapy for patients with unresectable hepatocellular carcinoma (HCC). However, hepatic artery infusion chemotherapy (HAIC) can be used as an alternative. Our aim was to compare the prognosis of HAIC treatment between newly diagnosed patients and patients treated after failure of atezo-bev. We retrospectively assessed 73 patients with HCC treated with HAIC between January 2022 and September 2023. Fifty-seven patients were treated with HAIC at initial diagnosis, while 16 were treated with HAIC after first-line atezo-bev combination chemotherapy. We evaluated tumor responses, such as overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). No significant difference was observed in either OS or PFS between patients with HCC treated with HAIC at the initial diagnosis and those treated after atezo-bev treatment failure. However, the ORR of the initial HAIC group was 19.6% and that of the HAIC group after atezo-bev therapy failure was 43.6%, which was a statistically significantly difference. Although no significant difference was observed for OS and PFS, the ORR of patients in the HAIC group after the failure of atezo-bev therapy was superior to that of newly diagnosed patients. HAIC may prolong survival in patients with HCC after atezo-bev treatment failure.

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).

Effect of cancer cachexia on first-line chemotherapy in patients with advanced pancreatic cancer: a claims database study in Japan

BackgroundCancer cachexia is a multifactorial syndrome leading to progressive functional impairment. How cachexia affects the treatment course of chemotherapy in patients with pancreatic cancer has not been well understood.MethodsThis is an exploratory, retrospective, observational cohort study using the Japanese medical claims database from Medical Data Vision Co., Ltd. The study population included patients diagnosed with pancreatic cancer in whom first-line FOLFIRINOX (FFX) or gemcitabine plus nab-paclitaxel (GnP) was initiated between October 1, 2018, and September 30, 2020. In this study, we defined patients with cancer cachexia as those who had a weight loss of ≥ 5% in the preceding 6 months. The primary outcome was time-to-treatment failure (TTF). The observation period was six months from the initiation of first-line FFX or GnP treatment.ResultsA total of 1897 patients (421 patients into the cachexia group; 1476 patients into the non-cachexia group) were analyzed in this study. The median TTF was 121 days (95% confidence interval [CI] 94–146) in the cachexia group and 143 days (95% CI 134–152) in the non-cachexia group. The hazard ratio for TTF of the cachexia versus non-cachexia group was 1.136 (95% CI 0.979–1.319). The median number of doses was two doses fewer in the cachexia group than in the non-cachexia group for both FFX and GnP.ConclusionCancer cachexia was suggested to be associated with shorter TTF and a reduced number of doses in patients with pancreatic cancer who received first-line FFX or GnP treatment.Clinical Trial Registration clinicaltrials.jp: UMIN000045820.

Single-agent metronomic versus weekly oral vinorelbine as first-line chemotherapy in patients with HR-positive/HER2-negative advanced breast cancer: The randomized Tempo Breast study

IntroductionSingle-agent oral vinorelbine is a standard of care for hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) that has progressed on endocrine therapy. Metronomic administration may offer a better balance of efficacy and safety than standard regimens, but data from previous trials are scarce. MethodsIn this open-label, multicenter, phase II trial, patients were randomized to oral vinorelbine administered on a metronomic (50 mg three times weekly) or weekly (60 mg/m2 in cycle 1, increasing to 80 mg/m2 if well tolerated) schedule. Treatment was continued until disease progression or intolerance. The primary endpoint was disease control rate (DCR, the proportion of patients with a best overall confirmed response of CR, PR, or stable disease lasting 6 months or more). ResultsOne-hundred sixty-three patients were randomized and treated. The DCR was 63.4% (95% confidence interval [CI]: 52.0–73.8) with metronomic vinorelbine and 72.8% (95% CI: 61.8–82.1) with weekly vinorelbine. Weekly vinorelbine was also associated with longer progression-free survival (5.6 vs 4.0 months) and overall survival (26.7 vs 22.3 months) than metronomic vinorelbine, but was associated with more adverse events. ConclusionsIn this randomized phase II trial, single-agent metronomic oral vinorelbine was effective and well tolerated as first-line chemotherapy for patients with HR-positive/HER2-negative ABC. Formal comparisons are not done in this phase II study and one can simply observe that confidence intervals of all endpoints overlap. When deciding for a chemotherapy after failure of endocrine therapy and CDK 4/6 inhibitors, oral vinorelbine might be an option to be given with either schedule. Clinical trial registration numberEudraCT 2014-003860-19.

