Terms Of Objective Response Rate Research Articles

Inflamed immune phenotype predicts favorable clinical outcomes of immune checkpoint inhibitor therapy across multiple cancer types

BackgroundThe inflamed immune phenotype (IIP), defined by enrichment of tumor-infiltrating lymphocytes (TILs) within intratumoral areas, is a promising tumor-agnostic biomarker of response to immune checkpoint inhibitor (ICI) therapy. However, it...

Single-center analysis on a real-world cohort of patients with metastatic urothelial carcinoma studied by NGS: Molecular landscape and efficacy of targeted therapies.

661 Background: the median overall survival (OS) in metastatic urothelial carcinoma (mUC) treated with multiagent therapy is approximately 13 months (mo). Around 69% of these tumors harbor potential therapeutic targets. Real-world evidence on using Next Generation Sequencing (NGS) in mUC management is limited. Methods: we conducted a single-center analysis on a real-world cohort of patients (pts) with mUC. The study population included pts aged >18 years with diagnosis of mUC studied by NGS at the moment of starting immunotherapy (enrollment period: 09/04/2019 – 03/25/2022). Median OS and median progression-free survival (PFS) were determined using Kaplan-Meier curves. Results: we included 43 pts. Median age at mUC diagnosis was 67 years; 38 (88.4%) pts were men; 38 (88.4%) pts were ECOG 0-1 at mUC diagnosis; one or more adverse prognostic factors (Bellmunt Risk Score) were identified in 33 (76.7%) pts; primary tumor site was lower tract in 36 (83.7%) pts. All pts were treated with platinum-based combinations (neoadyuvant, adyuvant or first line) and immunotherapy. Pathogenic alterations were found in 25 (58.1%) pts. In the group of 25 pts with pathogenic alterations, 17 pts progressed to immunotherapy and 7 pts of them received targeted therapies; 10 pts could not receive targeted therapies due to poor prognosis. In the group of 18 pts without pathogenic alterations, 11 pts progressed to immunotherapy and 8 pts of them received other chemotherapy options; 3 pts could not receive other chemotherapy options due to poor prognosis. The median OS (time since mUC diagnosis) among 25 pts with pathogenic alterations was 30.2 (CI 95%: 18.9-41.5) mo compared to 22.9 (CI 95%: 12-33.9) mo among 18 pts without pathogenic alterations, (p = 0.557). Focusing on the subgroup of 7 pts treated with targeted therapies (Table), we found an objective response rate (ORR) of 42.9%; the median PFS was 7.3 (CI 95%: 6.7-7.9) mo and the median OS (time since beginning targeted therapies) was 10.9 (CI 95%: 2.4-19.5) mo. Conclusions: We recommend that all pts with mUC undergo NGS at the time of diagnosis, given the high percent (58.1%) of pathogenic alterations in our real-world cohort and the efficacy in terms of ORR, PFS and OS in pts treated with targeted therapies. [Table: see text]

Durvalumab with or without tremelimumab for patients with recurrent or metastatic squamous cell carcinoma of the head and neck: a systematic review and meta-analysis.

Head and neck squamous cell carcinoma (HNSCC) ranks as the sixth most prevalent cancer worldwide, significantly impacting patients' quality of life. Immune checkpoint inhibitors (ICI) have been employed in the treatment of recurrent/metastatic (R/M)-HNSCC patients. This meta-analysis aims to assess the efficacy and safety of durvalumab monotherapy compared to the combination of durvalumab and tremelimumab in R/M-HNSCC patients. Relevant studies were systematically searched in PubMed, Embase, and Cochrane Library databases. All articles comparing durvalumab monotherapy with the combination with durvalumab and tremelimumab in R/M-HNSCC treatment were included. Additionally, the references of identified studies were screened if necessary. A total of 1298 patients from three studies comparing durvalumab with durvalumab and tremelimumab in treating R/M-HNSCC were include in this meta-analysis. Our findings revealed no significant difference in objective response rate (ORR) [odds ratio (OR): 1.15, 95% confidence interval (CI): 0.85 to 1.56, P = 0.36] and disease control rate (DCR) (OR=1.08, 95%CI: 0.86 to 1.37, P = 0.51). Similar outcomes were observed in overall survival (OS), progression-free survival (PFS), and duration of response (DoR). Regarding safety, there was no significant difference in the incidence of treatment-related adverse events (trAEs) between the two groups (OR=1.26, 95%CI: 0.81 to 1.94, P = 0.30). However, patients treated with the combination therapy exhibited a higher incidence of grade 3-4 trAEs (OR=1.93, 95%CI: 1.36 to 2.73, P = 0.0002) and a greater likelihood of discontinuing treatment due to trAEs (OR=2.07, 95%CI: 1.12 to 3.85, P = 0.02). There was no significant difference in the occurrence of severe trAEs leading to death (OR=1.36, 95%CI: 0.47 to 3.96, P = 0.57). This meta-analysis suggests that R/M-HNSCC patients receiving the combination of durvalumab and tremelimumab may achieve comparable outcomes in terms of ORR, DCR, OS, PFS, and DoR, without significant differences. However, the combination therapy is associated with a higher incidence of grade 3-4 trAEs and an increased likelihood of treatment discontinuation due to trAEs. These findings highlight the need for cautious consideration of the combination of durvalumab and tremelimumab in R/M-HNSCC patients, which should be further evaluated in high-quality studies.

