Efficacy and safety of camrelizumab combined with chemotherapy in the first-line treatment of advanced gastric cancer: a single-arm, phase II study.

Background: Chemotherapy with SOX (S-1 and oxaliplatin) regimen showed good efficacy and a favorable safety profile in advanced gastric cancer. Anti-programmed cell death protein 1 (PD-1) antibody camrelizumab also demonstrated antitumor activity in this setting in a phase I study. However, the efficacy and safety of camrelizumab plus SOX for advanced gastric cancer have not been investigated. Thus, this study aimed to address this objective. Methods: This phase II study evaluated the efficacy and safety of camrelizumab plus SOX in previously untreated advanced gastric cancer. Patients received camrelizumab (200 mg intravenously every 3 weeks) plus SOX (S-1, 40 mg/m2 orally twice daily on days 1-14; oxaliplatin, 130 mg/m2 intravenously on day 1 every 3 weeks) until disease progression, death, or intolerable toxicity. Camrelizumab was prescribed for up to a year. The primary endpoint was progression-free survival (PFS). The second endpoints were overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Results: A total of 25 patients were enrolled and received at least 1 dose of study drug. The median PFS was 7.4 months [95% confidence interval (CI): 5.6-16.4]. The median OS was 20.2 months (95% CI: 10.5-29.9); ORR was 36% (95% CI: 18.0-57.5%); DCR was 92% (95% CI: 74.0-99.0%). Among the 25 patients, 22 (88%) experienced any-grade adverse events (AEs), and 7 (28%) patients experienced grade ≥3 AEs. Conclusions: Camrelizumab plus SOX showed promising efficacy and an acceptable safety profile as the first-line treatment for advanced gastric cancer.

CMTM4 inhibits gastric tumorigenesis and metastasis.

Background: CKLF-like MARVEL transmembrane domain-containing 4 (CMTM4) is involved in immune regulation and tumor progression; however, its role in gastric cancer (GC) remains unclear. This study explored the role and mechanism of CMTM4 in GC. Methods: Immunohistochemistry was used to analyze CMTM4 expression in human gastric biopsied cells from patients with GC (N=23) or chronic superficial gastritis (N=23). To investigate the function of CMTM4 in GC cells, the gene CMTM4 was knocked down and overexpressed in human gastric adenocarcinoma cell line AGS. The gene CMTM4 was overexpressed in AGS cells and human gastric cell line SGC7901. Cell Counting Kit 8 (CCK-8) and cell clonogenic assays were used to analyze the proliferation of the GC cells. Flow cytometry was used to analyze the effects of CMTM4 on apoptosis and the cell cycle. Wound healing and transwell assays were used to analyze the migration and invasion of the gastric cells, respectively. The mechanism of CMTM4 in GC cells was explored using the tandem mass tags (TMTs) proteome and verified by western blot analysis. Results: CMTM4 expression was more downregulated in the human GC tissues than the gastritis tissues. CMTM4 overexpression significantly inhibited the proliferation, migration, and invasion of the GC cells, whereas CMTM4 knockdown enhanced gastric cell proliferation (P>0.05), migration (P>0.05), and invasion (P>0.05). Flow cytometry showed that CMTM4 promoted apoptosis and resulted in G1/S arrest in the GC cells. In addition, the proteome and western blot results showed that STAT1 was significantly upregulated, and the STAT1 signaling pathways were enriched in the GC cells overexpressing CMTM4. Conclusions: Our results suggest that CMTM4 plays a tumor-suppressive role in GC and may affect the growth, migration, and invasion of GC cells through the STAT1 signaling pathway. CMTM4 might have potential value as a prognosis marker and potential therapeutic target for GC therapy.

Next-generation sequencing impact on cancer care: applications, challenges, and future directions.