BAP1, Wilms’ tumor 1, and calretinin in predicting survival and response to first-line chemotherapy in patients with pleural mesothelioma

PurposeThere are currently no methods to predict response to chemotherapy in pleural mesothelioma (PM). The aim of this study is to investigate the predictive and prognostic role of BAP1, WT1 and calretinin expression and their combinations in pre-treatment tumor samples by immunohistochemical (IHC) staining.MethodsThe study included consecutive PM patients treated with chemotherapy alone at a University hospital between 2009 and 2020. BAP1 analyses were performed on formalin-fixed, paraffin-embedded tumor tissue samples of the patients, while WT1 and calretinin information were obtained from the histopathological diagnosis records.ResultsOf the total 107 patients included, 64% had loss of BAP1 expression, whereas 77% had WT1 and 86% had calretinin expression. Patients with the presence of BAP1 expression, one or both of the other two markers, or loss of expression of all three markers (unfavorable status) were more likely to not respond to chemotherapy than those with the presence of all three markers or loss of BAP1 expression and expression of one or two other markers (favorable status) (p = 0.001). Median survival time of patients with favorable and unfavorable status was 15 ± 1.7 and 8.0 ± 2.4 months, respectively (p = 0.027). After adjustment for histopathology and stage, loss of BAP1 (HR = 0.54, 95%CI 0.35–0.83), WT1 (1.75, 1.06–2.90), calretinin (2.09, 1.14–3.84) expression and favourable panel (0.50, 0.27–0.92) was associated with prognosis.ConclusionsThe IHC biomarkers BAP1, WT1, and calretinin, used in the routine diagnosis of PM and their combinations, are the first biomarkers associated with response to chemotherapy and may be a useful tool to select patients for first-line platinum pemetrexed treatment in PM patients. Validation in a large cohort is ongoing.

Prognostic factors for overall survival in patients with advanced digestive neuroendocrine carcinoma treated with first-line cisplatin-based chemotherapy: A post-hoc analysis of JCOG1213.

594 Background: Advanced digestive neuroendocrine carcinoma (ADNEC) is a rare and aggressive malignancy without evidence of prognostic factors assessed in prospective studies. We aimed to evaluate prognostic factors in patients with ADNEC receiving first-line cisplatin-based chemotherapy. Methods: This is a post-hoc analysis of JCOG1213, which is a phase 3 randomized trial showing equivalent overall survival (OS) for cisplatin plus etoposide versus cisplatin plus irinotecan as first-line chemotherapy for patients with ADNEC. The primary endpoint of JCOG1213 was OS. For this post-hoc analysis of prognostic factors, patients who had ineligible histology based on the central pathological review or who lacked the necessary clinical data for analysis were excluded. A Cox proportional hazard model was used to assess the effect of independent variables on OS. Priori variables selected on previous reports (performance status (PS), Ki-67 index, and serum LDH level), as well as variables that remained at a level of p-value <0.20 by backward stepwise selection, were incorporated in the final model of OS. Results: Among 170 patients enrolled in JCOG1213, a total of 129 patients with ADNEC were included in this analysis. In multivariable analysis, serum LDH level (> upper normal limit vs. normal) was identified as a significant prognostic factor for OS (HR = 1.721, 95% CI: 1.144–2.589, p = 0.009). Other clinicopathological factors were not found to be significant, including PS (1 vs. 0; HR = 0.784, 95% CI: 0.507–1.214, p = 0.276), Ki-67 (≥ 55% vs. < 55%; HR = 1.475, 95% CI: 0.588–3.698, p = 0.407), liver metastasis (present vs. absent; HR = 1.434, 95% CI: 0.968–2.124, p = 0.072), sex (female vs. male; HR = 1.387, 95% CI: 0.937–2.053, p = 0.102), and serum ALP level (> upper normal limit vs. normal; HR = 0.948, 95% CI: 0.639–1.406, p = 0.789). OS of patients with elevated serum LDH levels was shorter than those with normal serum LDH levels (median: 9.5 months vs. 15.6 months, p = 0.0019). No statistically significant differences were observed between the two groups regarding objective response rate (58.8% vs. 54.1%, p = 0.594) and progression-free survival (median: 4.5 months vs. 5.9 months, p = 0.141). A numerically lower proportion of patients with elevated serum LDH levels received second-line chemotherapy than those with normal serum LDH levels (76.5% vs. 88.3%). Conclusions: Serum LDH level may serve as a prognostic factor in the daily practice of patients with ADNEC and as a risk stratification factor in future randomized clinical trials. Clinical trial information: UMIN000014795 .