Third-line Treatment for Metastatic Triple-negative Breast Cancer: A Systematic Review and Network Meta-analysis.

Metastatic triple-negative breast cancer (mTNBC) is an invasive histologic subtype with a poor prognosis and rapid progression. Currently, there is no standard therapy for the third-line treatment of mTNBC. In this study, we conducted a network meta-analysis to compare regimens and determine treatment outcomes. We performed a systematic search of PubMed, EMBASE, the Cochrane Central Register of Controlled Bases, and the minutes of major conferences. Progression-free survival, overall survival, and objective response rate were analyzed through network meta-analysis using the R software (R Core Team). The efficacy of the treatment regimens was compared using hazard ratios, odds ratios, and 95% CIs. We evaluated 15 randomized controlled trials involving 6,010 patients. Compared with the physician's choice treatment, sacituzumab govitecan showed significant advantages in progression-free survival and overall survival, with hazard ratio values of 0.41 (95% CI: 0.32-0.52) and 0.48 (95% CI, 0.39-0.60). In terms of objective response rate, sacituzumab govitecan is the best-performing therapy (odds ratio: 10.82; 95% CI: 5.58-20.97). Adverse events among grades 3 to 5 adverse reactions, the incidence of neutropenia and leukopenia in each regimen was higher, whereas the incidence of fever, headache, hypertension, and rash was lower. Compared with the treatment of the physician's choice, sacituzumab govitecan appears more efficacious and is the preferred third-line treatment for mTNBC.

Dual-Targeting Nanoliposome Improves Proinflammatory Immunomodulation of the Tumor Microenvironment.

Immunotherapies targeting immune checkpoints have revolutionized cancer treatment by normalizing the immunosuppressive microenvironment of tumors and reducing adverse effects on the immune system. Indoleamine 2,3-dioxygenase (IDO) inhibitors have garnered attention as a promising therapeutic agent for cancer. However, their application alone has shown limited clinical benefits. Cabozantinib, a multitarget tyrosine kinase inhibitor, holds immunomodulatory potential by promoting infiltration and activation of effector cells and inhibiting suppressive immune cells. Despite its potential, cabozantinib as a monotherapy has shown limited efficacy in terms of objective response rate. In this study, IDO-IN-7 and cabozantinib are coencapsulated into liposomes to enhance tumor accumulation and minimize adverse effects. The liposomal combination exhibits potent cytotoxicity and inhibits the function of IDO enzyme. Furthermore, the dual-targeted treatment effectively inhibits tumor development and reverses the suppressive tumor microenvironment by regulating both adaptive and innate branch of immune system. This is evidenced by pronounced infiltration of T cells and B cells, a decrease of regulatory T lymphocytes, a shift to a proinflammatory phenotype of tumor-associated macrophages, and increases levels of neutrophils. This is the first developed of a liposome-delivered combination of IDO inhibitors and cabozantinib, and holds great potential for future clinical application as a promising anticancer strategy.

Immune Checkpoint Inhibitors Serve as the First-Line Treatment for Advanced Head and Neck Cancer.

