Difference In Disease Control Rate Research Articles

Significance of phosphoinositide 3-kinase inhibitors in advanced breast cancer: a systematic review and meta-analysis.

The Phosphoinositide 3-kinase (PI3K) inhibitors may be used in cancer progression and mortality along with standard therapy to improve therapeutic efficacy of Advanced Breast Cancer (ABC). This systematic review and meta- analysis were conducted to understand the therapeutic and toxicity profile of PI3K inhibitors in ABC. The electronic databases were searched for suitable trials as per the criteria. The outcomes assessed were Progression- Free Survival, Objective Response Rate and Disease Control Rate. The data were systematically reviewed and meta-analyzed by Mantele- Haenszel method. Seven studies were included in the systematic review and meta- analysis. The co- administration of PI3K inhibitors with standard therapy improved the Progression- Free Survival significantly, while a marginal improvement was observed in Objective Response Rate, no difference in Disease Control Rate and toxicity significantly increased. The addition of PI3K inhibitors decreased the risk of progression but increased the risk of toxicity.

Comparative efficacy of six programmed cell death protein-1 inhibitors in first-line treatment for advanced non-small cell lung cancer: A retrospective cohort study.

e14702 Background: All six programmed cell death-1 (PD-1) inhibitors (nivolumab, pembrolizumab, sintilimab, tislelizumab, toripalimab, and camrelizumab) have been used as first-line therapy in Chinese patients with advanced non-small cell lung cancer (NSCLC), but the comparative efficacy of these different drugs remains unclear. Methods: Retrospective collection of patient data from the First, Third, and Fifth Medical Centers of the Chinese PLA General Hospital who received PD-1 inhibitors (monotherapy or combination therapy) from June 2015 to April 2023. Analysis of patient clinical characteristics, treatment response, and survival outcomes was conducted, with the primary endpoints being overall survival (OS) and progression-free survival (PFS). Secondary endpoints include objective response rate (ORR) and disease control rate (DCR). Results: 913 patients were included and divided into 6 groups: nivolumab (123, 13.5%), pembrolizumab (421, 46.1%), sintilimab (239, 26.1%), tislelizumab (64, 7.0%), toripalimab (39, 4.3%), and camrelizumab (27, 3.0%). Median PFS was 16.0, 16.1, 18.4, 16.9, 23.7, and 12.8 months, and median OS was 33.7, 36.1, 32.5, not reached, 30.9, and 46.0 months for the nivolumab, sintilimab, pembrolizumab, tislelizumab, toripalimab, and camrelizumab groups, respectively. PFS and OS did not differ among the different PD-1 inhibitor groups (all P>0.05). There were differences in ORR among the different PD-1 inhibitors (P<0.05), but no differences in DCR (P>0.05). Conclusions: Nivolumab, pembrolizumab, sintilimab, tislelizumab, toripalimab, and camrelizumab exhibit similar efficacy in first-line treatment for patients with advanced NSCLC.

Association of PD-L1 expression and clinical outcomes in ROS1 - rearranged advanced non-small cell lung cancer treated with crizotinib.

Programmed cell death ligand 1 (PD-L1) is more readily expressed in ROS proto-oncogene 1 (ROS1) rearranged non-small cell lung cancer (NSCLC) compared to NSCLC cases lacking driver gene mutations. Prior research has established a link between PD-L1 expression and reduced effectiveness of EGFR or ALK inhibitors in EGFR or ALK-positive NSCLC. Nonetheless, the relationship between initial PD-L1 levels and the clinical impact of first-line crizotinib therapy in ROS1-rearranged NSCLC is still uncertain. From January 2016 to December 2021, a total of 246 patients with ROS1 positive tumors were collected. Out of these, 82 patients with advanced ROS1-rearranged NSCLC, who were treated with crizotinib as their initial therapy, were selected for the study. The study aimed primarily to evaluate the objective response rate (ORR) and progression-free survival (PFS), and secondarily to assess disease control rate (DCR) and overall survival (OS). Of the 82 advanced ROS1-rearranged NSCLC patients, 38 exhibited PD-L1 positivity, subdivided into 11 with high and 27 with low expression levels, while the remaining 44 showed no PD-L1 expression. The ORR for all included patients was 80.5%. No statistically significant variance in ORR was observed among ROS1-rearranged NSCLC patients across differing PD-L1 expression statuses. However, there was a statistically significant difference in DCR between PD-L1 negative group (100%) and high expression group (90.9%) (p=0.04). The median PFS spanned 26.4 months for the PD-L1 negative group, 16.6 for the low expression group, and 13.7 for the high expression group (p=0.001). Additionally, a notable statistical disparity was also observed in median PFS between the PD-L1 negative and positive groups (p=0.02). For the entire study population, the median OS was 53.0 months (95% CI 43.8 - 62.2). In the PD-L1-negative group, the median OS reached 57.2 months, compared to 53.0 months in the PD-L1-positive group, a difference lacking statistical significance (p=0.43). Our results suggest that for ROS1-positive NSCLC patients receiving crizotinib as first-line therapy, PD-L1 expression may serve as a negative prognostic marker for PFS rather than OS.