Impact of adding nivolumab to first-line chemotherapy in patients with advanced gastric cancer.

334 Background: Nivolumab plus chemotherapy (Nivo-Chemo) is the standard treatment for advanced gastric cancer based on the results of CheckMate 649 trial and ATTRACTION-4 trial. However, real-world data on the efficacy of Nivo-Chemo are limited. This study aimed to assess the efficacy of Nivo-Chemo in the clinical practice setting by comparing it to chemotherapy alone. Methods: We retrospectively reviewed the medical records of patients with advanced gastric cancer who received palliative chemotherapy in our hospital between 2017 and 2023. The inclusion criteria were as follows: age ≥ 20 years; histologically confirmed advanced unresectable or recurrent gastric/gastro-esophageal junction adenocarcinoma; HER2 negative or unknown; and no prior treatment. Patients were divided into two groups based on their first-line treatment: the Nivo-Chemo group and chemotherapy alone (Chemo) group. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR) were assessed. Results: Of 78 patients, 52 patients were in the Chemo group and 26 patients were in the Nivo-Chemo group. Median age were 69 years (range 30–83) and 67 years (range 39–76) in the Chemo group and Nivo-Chemo group. Eastern Cooperative Oncology Group performance status (ECOG PS) was 0/1/2 in 18/27/7 patients (35%/52%/13%) in the Chemo group and in 17/8/1 patients (65%/31%/4%) in the Nivo-Chemo group. Histological type (Intestinal type/diffuse type) was 19/33 (37%/63%) in the Chemo group and 8/18 (31%/69%) in the Nivo-Chemo group. Combined positive score (CPS) was assessed in 21 patients in the Nivo-Chemo group. The CPS <1/1-5/>5 was in 3/10/8 (12%/38%/31%). In the Chemo group, 28 patients (54%) received anti-PD-1 monotherapy after progression of first-line chemotherapy. The median PFS was 5.7 months in the Chemo group and 6.0 months in the Nivo-Chemo group (HR 0.88, 95% CI 0.50-1.55, p = 0.66). The median OS was 15.0 months in the Chemo group and 18.6 months in the Nivo-Chemo group (HR 0.76, 95% CI 0.37-1.53, p = 0.44). The ORR was 50% in the Chemo group and 54% in the Nivo-Chemo group, while the DCR was 63% and 69%, respectively. Conclusions: In clinical practice, the addition of nivolumab to chemotherapy tended to provide a survival benefit compared to chemotherapy alone.

A phase 2, open-label, safety and efficacy study of telotristat ethyl plus first-line chemotherapy in patients with advanced biliary tract cancer.