Immune checkpoint inhibitor (ICI) therapy has demonstrated substantial benefits for certain patients. We try to evaluate the merits and demerits of each immunotherapy to aid clinical treatment. We conducted a comprehensive search of the PubMed, Embase, and Cochrane databases for randomized clinical trials published as of June 10, 2023. Our study included published clinical trials of ICI monotherapy or combination therapy, along with data on treatment-related adverse events (TRAE). Data regarding survival efficacy and adverse events of each randomized controlled trial (RCT) were collected. The Bayesian random effects model was utilized for the network meta-analysis (NMA). This study incorporated 19 RCTs, involving 5900 patients. Among 14 treatment regimens, Pembrolizumab combined with chemotherapy emerged as the most promising primary treatment for overall survival (OS) and objective response rate (ORR). Toripalimab combined with chemotherapy exhibited the highest likelihood of becoming the primary treatment for extending progression-free survival (PFS). Durvalumab showed the lowest probability of adverse events, suggesting a safer profile compared with other drugs. Camrelizumab combined with chemotherapy demonstrated a heightened risk of adverse events. Dual ICI Nivolumab/Ipilimumab surpassed Durvalumab/Tremelimumab in terms of ORR and adverse events. The standard of care (SOC) regimen did not exhibit strong performance across the four outcome indicators. Our analysis suggests that the integration of chemotherapy agents with ICIs enhances its efficacy as a first-line treatment for patients with advanced head and neck cancer (HNC). 1 Laryngoscope, 134:749-761, 2024.

Effect of the combination of trastuzumab, paclitaxel and carboplatin in the treatment of uterine serous carcinoma: A systematic review and meta-analysis

Purpose: To systematically review the efficacy of paclitaxel-carboplatin versus trastuzumab in combination with paclitaxel/carboplatin for the treatment of uterine serous carcinoma (USC) with high Her2/neu expression, in order to obtain an evidence-based reference for clinical treatment.Methods: Publications were obtained from China Knowledge Network (CNKI), VIP database (VIP), Wanfang database, PubMed, Embase, Cochrane Library, and Web of Science. The retrieval period was from the establishment of database to May 2022, and the efficacy of paclitaxel-carboplatin combination with trastuzumab (study group) versus paclitaxel-carboplatin (control group) for the treatment of Her2/neu high-expressing USC was collected. Two reviewers independently screened, extracted data, and evaluated the quality of evidence of included studies. RevMan 5.3 statistical software was used for meta-analysis. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events.Results: Meta-analysis showed that the study group had significantly longer OS than control group (p = 0.004), and PFS of study group was significantly longer than that of control group (p < 0.0001). In terms of ORR, there was no difference between the two groups (p = 0.42). However, in terms of total and high-risk adverse events, the number of patients with adverse events in study group was higher than in control group (p = 0.05), (p = 0.0001).Conclusion: Paclitaxel-carboplatin combination with trastuzumab significantly prolongs OS and PFS in USC patients with high Her2/neu expression, but it may increase the incidence of adverse events.

Trastuzumab deruxtecan heralds new era in the treatment of metastatic breast cancer

Trastuzumab deruxtecan is a new generation Her2-directed antibody-cytostatic conjugate. The unique structure of the molecule, innovative pharmacokinetic and pharmacodynamic properties of the drug allows its effect to be extended not only to the target cells, but also to nearby tumour cells, causing their death. This phenomenon has become known as the abscopal effect, due to which the drug demonstrates effectiveness regardless of the degree of Her2 expression. In clinical trials, trastuzumab deruxtecan therapy significantly outperformed the standard treatment options in patients with Her2-positive breast cancer. Thus, the median time to progression was 17.8 months in patients who were exposed to multiple lines of therapy, including trastuzumab-emtansine, vs 6.9 months in the control group treated with the combination of capecitabine and anti-Her2 agents (RR 0.36, 95% CI 0.28–0.45), which has resulted in a significant prolongation of patients’ lives. The median overall survival reached 39.2 months, while it remained at the level of 26.5 months in the control group (RR 0.6575; 95% CI 0.5023–0.8605; p = 0.0021). In a direct comparison of treatment, trastuzumab deruxtecan was superior to trastuzumab emtansine, significantly increasing the median progression-free survival by 4 times: 28.8 vs. 6.8 months (RR 0.33, 95% CI 0.26–0.43). It also had advantages in terms of objective response rates, quality of life measures, and overall survival. Trastuzumab deruxtecan demonstrated high efficacy in the treatment of HER2-low tumours (Her2-low mBC), surpassing the standard chemotherapy options in all evaluated parameters in pre-treated patients. This article presents the results ofthe main clinical trials of trastuzumab derukstecan, additionally discusses its efficacy in CNS metastatic lesions, highlights the safety issues of the drug.

Idarubicin versus epirubicin in drug-eluting beads-transarterial chemoembolization for treating hepatocellular carcinoma: A real-world retrospective study.