Clinical efficacy of different androgen deprivation therapies for prostate cancer and evaluation based on dynamic-contrast enhanced magnetic resonance imaging.

To evaluate the clinical efficacy of different androgen deprivation therapies for prostate cancer (PCa) based on dynamic-contrast enhanced magnetic resonance imaging (DCE-MRI). 104 patients with PCa were studied, all of whom were treated with androgen deprivation therapy. The patients were divided into a continuous group (continuous androgen deprivation therapy) and an intermittent group (intermittent androgen deprivation therapy) by random number table method, 52 cases/group. The therapeutic effect and DCE-MRI indices were compared and the relationship between DCE-MRI indices and clinical efficacy and the evaluation value of therapeutic efficacy were analyzed. The objective response rate (ORR) of the intermittent group was higher than that of the continuous group (p < 0.05), and there was no significant difference in disease control rate (DCR) between the two groups (p > 0.05). After treatment, volume transfer coefficient (Ktrans), reverse transfer constant (Kep), volume fraction (Ve), blood volume (BV), and blood flow (BF) in both groups were lowered, and those in the intermittent group were lower than the continuous group (p < 0.05). Ktrans, Kep, Ve, BF, and BV in the ORR group were lower than those in the non-ORR group (p < 0.05). Ktrans, Kep, Ve, BF, and BV were correlated with the therapeutic effect of PCa (p < 0.05). The AUC value of the combined detection of DCE-MRI indices in evaluating the therapeutic effect of PCa was greater than that of each index alone (p < 0.05). Compared with continuous androgen deprivation therapy, intermittent androgen deprivation therapy has better clinical efficacy in the treatment of PCa, and DCE-MRI indices are related to the treatment efficacy of PCa and have an evaluation value.

Improved clinical outcomes in advanced hepatocellular carcinoma treated with transarterial chemoembolization plus atezolizumab and bevacizumab: a bicentric retrospective study

PurposeThe aim of the present study was to assess the efficacy and safety of transarterial chemoembolization (TACE) combined with atezolizumab and bevacizumab (hereafter, TACE-Atez/Bev) in the treatment of advanced hepatocellular carcinoma (HCC) patients.Materials and methodsClinical information was collected from consecutive patients with advanced HCC who received treatment with TACE-Atez/Bev or Atez/Bev from April 2021 and October 2022. Treatment response, overall survival (OS), and progression-free survival (PFS) were the primary outcomes of this study. Adverse events (AEs) were the secondary outcomes. Propensity score matching (PSM) analysis was applied to reduce bias between two groups.ResultsThis study included 62 patients in the TACE-Atez/Bev group and 77 patients in the Atez/Bev group. The objective response rate (ORR) of the TACE-Atez/Bev group and the Atez/Bev group were 38.7% and 16.9% (P=0.004). However, there was no statistical difference in disease control rate between the two groups (69.4% vs 63.6%, P=0.479). Before PSM, the median OS was 14 months in the TACE-Atez/Bev group and 10 months in the Atez/Bev group (P=0.014). The median PFS in the TACE-Atez/Bev and Atez/Bev groups was 10 months and 6 months, respectively (P=0.001). After PSM, the median OS in the two groups was 14 months and 9 months, respectively (P=0.01). The median PFS was 7 months and 6 months, respectively (P=0.036). Multivariable analysis showed that treatment method was independent prognostic factors affecting OS.ConclusionsCompared with Atez/Bev treatment, TACE-Atez/Bev showed better OS, PFS, and ORR for Chinese patients with advanced HCC, with an acceptable safety profile.

Efficacy of Chemotherapy After Immune Checkpoint Inhibitor Discontinuation in Head and Neck Cancer.

Immune checkpoint inhibitors (ICI) have become widely used becuse of their effectiveness and relatively low rate of severe adverse events. However, active treatment should be continued after discontinuation of ICI as response rates are lower than that of conventional cytotoxic chemotherapy. The purpose of the present study was to determine the efficacy of treatment after ICI discontinuation. This was a retrospective study from hospital charts of 99 consecutive cases treated with ICI at our facility since 2017. Of these, 79 cases of squamous cell carcinoma which had already discontinued ICI were enrolled in the present study. After discontinuation of ICI, 40 cases received active treatment with salvage chemotherapy (SCTx; 33 cases) or surgery or radiotherapy (seven patients) and 39 cases received nonactive treatment. SCTx comprising paclitaxel and cetuximab (PTX-Cmab) was administered to 15 cases and other SCTx regimens to 18 cases. A significant increase in overall survival (OS) was observed with active treatment compared with nonactive treatment. No significant differences in OS or progression-free survival (PFS) were observed between SCTx regimens; however, there was a trend toward increased survival with PTX-Cmab. Univariate analysis of overall response rate (ORR) demonstrated significant differences in the site of disease at ICI and SCTx regimens. A significant difference in disease control rate was observed between SCTx regimens. Multivariate analysis of ORR demonstrated a significant correlation with PTX-Cmab treatment. Active treatment after ICI discontinuation and the use of PTX-Cmab as SCTx may increase OS in head and neck squamous cell carcinoma. 4 Laryngoscope, 134:228-235, 2024.