472 Background: Patients (pts) with unresectable biliary tract cancer (BTC) have a poor prognosis. In preclinical models of cholangiocarcinoma (CCA) telotristat ethyl (TE), a tryptophan hydroxylase inhibitor that reduces production of serotonin, enhanced the antiproliferative effects of gemcitabine and cisplatin (GC) chemotherapy. This trial assessed the safety and efficacy of adding TE to GC chemotherapy in pts with advanced BTC. Methods: This was a Phase 2 open-label study. Eligible pts had unresectable, locally advanced, or metastatic BTC, were treatment naïve and had plans to initiate GC chemotherapy. On Day 1, pts received Gem 1000mg/m2 and Cis 25mg/m2 with TE 250 mg orally three times daily (TID) for 7 days. Thereafter, pts received TE 500 mg TID continuously plus GC therapy on days 1 and 8 of each 21-day cycle. The study comprised of 2 stages: stage 1 would enroll 20 patients with a safety run-in cohort in the first 6 pts to monitor safety and tolerability of TE + GC treatment for 21 days. Stage 2 would enroll 33 patients if no significant/unresolved grade 3 or higher toxicities related to study drug occurred in stage 1. The primary endpoint was 6-month (mo) progression free survival (PFS) rate according to RECIST 1.1. If 60% of pts (≥34) in the safety population were alive and progression free at 6-mos, the study was considered successful. Secondary endpoints included overall response rate (ORR) and disease control rate (DCR). Restaging occurred every 9 weeks using RECIST 1.1 and toxicities were graded using CTCAE v 5.0. Results: Between 2019 and 2021, fifty-three pts were enrolled across 12 study sites and comprised the safety population. The majority of pts were female (62.3%) and median age was 66 yrs (range 33 to 79). Baseline mean plasma 5-HIAA was 11.1 µg/L (ULN defined as >10.8 µg/L). Thirty-one pts (58.5%) had plasma 5-HIAA levels ≤ULN and 22/53 (41.5%) had 5-HIAA levels >ULN. Majority of pts had metastatic BTC (85%) and liver was the most common primary tumor site (66%). The 6-month PFS rate was 22.6% (12/53). Based on blinded independent central review, the ORR was 13.2% and DCR was 62.3%. Mean reduction in plasma 5-HIAA at 6 mos was -1.735 µg/L (SD 8.69) in 24 patients with available data. There was no difference in 6-mo PFS rate based on pts baseline 5-HIAA status; 58% (14/24) pts had ≥30% decrease from baseline in 5-HIAA, however there was no correlation with 6-month PFS. The most common TE related TEAEs were constipation (43.4%), nausea (28.3%) and fatigue (28.3%). Conclusions: The study did not achieve its primary endpoint of 60% of patients on TE plus GC chemotherapy being alive and progression free at 6 months. TE did reduce 5-HIAA levels in a subset of pts; however, this did not correlate to improved clinical outcomes. No significant safety issues noted with TE in combination with GC chemotherapy. Clinical trial information: NCT03790111 .

Targeting Methionine Addiction Combined With Low-dose Irinotecan Arrested Colon Cancer in Contrast to High-dose Irinotecan Alone, Which Was Ineffective, in a Nude-mouse Model.

Colorectal cancer (CRC) is the third-leading cause of death in the world. Although the prognosis has improved due to improvement of chemotherapy, metastatic CRC is still a recalcitrant disease, with a 5-year survival of only 13%. Irinotecan (IRN) is used as first-line chemotherapy for patients with unresectable CRC. However, there are severe side effects, such as neutropenia and diarrhea, which are dose-limiting. We have previously shown that methionine restriction (MR), effected by recombinant methioninase (rMETase), lowered the effective dose of IRN of colon-cancer cells in vitro. The aim of the present study was to evaluate the efficacy of the combination of low-dose IRN and MR on colon-cancer in nude mice. HCT-116 colon-cancer cells were cultured and subcutaneously injected into the flank of nude mice. After the tumor size reached approximately 100 mm3, 18 mice were randomized into three groups; Group 1: untreated control on a normal diet; Group 2: high-dose IRN on a normal diet (2 mg/kg, i.p.); Group 3: low-dose IRN (1 mg/kg i.p.) on MR effected by a methionine-depleted diet. There was no significant difference between the control mice and the mice treated with high-dose IRN, without MR. However, low-dose IRN combined with MR was significantly more effective than the control and arrested colon-cancer growth (p=0.03). Body weight loss was reversible in the mice treated by low-dose IRN combined with MR. The combination of low-dose IRN and MR acted synergistically in arresting HCT-116 colon-cancer grown in nude mice. The present study indicates the MR has the potential to reduce the effective dose of IRN in the clinic.

Dissecting the genetic variations associated with response to first-line chemotherapy in patients with small cell lung cancer: a retrospective cohort study.