The purpose of this study was to compare the efficacy and safety of idarubicin-loaded drug-eluting beads-transarterial chemoembolization (IDA-TACE) and epirubicin-loaded drug-eluting beads-TACE (EPI-TACE) in treating hepatocellular carcinoma (HCC). All patients with HCC treated with TACE in our hospital between June 2020 and January 2022 were screened. The included patients were divided into the IDA-TACE group and EPI-TACE group to compare overall survival (OS), time to progression (TTP), objective response rate (ORR), and adverse events. There were 55 patients each in the IDA-TACE and EPI-TACE groups. Compared with the EPI-TACE group, the median TTP in the IDA-TACE group was not significantly different (10.50 vs. 9.23months; HR 0.68; 95% CI 0.40-1.16; P = 0.154), whereas the survival status in the IDA-TACE group tended to be better (neither achieved; HR 0.47; 95% CI 0.22-1.02; P = 0.055). Based on the Barcelona Clinic Liver Cancer staging system for subgroup analysis, considering stage C patients, the IDA-TACE group performed significantly better in terms of ORR (77.1% vs. 54.3%, P = 0.044), median TTP (10.93 vs. 5.20months; HR 0.46; 95% CI 0.24-0.89; P = 0.021), and median OS (not achieved vs. 17.80months; HR 0.41; 95% CI 0.18-0.93; P = 0.033). Considering stage B patients, there were no significant differences between the IDA-TACE and EPI-TACE groups in terms of ORR (80.0% vs. 80.0%, P = 1.000), median TTP (10.20 vs. 11.2months; HR 1.41; 95% CI 0.54-3.65; P = 0.483), or median OS (neither achieved, HR 0.47; 95% CI 0.04-5.24; P = 0.543). Notably, leukopenia was more common in the IDA-TACE group (20.0%, P = 0.052), and fever was more common in the EPI-TACE group (49.1%, P = 0.010). IDA-TACE was more effective than EPI-TACE in treating advanced-stage HCC and comparable in treating intermediate-stage HCC.

Efficacy and Safety of Low-Dose Apatinib Combined with Chemotherapy as Second-Line Treatment for Advanced Gastric Cancer: A Meta-Analysis

Introduction: At present, there are several studies on low-dose apatinib combined with chemotherapy as a second-line treatment of advanced gastric cancer (AGC), but the conclusions are controversial. Therefore, this meta-analysis aimed to evaluate the efficacy and safety of low-dose apatinib combined with chemotherapy as a second-line treatment of AGC. Methods: Nine databases were searched for records on apatinib combined with chemotherapy in treating AGC from inception to June 2022. The observation group received low-dose apatinib combined with chemotherapy, while the controls received chemotherapy alone or other non-placebo treatments. Outcomes included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events. The relative risk (RR) and weighted mean difference (WMD) were used as effect sizes. Results: Eight studies involving 679 patients were included in this meta-analysis. The results of the meta-analysis showed that the observation group was superior to the controls in terms of ORR (RR = 1.38, 95% confidence interval [CI]: 1.05–1.81, p = 0.02), DCR (RR = 1.35, 95% CI: 1.20–1.53, p < 0.001), OS (WMD = 4.72, 95% CI: 0.71–8.72, p < 0.001), and PFS (WMD = 2.67, 95% CI: 1.7–3.63, p < 0.001). There were no significant differences between the two groups in adverse events of any grade except hypertension (RR = 2.82, 95% CI: 2.07–3.84, p < 0.001), hand-mouth syndrome (RR = 1.84, 95% CI: 1.84–2.48, p < 0.001), and proteinuria (RR = 3.63, 95% CI: 2.31–5.7, p < 0.001). Conclusion: Low-dose apatinib combined with chemotherapy as a second-line therapy is more effective in improving the efficacy of AGC compared to chemotherapy alone. However, this option has the potential to increase the risk of hypertension, hand-mouth syndrome, and proteinuria.

Tarlatamab in small cell lung cancer (SCLC): Safety and efficacy analyzed by baseline brain metastasis.