Efficacy and safety of hepatic artery infusion chemotherapy combined with tyrosine kinase inhibitors plus programmed death-1 inhibitors for hepatocellular carcinoma refractory to transarterial chemoembolization.

The subsequent therapy for hepatocellular carcinoma (HCC) patients with refractory to transarterial chemoembolization (TACE) is still controversial. This study was performed to evaluate the efficacy and safety of combination therapy comprising hepatic artery infusion chemotherapy (HAIC), lenvatinib, and programmed death-1 inhibitors relative to HAIC combined with lenvatinib. In this single-center retrospective study, we analyzed data from HCC patients with refractory to TACE from June 2017 to July 2022. Primary study outcomes were overall survival (OS) and progression-free survival (PFS), while the secondary outcomes were the objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events. We enrolled 149 patients finally, including 75 patients who received HAIC combined with lenvatinib plus PD-1 inhibitors therapy (HAIC+L+P group) and 74 patients who received HAIC combined with lenvatinib therapy (HAIC+L group). The median OS in the HAIC+L+P group (16.0; 95% CI: 13.6~18.3 months) was significantly higher compared to the HAIC+L group (9.0; 95% CI: 6.5~11.4 months) (p = 0.002), while the median PFS in the HAIC+L+P group (11.0; 95% CI: 8.6~13.3 months) was significantly higher compared to the HAIC+L group (6.0; 95% CI: 5.0~6.9 months) (p < 0.001). Significant between-group differences in DCR (p = 0.027) were found. Additionally, 48 pairs of patients were matched after propensity matching analysis. The survival prognosis between two groups before propensity matching is similar to that after propensity matching. Moreover, the percentage of patients with hypertension in the HAIC+L+P group was significantly higher compared to the HAIC+L group (28.00% vs. 13.51%; p = 0.029). A combination therapy of HAIC, lenvatinib, and programmed death-1 inhibitors significantly improved oncologic response and prolonged survival duration, showing a better survival prognosis for HCC patients with refractory toTACE.

Clinical Outcomes After Progression on First-Line Therapies in IDH1 Mutated Versus Wild-Type Intrahepatic Cholangiocarcinoma Patients.

Isocitrate dehydrogenase-1 (IDH1) mutations occur in a significant proportion of intrahepatic cholangiocarcinomas (iCCAs). No data are available regarding the prognostic impact of IDH1 mutations in advanced iCCA patients after progression on first-line therapies. We investigated the role of IDH1 mutation in advanced iCCA after progression on first-line therapies. After progression on first-line therapies for advanced iCCA, consecutive patients were retrospectively collected. The IDH1 status was tested at baseline. This analysis aimed to examine the association between the presence of IDH1 missense mutations and survival outcomes in patients with advanced iCCA treated with a second-line therapy. The analysis included 119 patients; 56/119 (47%) were IDH1 mutated (IDH1m) and 63/119 (53%) were IDH1 wild type (IDH1 WT). At univariate analysis for overall survival (OS), the presence of IDH1 mutation was associated with a worse median OS (mOS; 8.2 vs. 14.1 months; hazard ratio [HR] 1.9, 95% confidence interval [CI] 1.2-3.0, p=0.0047). Patients harboring IDH1 mutations showed a worse objective response rate (ORR) compared with patients without IDH1 mutation, whereas no significant differences in disease control rate (DCR) were found. Multivariate analysis confirmed IDH1 mutations as an independent negative prognostic factor for OS (HR 1.7, 95% CI 1.1-2.7, p=0.0256). By evaluating only patients receiving FOLFOX as second-line therapy, no statistically significant differences were found in terms of both OS and PFS between IDH1m and IDH1WT patients. In this subset of patients, those harboring an IDH1 mutation showed a worse ORR and DCR compared with those without. Finally, at univariate analysis for OS from third-line treatment, the presence of an IDH1 mutation was associated with a trend toward a worse mOS (6.0 vs. 11.9 months; HR 1.6, 95% CI 0.8-3.2, p=0.25). The present analysis constitutes the first evidence of a negative prognostic impact of IDH1 mutations in a cohort of patients treated after progression on first-line therapies in contrast to IDH1 inhibitors.