Chemotherapy has been the standard treatment for small-cell lung cancer (SCLC) for decades. Nonetheless, patients are usually responsive to initial chemotherapy but quickly suffer from relapse, resulting in a poor long-term outcome. Treating advances that greatly ameliorate survival outcomes are historically finite, and credible biomarkers for therapeutic evaluation are deficient. As the genetic biology emerges, investigating biomarkers to optimize individualized treatment for SCLC is necessary. Based on following inclusion criteria: (I) patients diagnosed as SCLC by pathology; (II) patients treated with first-line etoposide/cisplatin (EP) chemotherapy; (III) patients who received long-term follow-up and signed informed consent, a total of 24 SCLC patients receiving first-line standard chemotherapy were divided into progressive disease (PD) and partial response (PR) groups. They were regularly followed every 3 months with computed tomography (CT) scan until recurrences determined by CT scan results. Next-generation sequencing (NGS) with a panel of 1,406 cancer-related genes was conducted on the tumor tissue-derived DNA of patients to compare genetic variations, including deletions (indels), single nucleotide variations (SNVs), copy number variations (CNVs), and copy number instability (CNI) between the two groups. For the clinical characteristics of enrolled SCLC patients, except for significant differences in sex, age, clinical stage, and limited or extensive stage, PD patients showed distinctly shorter overall survival than those with PR (6.5 vs. 14.0 months, respectively, P=0.007). Genetic variations analysis discovered several common genes with CNV mutations between the PR and PD groups, and increased epidermal growth factor receptor (EGFR) gene copy numbers gain was found in PR groups in comparing with PD patients (P=0.006). However, no significant differences in terms of SNVs, indels, genotypes associated with first-line chemotherapy, CNI of tumor tissue-derived DNA, and tumor mutational burden of tumor tissues were observed between two groups. Additionally, the relationship between EGFR gene mutation and clinicopathological features of SCLC indicated that EGFR gene mutation may be an independent indicator for SCLC patients. Increased EGFR gene CNVs may be an independent indicator influencing the survival time and PR in SCLC patients receiving standard first-line chemotherapy.

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.

Efficacy of second-line chemotherapy after treatment with gemcitabine plus nab-paclitaxel or FOLFIRINOX in patients with metastatic pancreatic cancer

First-line chemotherapy for patients with metastatic pancreatic cancer (MPC) includes gemcitabine plus nab-paclitaxel (GnP) and FOLFIRINOX (FFX). However, the efficacy of second-line chemotherapy and the role of combination chemotherapy in clinical practice is still unknown. Data was gathered from 14 hospitals in the Kyushu area of Japan from December 2013 to March 2017. The median overall survival (mOS) from second-line treatment was contrasted between patients who received second-line chemotherapy (CT group) and those who received the best supportive care (BSC group). Furthermore, the mOS of combination chemotherapy was compared to mono chemotherapy in the CT group. To control possible bias in the selection of treatment, we performed a propensity score-adjusted analysis. A total of 255 patients received GnP or FFX as first-line chemotherapy. There were 156 in the CT group and 77 in the BSC group of these. The CT group had a significantly longer mOS than the BSC group (5.2 vs. 2.6 months; adjusted hazard ratio (HR) 0.38; 95% CI 0.27–0.54). In the CT group, 89 patients received combination chemotherapy while 67 received mono chemotherapy. The mOS did not differ significantly between the combination and mono chemotherapy groups (5.5 vs. 4.8 months; adjusted HR 0.88; 95% CI 0.58–1.33). Among patients with MPC receiving second-line treatment, the CT group had a significantly longer mOS than the BSC group, but combination chemotherapy conferred no improvement in survival compared to mono chemotherapy.

Trend in overall survival from the start of first-line chemotherapy in patients with metastatic urothelial carcinoma.

New approaches involving immune checkpoint inhibitors and antibody-drug conjugates prolong overall survival in patients with metastatic urothelial carcinoma. However, the access to such systemic therapy in clinical practice is suboptimal, and whether these agents improve overall survival in patients with metastatic urothelial carcinoma over time remains unclear. Hence, we investigated the overall survival trend from the initiation of first-line therapy with these agents to identify changes due to the medication and time of treatment initiation. We retrospectively evaluated 195 patients from a single center. They were treated with chemotherapy, pembrolizumab, or avelumab or enfortumab vedotin. The treatment was categorized into chemotherapy, pembrolizumab or avelumab/enfortumab vedotin period. The new agents prolonged overall survival from the start of first-line therapy. Furthermore, sequential treatment with these agents in real-world clinical practice has been reported to prolong overall survival. These study results will have major implications when a new first-line therapy is approved in the future.

Serum basic fibroblast growth factor and interleukin-1β predict the effect of first-line chemotherapy in patients with advanced gastric cancer.