8582 Background: Tarlatamab, a BiTE molecule targeting DLL3 and CD3, is being studied in patients (pts) with extensive stage small cell lung cancer (ES-SCLC).1 Up to 25% of pts diagnosed with SCLC have brain metastases (BM) and 50% or more will develop BM during the course of the disease. Pts with ES-SCLC and BM have poor prognosis and quality of life. We analyzed the characteristics and outcomes of pts included in the tarlatamab phase 1 study (NCT03319940) who had baseline BM vs those who did not. Methods: Pts included in the phase 1 trial had SCLC that progressed after ≥1 platinum-based regimen and received tarlatamab (0.003–100 mg IV). Pts with treated BM were eligible if local therapy was delivered ≥ 2 weeks prior to first tarlatamab dose. Results: As of 03 January 2023, 192 pts had received tarlatamab as monotherapy. Median age was 62 (range, 32–80) y; 188 pts (98%) had ECOG PS 0–1 and median prior therapy lines was 2 (range, 1–6), with 107 pts (56%) receiving prior anti-PD1/PD-L1. 48 pts (25%) had BM at screening and 142 (74%) did not (No BM); data was missing for 2 pts (1%). Pts with BM were more likely to have received &gt; 3 prior lines of therapy (BM, 29%; No BM, 9%) and have a record of prior brain radiation (BM, 85%; No BM, 40%); otherwise, characteristics of pts with BM were generally similar to those without. Tarlatamab delivered comparable activity in pts with BM vs. those without in terms of objective response rate (ORR; 20%, 25%) and disease control rate (DCR; 59%, 50%) (Table). Median duration of response (DoR) was 14.9 months (BM) vs. 13.0 months (no BM). Median overall survival (OS) was 13.2 months in the BM group vs 15.5 months in the no BM group. Safety outcomes were similar in terms of treatment-related AEs (TRAEs; BM, 90%; No BM, 94%) and grade (gr) ≥ 3 (BM, 38%; No BM, 39%). Groups were also comparable with respect to immune effector cell-associated neurotoxicity syndrome (ICANS) and associated neurologic events (any-grade, 6% vs 9%; gr ≥ 3, 4% vs 4%) and neutropenia (any-grade, 10% vs 15%; gr ≥ 3, 8% vs 8%). AEs numerically different in the BM vs No BM group included gr ≥ 4 TRAEs (17%, 7%) and any-grade CRS (67%, 54%). The only grade 5 TRAE (pneumonitis) occurred in the BM group. Conclusions: Tarlatamab continues to show promising efficacy and is generally safe in pts with ES SCLC irrespective of the presence of BM. Rates of ICANS and associated neurologic AEs were comparable between those with and without BM at baseline. Reference: 1. Paz-Ares L, et al. J Clin Oncol. DOI:10.1200/JCO.22.02823. Clinical trial information: NCT03319940 . [Table: see text]

Efficacy and safety of nanopaclitaxel formulation for cancer treatment: evidence from randomized clinical trials.

Aim: We aimed to analyze efficacy and adverse events for nano-bound paclitaxel in cancer treatment, which remain controversial. Method: We obtained relevant previously published studies and extracted data on the efficacy and adverse events of nano-bound paclitaxel. Fifteen randomized clinical trials were included. Results: Nanoparticle albumin-bound (Nab-) paclitaxel was beneficial in terms of objective response rate (odds ratio [OR]: 1.08, 95% CI: 0.72-1.62) and partial response (OR: 1.28, 95% CI: 0.89-1.83), while polymeric micellar (PM-) paclitaxel was beneficial in terms of objective response rate (OR: 1.76) and partial disease (hazard ratio [HR]: 0.65). Both Nab-paclitaxel and PM-paclitaxel resulted in slightly longer overall survival (HR: 0.93 and 0.94) and progression-free survival (HR: 0.93 and 0.87) when compared with solvent-based paclitaxel. Peripheral sensory neuropathy (OR: 3.47), neutropenia (OR: 1.79) and anemia (OR: 1.79) were more frequent after Nab-paclitaxel treatment. Conclusion: Nanopaclitaxel formulations have a better efficacy in cancer treatment; however, they increase the risk of hematological adverse events and peripheral sensory neuropathy. The PM-paclitaxel treatment had a high safety effect.

A novel therapeutic strategy of combined camrelizumab and apatinib for the treatment of advanced hepatocellular carcinoma.