Efficacy and safety analyses of epidermal growth factor receptor tyrosine kinase inhibitors combined with chemotherapy in the treatment of advanced non–small-cell lung cancer with an EGFR/TP53 co-mutation

PurposeEpidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) combined with cytotoxic chemotherapy are highly effective in the treatment of advanced non–small-cell lung cancer (NSCLC) with EGFR mutations. The purpose of this study is to evaluate the efficacy and safety of this combination in advanced NSCLC patients with an EGFR/TP53 co-mutation.MethodsNinety-five advanced NSCLC patients with an EGFR/TP53 co-mutation were enrolled in this study. Treatments with either EGFR-TKI monotherapy (T group, n = 61) or EGFR-TKI combined with chemotherapy (TC group, n = 34) were evaluated in relation to objective response rate (ORR), disease control rate (DCR), median time to progression (TTP), and median overall survival (OS).ResultsThere were no statistically significant differences in DCR between the treatment groups. The ORR was significantly improved in the TC group versus the T group (55.9% vs. 34.4%, P = 0.042). A higher median TTP was noted in TC group compared with T group (16.1 vs. 11.1 months, P = 0.002). Patients without brain metastases in TC group had a longer median OS than in T group (48.4 vs. 28.8 months, P = 0.003). However, there was a non-significant trend towards longer OS in TC group in the entire cohort (36.9 vs. 28.2 months, P = 0.078). Cox multivariate regression analysis showed that clinical stage, brain metastases, EGFR21 L858R mutation, and T790M status at first progression were independent risk factors for OS. However, the incidence of grade 3 or higher adverse events were higher in the TC group than in the T group (32.4% vs. 13.1%, P = 0.025).ConclusionOur study indicates that EGFR-TKIs combined with chemotherapy could significantly improve the ORR and TTP of advanced NSCLC patients with an EGFR/TP53 co-mutation. Combination therapy may be a promising treatment for advanced NSCLC patients with an EGFR/TP53 co-mutation without brain metastases.

Real-World Data on Ramucirumab Therapy including Patients Who Experienced Two or More Systemic Treatments: A Multicenter Study.

Simple SummaryRamucirumab has been shown to be effective as a second-line agent after sorafenib in hepatocellular carcinoma (HCC) patients whose α-fetoprotein was ≥400 ng/mL. We performed a retrospective cohort study to investigate ramucirumab efficacy in a real-world setting. Progression-free survival (PFS) was consistent through treatment lines, modified albumin–bilirubin (mALBI) grade, Barcelona Clinic for Liver Cancer (BCLC) stage, and α-fetoprotein (AFP) level. By contrast, ascites was more frequently seen in mALBI 2b/3 patients and, therefore, should be carefully monitored.Background: The present study aimed to clarify the efficacy and safety of ramucirumab in a real-world setting, including patients who experienced two or more systemic treatments or whose hepatic reserve was deteriorated. Methods: In total, 79 patients with hepatocellular carcinoma (HCC) from 14 institutes throughout Japan were retrospectively analyzed. The response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and AEs were recorded according to the Common Terminology Criteria for AEs (CTCAE) version 5.0. Results: Median overall survival (OS) in the total cohort was 7.5 months (m). Median OS was 8.8 m in patients who were administered ramucirumab as a second-line treatment, while it was 7.3 m in third- or later-line treatment. Progression-free survival rates in the second- and third- or later-line therapies were 3.2 m and 3.2 m, respectively. The disease control rate (DCR) in the study was 43%. There were no statistically significant differences in DCR between the treatment courses. Regarding adverse events (AEs), the development of ascites was observed significantly more frequently in modified albumin–bilirubin (mALBI) 2b/3 patients than in mALBI 1/2a patients (54.5% vs. 25.0%, p = 0.03). Conclusions: Ramucirumab is useful as a second-line therapy and feasible as a third- or later-line treatment for HCC.

Trends of First-Line Targeted Therapy in Korean Patients With Metastatic Clear Cell Renal Cell Carcinoma: Sunitinib Versus Pazopanib, a Multicenter Study