The incidence and mortality rates of gastric cancer in China are the second-highest in the world, and most patients with gastric cancer lose their chance of surgery by the time of their diagnosis. To explore the predictive potential of serum basic fibroblast growth factor and interleukin-1β levels for the effect of first-line chemotherapy in patients with advanced gastric cancer. From the gastric cancer patients admitted to our hospital from May 2019 to April 2023, 84 patients were selected and randomly and equally assigned to the experimental or control group. The FLOT group received the FLOT chemotherapy regimen (composed of oxaliplatin + calcium folinate + fluorouracil + paclitaxel), while the SOX group received the SOX chemotherapy regimen (composed of oxaliplatin + tiga capsules). The clinical efficacy, tumor marker levels, adverse reactions, and survival rates of the two groups were compared 7 days after the end of the relevant treatments. The target effective rate of the FLOT group was 54.76%, which was much higher than that of the SOX group (33.33%; P < 0.05). After treatment, both the groups demonstrated lower levels of cancer antigen (CEA), carbohydrate antigen 199 (CA199), and peptide tissue antigen (TPS). For several patients before treatment (P < 0.05). Third and fourth grades. In terms of adverse reactions, the level of white blood cells in both the groups was lower. Moreover, the incidence of hand-foot skin reactions in these two study groups was lower (P < 0.05), while those of peripheral neuritis, vomiting, diarrhea, and abnormal liver function were significant (P < 0.05). No statistically significant difference was noted between the two groups (P < 0.05). The 1-year survival rate was higher in the FLOT group (P < 0.05). The FLOT regimen was effective in reducing the serum CEA, CA199, and TPS levels as well as in improving the 1-year survival rate of patients with good tolerability, making it worthy of clinical promotion and application.

Meta-analysis of studies on the effectiveness of adding anti-PD1 antibodies to the first-line chemotherapy in advanced esophageal cancer

Introduction: The results of six randomized control trials have been published by 2022, which evaluated the efficacy of adding PD-1 inhibitors to the first-line chemotherapy in patients with metastatic esophageal cancer. However, it still remains unclear which patients derive the most clinical benefit from combined therapy. Therefore, it is necessary to evaluate the efficacy of the combination of anti-PD1 treatment with chemotherapy in different patient subgroups.Materials and methods: We conducted a meta-analysis of randomized controlled trials in patients with stage IV esophageal cancer who received anti-PD1 drugs with different chemotherapeutic regimens in the first-line setting to select patients who benefit the most from the combined therapy.Results: Six randomized trials were included in the analysis for a total of 3,813 patients. Patients who received combination therapy had significantly longer OS (HR = 0.69, 95% CI: 0.63-0.75; p &lt; 0.001), PFS (HR = 0.62, 95% CI: 0.56-0.69; p &lt; 0.001), and better ORR (OR = 2.12, 95% CI: 1.85-2.42; p &lt; 0.001) than those who received chemotherapy alone. Subgroup analyses showed no benefit of adding PD1-inhibitors to chemotherapy in patients with PD-L1 CPS &lt;1 in terms of OS (HR = 0.58, 95 % CI: 0.31-1.1; p = 0.1) as well as in never-smokers (HR = 0.9, 95% CI: 0.67-1.23; p = 0.52).Conclusions: The addition of PD-1 inhibitors to the first-line chemotherapy in patients with metastatic esophageal cancer significantly improves treatment outcomes. Our results could not strongly suggest the selected patients' cohort which would benefit the most from the combination of PD-1 inhibitors and chemotherapy use.

Chemotherapy efficacy in metastatic neuroendocrine colorectal cancer

AIM: to evaluate the effectiveness of first-line chemotherapy in patients with colorectal neuroendocrine cancer (NEC).PATIENTS AND METHODS: a retrospective study included patients with metastatic colorectal NEC (2000-2020). The main analyzed parameter was the response rate to treatment according to the RECIST criteria, depending on the regimen used in the first line. The overall survival was additional parameter.RESULTS: the study included 27 patients (13 with initial stage IV disease and 14 with progression after primary radical treatment). Ten patients in the 1st line underwent chemotherapy according to the EP scheme, 4 — XELOX, 2 — FOLFIRI, 2 — Irinotecan and Cisplatin, 1 — Samarium, 1 — Nivolumab, 1 — 5-FU-LV. Most often, the treatment effect (partial response or stabilization) was observed against the background of chemotherapy according to the EP scheme — in 60% of patients. The median OS was 7 months.CONCLUSION: the use of chemotherapy according to the EP regimen is the preferred options for the treatment of metastatic colorectal NEC. The median OS in this group of patients remains extremely low, and new clinical trials are needed.

Exploring the significance of PARP inhibitor therapy after first-line chemotherapy in patients with homologous recombination proficient ovarian cancer: An extracted individual patient data and trial-level meta-analysis.