83 patients with hepatocellular carcinoma (HCC) admitted to the interventional oncology department were randomly divided into two groups. Apatinib and camrelizumab were administered to 42 patients in group A, whereas sorafenib was administered to 41 patients in group B for three months. The clinical efficacy was evaluated in terms of objective response rate (ORR), and disease control rate (DCR). Certain tumor markers like alpha-fetoprotein (AFP), carbohydrate antigen 199 (CA199), carcinoembryonic antigen (CEA), hypoxia-inducible factor (HIF-1), immune function T lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+) were determined before and after treatment. The serum levels of vascular endothelial growth factor (VEGF), osteopontin (OPN), aspartate aminotransferase (AST), and epidermal growth factor 7 (EGF7)] were observed. The survival time between the two groups was compared, such as progression-free survival (PFS) and median survival (MS). Finally, the toxicity and side effects data were also obtained. The ORR and DCR of group A were 69.05% and 88.10%, respectively, which were significantly higher (P<0.05) than group B (ORR=53.66% and DCR=70.73%). After treatment, the AFP, CA199, CEA, and HIF-1 levels of both groups decreased significantly (P<0.05), and the respective biomarker levels of group A were lower than those of group B (P<0.05). Following treatment, CD3+, CD4+, CD4+/CD8+ index in group A significantly increased (P<0.05) while CD8+ level was significantly decreased (P<0.05). Compared to group B, a significant increase was observed in group A's CD3+, CD4+, and CD4+/CD8+ index. There were no significant changes in CD3+, CD4+, CD8+, CD4+/CD8+ indexes before and after treatment in group B (P>0.05). The serum level of VEGF, OPN, EGF-7 and AST indexes of group A&B were decreased significantly (P<0.05). Compared with group B, the VEGF, OPN, EGF7 and AST indexes of group A were significantly reduced (P<0.05). PFS and MS in group A were significantly higher than in group B (P<0.05). There was no significant difference between groups A and B in terms of toxicity and adverse effects (P>0.05). In treating HCC, combining apatinib and camrelizumab can reduce tumor markers, enhance the immune system and curative effect, and prolong patient survival. The underline mechanism is related to the down-regulation of VEGF, OPN and HIF-1 indexes.

A prospective phase II trial of pembrolizumab plus lenvatinib in advanced adrenal cortical carcinoma after failure of platinum- and mitotane-based chemotherapy (ACCOMPLISH).

TPS3 Background: Adrenal cortical carcinoma (ACC) is a very rare cancer with poor prognosis. For advanced ACC, systemic treatment options are limited. There has been only one randomized phase III clinical trial in which etoposide, doxorubicin, cisplatin, and mitotane (EDP-M) achieved statistically significant improvement in terms of objective response rate (ORR) and progression-free survival (PFS). However, after failure of EDP-M regimen, no universally accepted treatment option exists. In human ACC sample, vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) expression were higher than adrenal adenoma, and 10-20% of tumor cells and 70% of tumor infiltrating monocyte are PD-L1 positive. In retrospective review of cabozantinib in advanced ACC, cabozantinib demonstrated 19% of ORR and 16.2 weeks of median PFS. Also, in phase II clinical trial of pembrolizumab in advanced ACC, ORR of 14-23% were shown. Considering synergism of VEGFR tyrosine kinase inhibitors (TKIs) and immune check point inhibitors (ICIs) in other cancers, combination of VEGFR TKI and ICI is an attractive approach in advanced ACC. Methods: This is an open-label,single-arm,multi-center,investigator-initiated phase II trial of lenvatinib plus pembrolizumab in patients with advanced ACC who failed previous platinum and mitotane therapy (NCT 05036434). Using Simon’s optimal two-stage design, 10 patients will be enrolled initially in the first stage. If at least 2 or more patients achieve complete response or partial response, the trial will continue until enrollment of a total of 30 patients. Patients will receive 200 mg of pembrolizumab every 3 weeks intravenously and 20 mg of daily lenvatinib orally until disease progression, intolerable toxicity, or patients’ withdrawal of consent. Key eligibility criteria are age ≥ 19 years, ECOG PS 0-1, biopsy-proven ACC, disease progression despite cisplatin- and mitotane-based chemotherapy, measurable disease according to RECIST v1.1, no uncontrolled hypertension, adequate kidney, liver, and bone marrow function. Primary endpoint is ORR, and secondary endpoints include PFS, safety profile, overall survival, duration of response. Exploratory evaluation of tumor genomics and immune microenvironment by whole exome sequencing, single-cell RNA sequencing, and T cell receptor sequencing in correlation with response will be performed. Enrollment began in June 2022 and projected enrollment goal is 3 years. Clinical trial information: NCT05036434 .

Efficacy of Transarterial Chemoembolization Combined with Tyrosine Kinase Inhibitors for Hepatocellular Carcinoma Patients with Portal Vein Tumor Thrombus: A Systematic Review and Meta-Analysis.