Purpose: There have been few reports on comparison between sunitinib and pazopanib as first-line targeted therapy in Korean metastatic clear cell renal cell carcinoma (ccRCC). We sought to analyze the treatment trends of metastatic ccRCC by comparing the effects and adverse events of sunitinib and pazopanib.Materials and Methods: Data of 357 metastatic RCC patients who received the sunitinib or pazopanib as the first-line targeted therapy from the Daegyeong Oncology Study Group database was obtained and analyzed. Among these patients, patients who only clear cell type was confirmed after needle biopsy or nephrectomy were included, and patients who underwent target therapy for less than 3 months were excluded.Results: Of 251 patients who met the inclusion criteria, sunitinib and pazopanib group were identified in 156 (62%) and 95 patients (38%), respectively. Pazopanib group was older (66 years vs. 61 years, p=0.001) and more symptomatic (65% vs. 52%, p=0.037) and had more patients with Karnofsky performance status &lt;80 (20% vs. 11%, p=0.048) and fewer number of organ metastases (p=0.004) compared to sunitinib group. There was no significant difference in disease control rate (88.5% vs. 87.3%, p=0.744), the median progression-free survival (19 months vs. 15 months, p=0.444) and overall survival (25 months vs. 19 months, p=0.721) between sunitinib and pazopanib. The most common grade 3/4 adverse events with sunitinib and pazopanib were anemia (5%) and hand-foot syndrome (3%), respectively. There was no significant difference between sunitinib and pazopanib in number of patients who experienced grade 3/4 adverse events (15% vs. 11%, p=0.275). However, there were more patients who discontinued treatment due to only adverse events in sunitinib group compared to pazopanib group (12% vs. 3%, p=0.020).Conclusions: In Korean metastatic ccRCC, pazopanib tended to be used in patients with poorer health status compared to sunitinib. Sunitinib and pazopanib had no significant difference in treatment effect and survival, but pazopanib had more tolerable adverse events.

Efficacy and safety of low-dose apatinib plus S-1 versus regorafenib and fruquintinib for refractory metastatic colorectal cancer: a retrospective cohort study.

At present, regorafenib and fruquintinib are the standard regimens for refractory metastatic colorectal cancer patients in China, but both options have limited efficacy. The aim of this study was to investigate the efficacy and safety of low-dose apatinib plus S-1 compared with regorafenib and fruquintinib in patients with metastatic colorectal cancer (mCRC) refractory to standard therapies. The records of 114 patients with refractory mCRC in our center from April 2016 to September 2020 were retrospectively reviewed. Among these patients, 43 received apatinib 250 mg/day combined with S-1, 36 received regorafenib starting at 80 mg/day with weekly escalation, and 35 received fruquintinib 5 mg/day orally. Patients received radiographic examination every 1.5-2 months during the treatment period, progression-free survival time and overall survival time were analyzed and recorded. The baseline clinical characteristics of the patients were broadly similar among the three groups. The median progression-free survival (mPFS) was 3.9 months [95% confidence interval (CI): 2.5-5.3] in the apatinib plus S-1 group, 3.1 months (95% CI: 1.9-4.2) in the fruquintinib group, and 2.4 months (95% CI: 2.1-2.7) in the regorafenib group, the mPFS of apatinib plus S-1 was significantly longer than that of regorafenib (HR =0.49, P=0.003) and fruquintinib (HR =0.60, P=0.048). The median overall survival (OS) was 8.2 months (95% CI: 5.4-11.0) in the apatinib plus S-1 group, 7.8 months (95% CI: 5.3-10.3) in the fruquintinib group, and 7.5 months (95% CI: 4.2-10.7) in the regorafenib group, which was comparable among the 3 groups. There was no statistical difference in disease control rate (DCR) among the three groups. Patients in the apatinib plus S-1 group had a higher incidence of hematological toxicity including anemia (62.8%), neutropenia (30.2%), and thrombocytopenia (39.5%), and the hand-foot skin reaction (58.3%) was more prevalent in the regorafenib group, while the adverse reaction of hypertension (45.7%) in the fruquintinib group was very significant. Low-dose apatinib plus S-1 prolonged PFS compared with regorafenib and fruquintinib, and is a potential alternative regimen for the treatment of refractory mCRC with tolerable and controlled toxicity.

Ramucirumab for HCC patients who experienced two or more systemic therapy: A multicenter study.

395 Background: Ramucirumab has been approved for hepatocellular carcinoma (HCC) patients whose α-fetoprotein was≥400 ng/mL as a second-line agent after sorafenib. The present study aimed to clarify the efficacy and safety of ramucirumab including patients who experienced two or more systemic treatments or whose hepatic reserve was deteriorated. Methods: We enrolled 76 unresectable HCC patients from 14 institutes. The data, regarding survival, radiological response, and adverse events were retrospectively collected. This cohort included 35 patients who received more than two molecular targeted agents and 29 Child-Pugh B or C patients. The radiological response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Results: Median overall survival (OS) in the total cohort was 7.5 months (m), whereas it was 7.5 m, 9.8 m, and 6.8 m in patients who were administered ramucirumab as the second-, third-, and fourth-line therapies, respectively. The overall survival of Child-Pugh A patients (n = 47) was significantly longer than that of Child-Pugh B/C patients (n = 29) (OS 10.3 m vs. 6.7m, p = 0.04). Progression-free survival in the second-, third-, and fourth-line therapies was 3.7, 2.2, and 3.4 m, respectively. The best response identified by RECIST version 1.1 was partial response (PR) in one patient and stable disease (SD) in 25 patients, and the disease control rate (DCR) in the study was 49.1%. There were no statistically significant differences in DCR between the treatment courses. Regarding adverse events, there was no difference between the treatment courses. However, peripheral edema, the development of ascites that required the administration of diuretics (Grade ≥ 2), and diarrhea were significantly more frequent in Child-Pugh B/C patients than in Child-Pugh A patients (peripheral edema; 65.5% vs . 31.9%, p = 0.005, ascites; 62.0% vs . 19.1%, p &lt; 0.001, diarrhea; 27.6% vs . 8.5%, p = 0.05). Conclusions: Ramucirumab was useful as a second-line therapy and feasible as a third- or fourth-line treatment for HCC.