5580 Background: The use of poly (ADP-ribose) polymerase inhibitors (PARPi) as maintenance therapy in advanced epithelial ovarian cancer (EOC) patients (pts) has shown to delay cancer progression among patients with mutated BRCA (mBRCA) or homologous recombination deficiency (HRD), with debatable and divergent benefit among the subgroup of patients with homologous recombination proficiency (HRP). We aimed to further clarify the efficacy of PARPi after first-line chemotherapy (1L CT) in patients with HRP EOC. Methods: A systematic literature search of PubMed, Embase, The Cochrane Library until February 9th was conducted to identify articles or presentations of phase III clinical trials (P3CT) evaluating PARPi maintenance therapy after 1L CT in ovarian cancer. Individual patient data was reconstructed from Kaplan-Meier plots of progression-free survival (PFS) among pts with mBRCA, HRD and HRP through WebPlotDigitizer and R package IPDfromKM and futher combined. We also performed trial-level meta-analysis with a random effects model. Comparisons were made with Cox proportional hazards. Clinical benefit for each sub-group was accessed with the ESMO Magnitude of Clinical Benefit Formulary 2b (ESMO MBCS). Results: The literature search resulted in 513 items. After screening, 6 P3CT (SOLO1, PRIMA, VELIA, PAOLA, PRIME, and ATHENA-MONO) were selected, and the longer follow-up data of each trial was used. A total of 3205 pts were included in the analysis (2090 in PARPi arms, 1115 in control arms). HRP was associated with worse PFS regardless of the treatment arm (HRP vs mBRCA in PARPi arms: HR 1.92, 95% CI 1.62 – 2.21, P &lt; 0.001). Compared to control treatment arm, PARPi therapy was associated with a improved PFS in all subgroups, although the magnitude of benefit decreased from mBRCA to HRD and HRP (Table). Trial-level meta-analysis yielded similar results. PARPi therapy summed 4 out of 4 possible points at ESMO MBCS for mBRCA and HRD, but only 2 points among HRP pts, confirming a lower clinical benefit in this subgroup. Conclusions: This meta-analysis included additional P3CT recently presented and new data of subgroup analysis of previous studies. Results confirm a statistically significant benefit of PARPi maintenance after 1L CT for HRP EOC. Nevertheless, the relative and absolute gain in PFS is modest (9% in 2 years), while mBRCA and HRD subgroups have a substantial benefit. The worse prognosis of HRP pts, in addition to the small clinical benefit of PARPi therapy, highlights the need for new treatment strategies for this subgroup. [Table: see text]

GNRI Sustainability during One Cycle of First-Line Chemotherapy as a Prognostic Indicator in Patients with Metastatic Urothelial Carcinoma

Introduction: This study evaluated the prognostic value of a sustained high Geriatric Nutritional Risk Index (GNRI) during first-line chemotherapy for patients with metastatic urothelial carcinoma (mUC). Methods: Between January 2018 and February 2022, 123 patients received platinum-based chemotherapy at Nagoya City University Hospital and affiliated institutions. Of these, 118 eligible patients who showed an Eastern Cooperative Oncology Group performance status (ECOG-PS) between 0 and 2 were retrospectively examined. Based on body mass index and serum albumin levels, GNRI was calculated immediately before and after the first primary chemotherapy cycle. Patients were divided into two groups based on GNRI: GNRI sustained ≥92 in sustainable (n = 63) and GNRI <92 in unsustainable (n = 55) groups, respectively. Clinical outcomes were compared. Results: No significant differences were noted between the two groups for age, gender, cycle of first-line treatment, and type of series of sequential treatments after failure of first-line therapy. Median overall survival from the start of first-line chemotherapy was 30.2 months (95% confidence interval [CI]: 20.9–NA) for sustainable and 12.6 months (95% CI: 9.0–21.2) for unsustainable groups, respectively (p < 0.05). Multivariate analysis identified ECOG-PS:2 and fatigue, an adverse event, as independent predictors of unsustainable GNRI transition (95% CI: 1.29–90.6, odds ratio [OR]: 10.8; 95% CI: 1.06–26.9, OR: 5.34, respectively). Conclusion: : Sustaining a high level of GNRI was an important prognostic indicator in patients with mUC receiving first-line chemotherapy. Appropriate intervention for controlling adverse events, including fatigue, may enhance physical strength during cancer treatment.