Background: Transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) may enhance the efficacy of treatment for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT); however, it remains unclear. We aim to evaluate the efficacy of TACE combined with TKIs. Methods: A thorough literature search was performed on major databases since their inception until October 2022. Based on the eligibility criteria, eight studies (2103 patients) were included. Results: Meta-analysis showed that TACE+sorafenib/apatinib had a better tumor response (objective response rate (ORR): RR = 4.85, 95% CI 2.68−8.75, disease control rate (DCR): RR = 3.23, 95% CI 1.88−5.56), and prolonged OS (HR = 0.50, 95%CI 0.42−0.60, p < 0.00001) than TACE alone. TACE+lenvatinib was stronger than TACE+sorafenib in ORR (60.7% vs. 38.9%) and TTP (HR = 0.61, 95% CI 0.43−0.86), whereas it was similar in DCR (96.4% vs. 96.3%) and OS (HR = 0.70 95% CI 0.46−1.05). Conclusions: TACE plus sorafenib or apatinib was superior to TACE alone for hepatocellular carcinoma with PVTT; no significant advantage was found between TACE+lenvatinib and TACE+sorafenib, although TACE+lenvatinib performed better in terms of ORR and TTP.

Atezolizumab plus bevacizumab versus lenvatinib as first-line therapy for advanced hepatocellular carcinoma: A systematic review and meta-analysis.

Studies comparing atezolizumab plus bevacizumab (ATE/BEV) vs. lenvatinib (LEN) for advanced hepatocellular carcinoma (aHCC) have shown conflicting results. With this background, we aimed to collate the available evidence comparing ATE/BEV and LEN in aHCC. A comprehensive search of three databases was conducted from inception to November 2022 for studies comparing ATE/BEV with LEN for managing aHCC. Results were presented with their 95% confidence intervals (95% CI) as the hazard ratio (HR) for time-to-event outcomes or odds ratios (OR) for dichotomous outcomes. A total of 8 studies were included. On analysis of matched cohorts, there was no difference in the objective response rate (ORR) (adjusted odds ratio [aOR] = 1.15, 95% CI: 0.83-1.61) or disease control rate (DCR) (aOR = 0.83, 95% CI: 0.49-1.38) between groups. Three studies reported a significantly longer progression-free survival (PFS) with ATE/LEN, while one reported a longer PFS with LEN. The adjusted hazard ratio (aHR) for PFS available from three studies was comparable (HR = 1.06, 95% CI: 0.75-1.50). Data were insufficient to carry out a formal analysis for overall survival (OS), but none of the studies reported any difference in OS. On comparison of overall adverse events (AE) and ≥ grade 3 AE, there was no difference in the overall analysis, but higher risk of AE with LEN on sensitivity analysis. Based on the currently available literature, LEN was found to be non-inferior to ATE/BEV in terms of ORR, DCR, and PFS. However, LEN may be associated with a higher incidence of AEs. Further head-to-head trials are required to demonstrate the superiority of ATE/BEV over LEN.

Analysis on Efficacy of Hepatic Artery Infusion Chemotherapy with or without Lenvatinib for Unresectable Hepatocellular Carcinoma

Introduction: For patients with advanced hepatocellular carcinoma (HCC), hepatic artery infusion chemotherapy (HAIC) is a common and mature treatment, but the safety and efficacy of HAIC combined with lenvatinib for advanced HCC patient treatment remains unclear. Therefore, this study compared the safety and efficacy of HAIC with or without lenvatinib in unresectable HCC patients. Methods: We retrospectively analyzed 13 unresectable advanced HCC patients who received HAIC monotherapy or combination therapy of HAIC and lenvatinib. Overall survival (OS), disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), incidence of adverse events (AEs), and changes in liver function were compared between the two groups. We applied a Cox regression analysis to evaluate the independent risk factors affecting survival outcomes. Results: The ORR in the HAIC+lenvatinib group was markedly increased compared to the HAIC group (p < 0.05), while the DCR in the HAIC group was higher (p > 0.05). No notable difference was found between the two groups in median OS and PFS (p > 0.05). Compared to the HAIC+lenvatinib group, more patients had improved liver function in the HAIC group after treatment, but the difference was not dramatical (p > 0.05). The AEs incidence was 100.00% in both groups, which was relieved with corresponding treatment. Besides, Cox regression analysis did not identify independent risk factors related to OS and PFS. Conclusion: Combination therapy of HAIC and lenvatinib notably performed better than the HAIC monotherapy in patients with unresectable HCC in terms of ORR and was well tolerated, which deserves further investigation with large-scale clinical trials.