Real-world effectiveness of anlotinib in combination with PD-1 inhibitors as second-line or later therapy for advanced or metastatic esophageal squamous cell carcinoma.

320 Background: Anti-PD-1 mAb treatment has been shown to be effective in the treatment of esophageal cancer. Anlotinib has been approved in China as a second-line treatment for advanced esophageal cancer because of its good tolerance and efficacy. In the treatment of esophageal cancer, antiangiogenic target therapy combined with immunotherapy has been preliminarily recognized internationally. The purpose of this study is to investigate the efficacy and safety of anlotinib in combination with PD-1 inhibitors in second-line or later therapy during the treatment of esophageal cancer in the real world setting.(A LOT-EC3, NCT04966611). Methods: This is a prospective, multicenter real-world study. The esophageal cancer patients who received anlotinib in combination with PD-1 inhibitors in second-line or later therapy were enrolled. The primary endpoint was PFS (progression-free survival), and secondary endpoints were ORR (objective response rate), DCR (disease control rate) and OS (overall survival). The response to treatment was evaluated according to RECIST version 1.1. In addition, adverse events were evaluated by CTCAE v5.0. Results: From Jul 2020 to Sep 2021, 40 patients with a median age of 65.5 (range: 48̃81) were enrolled, in which the metastasis of more than 1 organ occurred in 62.5% of the 40 patients; the metastasis of more than 2 organs occurred in 37.5% (15 patients). 26 (65.0%) and 14 (35.0%) patients received anlotinib combined with PD-1 inhibitors as second line and third &amp; above line therapy, respectively. Among all patients, 1 patient achieved complete response (CR), 11 patients partial response (PR), 23 patients stable disease (SD), illustrating an ORR of 30.0% and a DCR of 87.5%. In the second line therapy, ORR was 30.8 %, DCR was 92.3%. In the third &amp; above line, ORR with 28.6%, DCR with 78.6% was observed. Median PFS was not reached. For all the 40 patients, 27 of which were treated with Camrelizumab, 10 were treated with Sintilimab, other 3 patients were treated with other kinds of PD-1 inhibitors. There was no significant difference in DCR between different PD-1 inhibitors. Treatment related adverse events (trAEs) occurred in 22 (55%) patients. 4 patients had grade 3 or more trAEs. No patient died due to trAE. Conclusions: Anlotinib combined with PD-1 inhibitors is found to be a reasonable option in second-line or later therapy for the treatment of advanced esophageal cancer. To our best knowledge, this is the first summarized real-world study on anlotinib combined with PD-1 inhibitors in advanced esophageal cancer. The treatment effects are similar to the outcomes in comparable clinical trials, which support the further recommendation of anlotinib combined with PD-1 inhibitors in the treatment of esophageal cancer. Clinical trial information: NCT04966611.

Effect of capecitabine combined with irinotecan on the safety of colon cancer treatment, patients’ adverse reactions and quality of life

Purpose: To study the impact of the combination of capecitabine and irinotecan on the safety of colon cancer treatment, adverse reactions and wellbeing of patients.Methods: Colon cancer subjects (n =120) admitted to Guangzhou First People’s Hospital, Guangzhou, China were assigned equally to two groups (A and B) according to their order of admission, and they received intravenous infusion of irinotecan. In addition, group A patients were administered capecitabine, but those in B group were given tegafur, gimeracil and oteracil porassium. The patients in groups A and B were compared with respect to the incidence of unwanted effects, quality of life (QoL), and overall clinical efficacy of the treatments.Results: Cases of nausea and vomiting, delayed diarrhea and sensory neuropathy of the patients were significantly reduced in group A, relative to group B. Moreover, QoL score after treatment was markedly higher in group A than in group B, while the objective response rate (ORR) of colon cancer patients in group A was also significantly higher than that in group B (p &lt; 0.05). However, no obvious difference in disease control rate (DCR) was observed between groups A and B (p &gt; 0.05).Conclusion: Combined capecitabine and irinotecan therapy effectively improves clinical prognosis, reduces the incidence of adverse reactions, and is safe in colon cancer patients. Therefore, the combined treatment may be beneficial in the management of colon cancer.

Camrelizumab Plus Sorafenib Versus Sorafenib Monotherapy for Advanced Hepatocellular Carcinoma: A Retrospective Analysis.