Thoracic Radiotherapy in Extensive Disease Small Cell Lung Cancer: Multicenter Prospective Observational TRENDS Study.

(1) Introduction: Small cell lung cancer (SCLC) is an aggressive tumor type, accounting for about 15% of all lung cancers. Radiotherapy (RT) plays a fundamental role in both early and advanced stages. Currently, in advanced disease, the use of consolidative chest RT should be recommended for patients with good response to platinum-based first-line chemotherapy, but its use has not yet been standardized. The present prospective study aims to evaluate the pattern of care of consolidative chest RT in patients with advanced stage SCLC, and its effectiveness in terms of disease control and tolerability. (2) Materials and methods: This study was a multicenter prospective observational trial, proposed and conducted within the AIRO lung study group to evaluate the pattern of care of consolidative chest RT after first-line chemotherapy in patients with advanced SCLC. The patient and tumor characteristics, doses, fractionation and volumes of thoracic RT and prophylactic cranial irradiation (PCI), as well as the thoracic and extrathoracic response to the treatment, toxicity and clinical outcomes, were collected and analyzed. (3) Results: From January 2017 to December 2019, sixty-four patients were enrolled. Median follow-up was 33 months. The median age was 68 years (range 42-81); 38 patients (59%) were male and 26 (41%) female. Carboplatin + etoposide for 6 cycles was the most commonly used first-line therapeutic scheme (42%). With regard to consolidative chest RT, 56% of patients (35) received 30 Gy in 10 factions and 16 patients (26%) received 45 Gy in 15 sessions. The modulated intensity technique was used in 84.5% of cases, and post-chemotherapy macroscopic residual disease was the target volume in 87.5% of patients. Forty-four patients (69%) also underwent PCI. At the last follow-up, over 60% of patients did not experience chest disease progression, while 67% showed extrathoracic progression. At the first radiological evaluation after RT, complete response and stable disease were recorded in 6% and 46% of the cases, respectively. Two patients had a long-term complete response to the combined treatment. The brain was the first site of extrathoracic progression in 28%. 1y and 2y OS and PFS were 67%, 19%, 28% and 6%, respectively. Consolidative chest RT was well-tolerated in the majority of patients; it was interrupted in three cases (due to G2 pulmonary toxicity, disease progression and clinical decay, respectively). Only 1 patient developed G3 asthenia. (4) Conclusions: Consolidative chest RT has been shown to be useful in reducing the risk of thoracic disease progression and is absolutely well-tolerated in patients with advanced stage SCLC with good response after first-line chemotherapy. Among the Italian centers that participated in this study, there is still variability in the choice of fractionation and target volumes, although the guidelines contain clear recommendations. The aim of future research should be to clarify the role and modalities of chest RT in the era of immunotherapy in advanced-stage SCLC.

Pembrolizumab for first-line treatment of advanced unresectable or metastatic esophageal or gastroesophageal junction cancer.

Esophageal cancer (EC) is the seventh most common malignancy worldwide. Although systemic chemotherapy is the standard treatment for advanced EC, the available cytotoxic agents have limited efficacy. Pembrolizumab, a humanized monoclonal immunoglobulin G4 antibody that inhibits programmed cell death protein 1, has recently been developed for the treatment of patients with advanced EC. In the KEYNOTE-181 trial, pembrolizumab achieved a clinical meaningful overall survival benefit over chemotherapy alone when used as second-line treatment in patients with esophageal squamous cell carcinoma (ESCC) who had a combined positive score ⩾10 for expression of programmed death ligand 1. Furthermore, KEYNOTE-590 showed that pembrolizumab + chemotherapy was more effective than chemotherapy alone as first-line chemotherapy for patients with advanced EC. Accordingly, immune checkpoint inhibitor (ICI) chemotherapy has become the standard first-line treatment for advanced EC. The use of ICIs in primary therapy has helped to improve the prognosis, especially for ESCC. Moreover, in CheckMate 577, patients who received postoperative nivolumab therapy had a reduced risk of recurrence, and the ability of preoperative ICI chemotherapy to reduce the incidence of recurrence is now under investigation. This review outlines the evidence for use of pembrolizumab as a first-line treatment for advanced unresectable or metastatic EC, summarizes the ongoing research on ICI combination chemotherapy, and discusses the associated issues.