Pembrolizumab versus paclitaxel for previously treated, advanced gastro-esophageal junction cancer: A systematic review and meta-analysis of randomized clinical trials

This paper aims to compare the effectiveness and safety of pembrolizumab and paclitaxel as a second line for patients with locally advanced gastroesophageal cancer. By searching PubMed, Scopus, Web of Science, and Ovid, any randomized clinical study comparing the effectiveness of paclitaxel and pembrolizumab as second-line therapy for advanced gastroesophageal cancer met the inclusion criteria. Only 3 of the 23 eligible studies that were fully reviewed were eligible for meta-analysis. The total number of patients included in the meta-analysis was 635 in the pembrolizumab group and 596 in the paclitaxel group. In terms of objective response rate, there was no statistically significant difference between pembrolizumab and paclitaxel (relative risk = 1.10, 95% CI = 0.80-1.50, P = .57). Furthermore, Pembrolizumab and paclitaxel did not differ in terms of the rate of partial response statistically significantly from one another, according to the overall analysis (relative risk = 0.93, 95% CI = 0.57-1.52, P-value = .78). There is no difference between pembrolizumab and paclitaxel in objective response rate. The objective response rate shows that doctors may consider either treatment for patients with advanced gastroesophageal cancer, given the time to response is comparable across therapies.

CT-guided Radioactive 125I Seed Implantation for Abdominal Incision Metastases of Colorectal Cancer: Safety and Efficacy in 17 Patients

IntroductionTo retrospectively evaluate the safety and efficacy of computed tomography (CT)-guided iodine-125 (125I) seed implantation for patients with abdominal incision metastases from colorectal cancer. Materials and MethodsData of patients with abdominal incision metastases of colorectal cancer from November 2010 to October 2020 were retrospectively reviewed. Each incisional metastasis was percutaneously treated with 125I seed implantation under CT guidance. Follow-up contrast-enhanced CT was reviewed, and the outcomes were evaluated in terms of objective response rate, complications, and overall survival. ResultsA total of 17 patients were enrolled in this study. The median follow-up was 18 months (range, 2.7-22.1 months). At 3, 6, 12, and 18 months after the treatment, objective response rate was 52.9%, 63.6%, 33.3%, and 0%, respectively. A small amount of local hematoma occurred in two patients and resolved spontaneously without any treatment. Two patients experienced a minor displacement of radioactive seeds with no related symptoms. Severe complications, such as massive bleeding and radiation injury, were not observed. No ≥ grade 3 adverse events were identified. By the end of follow-up, 14 patients died of multiple hematogenous metastases. The one-year overall survival rate was 41.6%, and the median overall survival was 8.6 months. ConclusionCT-guided 125I seed implantation brachytherapy is safe and feasible for patients with abdominal incision metastases from colorectal cancer.

Pretreatment platelet-to-lymphocyte ratio (PLR) as a prognosticating indicator for gastric cancer patients receiving immunotherapy

BackgroundPrevious investigations suggest that systemic inflammation markers are able to provide prognostic value in several cancers. This study seeks to characterize the ability of pretreatment platelet-to-lymphocyte ratio (PLR) to prognosticate advanced or metastatic gastric cancer patients (AGC or MGC, respectively) receiving immunotherapy.MethodsAGC and MGC patients exposed to PD-1 inhibitors from January 2016–August 2021 in the Chinese PLA General Hospital were recruited. Correlations between PLR and overall survival (OS), progression-free survival (PFS), and immunotherapy-associated tumor response rates were determined.Results237 patients were enrolled for this retrospective investigation. The 6 month and 12 month PFS based on the area under the curve value was 0.60 and 0.65 (p < 0.05). based on a calculated PLR cut-off value of 139.41, The PLR < 139.41 group has a longer OS in contrast with the PLR ≥ 139.41 group (13.46 m vs 10.71 m, HR = 0.57, 95% CI 0.42–0.78, p = 0.004). The PLR < 139.41 group had a PFS of 7.93 m in contrast to the 4.75 m seen in those with PLR ≥ 139.41 group (HR = 0.57, 95% CI 0.43–0.76, p = 0.002). The disease control rate (DCR) and objective response rate (ORR) were 86.17% and 30.85%, respectively, in the PLR < 139.41 group, but were 82.52% and 32.17%, respectively in the PLR ≥ 139.41 group. Both groups did not show any marked differences in terms of ORR and DCR (p = 0.887, p = 0.476). PLR is an independent prognostic indicator for OS and PFS upon uni- and multivariate analyses (p < 0.05).ConclusionsPre-treatment PLR correlated significantly with PFS and OS in AGC and MGC patients who received immunotherapy. An elevated PLR may provide guidance on subsequent treatment options.