BackgroundHepatocellular carcinoma (HCC) is a highly aggressive malignancy with poor prognosis. Immunotherapy has gained great interest for various solid tumors due to its promising clinical efficacy. Targeted therapy also plays a crucial role in anticancer treatment. However, studies on the combination of immunotherapy and targeted therapy for advanced HCC are limited. Thus, the objective of this study was to investigate the efficacy and safety of camrelizumab combined with sorafenib in the treatment of advanced HCC.MethodsFrom January 2019 to January 2021, 100 consecutive patients with advanced HCC in our hospital were enrolled for this study. Patients were assigned into two groups: a combined-therapy group (camrelizumab + sorafenib) and a sorafenib-only group. Progression-free survival (PFS), overall survival (OS), treatment response, and relevant adverse effects (AEs) were evaluated and recorded.ResultsOf a total of 100 patients, 35 received a combination of camrelizumab and sorafenib, and 65 were treated with sorafenib alone. After 1:1 propensity score matching (PSM), each group had 34 patients. The overall response rate (ORR) of the combined-therapy group was statistically significantly higher than that of the sorafenib-only group (before PSM, p = 0.037; after PSM, p = 0.010). However, there was no significant difference in disease control rate (DCR) between the two groups (before PSM, p = 0.695; after PSM, p = 1.000). Patients who received the combination therapy had significantly longer PFS than those who received the sorafenib monotherapy (before PSM, p = 0.041; after PSM, p = 0.043). However, the two groups exhibited comparable median OS (before PSM, p = 0.135; after PSM, p = 0.105). Although the combined-therapy group showed a higher incidence of AEs such as thrombocytopenia than the sorafenib-only group after PSM, most of these AEs were easily controlled after treatment.ConclusionCamrelizumab plus sorafenib showed favorable efficacy and manageable toxicity for patients with advanced HCC. However, more prospective randomized trials are necessary to further verify the potential clinical benefits of this combination therapy.

Correlation between MTHFR 677C &gt; T polymorphism and response of pemetrexed-based chemotherapy in advanced NSCLC: A meta-analysis

Abstract Objective The aim of this study was to investigate the correlation between MTHFR 677C &gt; T polymorphism and response of pemetrexed-based chemotherapy in advanced non-small-cell lung cancer (NSCLC) by pooling the open published relevant studies. Methods Clinical studies associated with MTHFR 677C &gt; T polymorphism and response of pemetrexed-based chemotherapy in advanced NSCLC were systematically searched in databases of Pubmed, Embase, Cochrance Library, China national knowledge infrastructure (CNKI) and Wanfang. The correlation was expressed by odds ratio (OR) and corresponding 95% confidence interval (95% CI). The publication bias of the included studies was evaluated through Begg’s funnel plot and Egger’s line regression test. Results Ten prospective clinical studies relevant to MTHFR 677C &gt; T polymorphism and response of pemetrexed-based chemotherapy in NSCLC were included in the present meta-analysis. The pooled results indicated that the partial response in NSCLC patients with TT or CT genotype was inferior to CC genotype in a dominant gene model (TT + CT vs CC) (OR = 0.16, 95% CI: 0.06–0.41, P = 0.001). NSCLC cases with T genotype were inferior to C genotype in the objective response rate treated with pemetrexed-based chemotherapy for dominant (OR = 0.28, 95% CI: 0.18–0.45, P = 0.001), recessive (OR = 0.43, 95% CI: 0.19–0.94, P = 0.03) and homozygous models (OR = 0.30, 95% CI: 0.13–0.67, P = 0.003). However, there was no statistical difference in disease control rate, progressive disease between different genotypes of different gene models (P all &gt; 0.05). Conclusion The pemetrexed-based chemotherapy response was decreased in NSCLC cases with T genotype, which can be applied as a potential pemetrexed-based chemotherapy response marker.

Plasma pre-treatment T790M relative allelic frequency in patients with advanced EGFR-mutated non-small cell lung cancer predicts treatment response to subsequent-line osimertinib.

BackgroundApproximately half of all patients with advanced EGFR-mutant NSCLC will develop acquired resistance to first or second-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs) with a T790M mutation. In the AURA3 trial, patients with a T790M mutation had a response rate of 71% to osimertinib, a third-generation EGFR-TKI. The response to osimertinib may vary according to plasma T790M mutation frequency. Our aim was to determine the effect of plasma T790M mutation load on treatment response to osimertinib in an Australian multi-institutional cohort.MethodsWe performed a retrospective study on patients treated with osimertinib in the second-line setting and beyond between 2016–2018 from ten centres in Australia, who had T790M mutations detected in tumour or plasma. The primary objective was to investigate if there was a difference in disease control rate (DCR) between patients with high vs. low T790M relative allelic frequency (RAF) as detected in plasma, using a 0.3 RAF cut-off, as determined by ddPCR or BEAMing PCR. Secondary objective was to determine the survival outcomes according to high versus low plasma T790M RAF. Additional analyses were performed to investigate the survival outcome for patients with plasma versus tissue T790M positivity.ResultsA total of 139 patients were included in this study. Patients with higher RAF demonstrated higher DCR (74% vs. 36%, P=0.02), however there was no statistically significant difference in survival outcomes in the two groups. Exploratory analysis showed that patients with tissue T790M+ had improved DCR compared with those with plasma T790M+ (89% vs. 68%, P=0.01) and longer progression free survival (median 15.4 vs. 9.7 months; HR 0.51, 95% CI: 0.34 to 0.77, P=0.003) and overall survival (median not reached, HR 0.51, 95% CI: 0.30 to 0.86, P=0.02). Patients who were tissue T790M+ demonstrated superior survival compared to plasma T790M+ after correcting for confounding variables in a multivariate model.ConclusionsDCR was superior in patients with higher plasma T790M mutation load versus lower plasma T790M mutational load, without significant survival benefit. Plasma T790M RAF is a potential predictive biomarker which should be investigated and validated in larger prospective studies.

Clinical efficacy of systemic chemotherapy combined with radiofrequency ablation and microwave ablation for lung cancer: a comparative study

Objective Local thermal ablation, a minimally invasive technique, has been widely used in clinical treatment of lung cancer. This study aimed to discuss the clinical efficacy of systemic chemotherapy combined with radiofrequency ablation (RFA) versus systemic chemotherapy combined with microwave ablation (MWA) in treating lung cancer. Methods A retrospective analysis involving 124 lung cancer patients, who received RFA (n = 68) and MWA (n = 56) combined with systemic chemotherapy in Cangzhou People’s Hospital from August 2017 to December 2019, was conducted. Before comparative analysis for therapeutic efficacy, the two groups of patients were matched with propensity score matching method at a ratio of 1:1. Indicators including progression-free survival (PFS), overall survival (OS), short-term efficacy, tumor marker level, local tumor control rate, and postoperative complications were comparatively analyzed. Results There was no statistical difference in disease control rate and objective response rate (90.6% and 78.1% vs 93.8% and 84.4%) between RFA group and MWA group. The incidence of complications was 12.5% in RFA group and 18.8% in MWA group with no statistically significant difference. In addition, the local tumor control rate in MWA group (90.6%) was significantly higher than that in RFA group (78.1%). Regarding survival, a statistically significant difference was observed in median PFS of RFA and MWA groups (9.2 months vs 10.4 months, p < 0.05), while OS in two groups slightly varied. Conclusion MWA was superior to RFA over local tumor control rate and PFS and showed great potential in lung cancer ablation treatment.

The Effect of Nano-Albumin Paclitaxel on the Early Postoperative Recurrence of Primary Liver Cancer.

This study aimed at investigating the clinical effect and safety of albumin binding paclitaxel (Nab-P) for the first-line treatment of advanced primary liver cancer. Clinical data of 23 patients with primary liver cancer, who were treated in the first-line tumor treatment Department in the PLA General Hospital from May 2014 to December 2015, were analyzed retrospectively. The patients were divided into an observation group and a control group, according to their treatment plan. The patients in the observation group (12) received Nab-P treatment (5 cases of Nab-P combined with tegeor, 5 cases of Nab-P combined with capecitabine, and 2 cases of Nab-P single drug), and the patients in the control group (11) received gemcitabine combined with oxaliplatin. Each treatment cycle lasted for 21 days, and the treatment effect was evaluated once every two cycles, while the adverse reactions were assessed after every cycle. The survival rates of the different groups were compared using the chi-square test or the Fisher's exact test, the Kaplan Meier survival curve, and the log rank test. Results from all patients were used to evaluate treatment efficacy and adverse reactions. In the observation group, there were 2 cases of partial remission, 7 cases of disease stability, and 3 cases of disease progress; in the control group, there were 2 cases of partial remission, 5 cases of disease stability, and 4 cases of disease progress. There was no significant difference in disease control rate between the two groups (75% vs. 64%, χ² = 0.350, P > 0.05). There was no significant difference in the median progression free survival time between the two groups (5.1 (2.7-6.7) months versus 4.3 (2.5-54) months, χ² =0.647, P > 0.05). No serious side effects were observed in any of the two groups. Among the observed side effects were some PLT toxicity and increased AST (Aspartate transaminase) incidence, which showed a statistically significant difference between the two groups (χ² = 5.490, P = 0.036 for PLT; χ² = 6.135, P = 0.027 for AST). The new Nab-P-based drug regimen has a good effect against primary liver cancer, and the side effects are tolerable. However, the sample size used in this study was small and further clinical studies using larger samples are required to verify the results.