Fundamentally precision oncology illustrates the path in which molecular profiling of tumors can illuminate their biological behavior, diversity, and likely outcomes by identifying distinct genetic mutations, protein levels, and other biomarkers that underpin cancer progression. Next-generation sequencing became an indispensable diagnostic tool for diagnosis and treatment guidance in current clinical practice. Nowadays, tissue analysis benefits from further support through methods like comprehensive genomic profiling and liquid biopsies. However, precision medicine in the field of oncology presents specific hurdles, such as the cost-benefit balance and widespread accessibility, particularly in countries with low- and middle-income. A key issue is how to effectively extend next-generation sequencing to all cancer patients, thus empowering treatment decision-making. Concerns also extend to the quality and preservation of tissue samples, as well as the evaluation of health technologies. Moreover, as technology advances, novel next-generation sequencing assessments are being developed, including the study of Fragmentomics. Therefore, our objective was to delineate the primary uses of next-generation sequencing, discussing its' applications, limitations, and prospective paths forward in Oncology.

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as biomarkers to prognosticate survival in advanced gastric cancer patients in the era of immunotherapy: a systematic review and meta-analysis.

Background: Gastric cancer (GC) remains an important global health concern with limited treatment options for advanced cases. Immunotherapy has shown promising results, but identifying predictive biomarkers for treatment efficacy is challenging. Novel inflammatory markers, such as the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR), derived from complete blood count measurements, have gained attention as potential prognostic indicators. This systematic review and meta-analysis investigates the roles of the PLR and NLR as predictors of overall survival (OS) and progression-free survival (PFS) in advanced GC and gastroesophageal junction cancer (GEJC) patients treated with immunotherapy. Methods: A comprehensive search of the literature was conducted through PubMed, Embase, and Cochrane Library to identify relevant studies. A total of 16 studies involving NLR and 8 studies involving PLR were included. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess the association between high biomarker values and poor OS and PFS. Subgroup analyses were performed to explore potential sources of heterogeneity. Poor OS, PFS were defined by each study as statistically significant shorter survival. Results: A high NLR was significantly associated with worse OS (HR: 2.11; 95% CI: 1.70-2.62) and PFS (HR: 1.76; 95% CI: 1.43-2.17). High PLR was also significantly associated with poorer OS (HR: 1.77; 95% CI: 1.44-2.17) and PFS (HR: 1.61; 95% CI: 1.33-1.96). Subgroup analyses and sensitivity analyses supported the robustness of these findings. Publication bias was noted in NLR analysis for OS but not for PFS. PLR analysis showed low publication bias. Conclusions: Elevated NLR and PLR are associated with unfavorable OS and PFS outcomes in advanced GC/GEJC patients on immunotherapy. These findings imply the utility of these easily accessible biomarkers in prognostic assessment. However, standardized cutoff values and further research on interactions with the tumor microenvironment and comorbidities are needed. Additional prospective studies are warranted to validate these findings for both biomarkers.

Challenges and opportunities in building a health economic framework for personalized medicine in oncology.

Personalized medicine has allowed for knowledge at an individual level for several diseases and this has led to improvements in prevention and treatment of various types of neoplasms. Despite the greater availability of tests, the costs of genomic testing and targeted therapies are still high for most patients, especially in low- and middle-income countries. Although value frameworks and health technology assessment are fundamental to allow decision-making by policymakers, there are several concerns in terms of personalized medicine pharmacoeconomics. A global effort may improve these tools in order to allow access to personalized medicine for an increasing number of patients with cancer.

Evidence Strength of Pharmaceutical Industry-Funded Clinical Trials in Metastatic NSCLC: A Comparison With Other Sources of Funding.

INTRODUCTION: Clinical trials are expensive and often require funding from the pharmaceutical industry (PI). We aimed to compare studies funded by the PI with those funded by other sources in terms of costs, reported results, and strength of evidence. METHODS: We searched PubMed for clinical trial reports on metastatic NSCLC published between 2012 and 2017. We divided all the studies into two groups: studies funded by the PI and those funded by other sources. The primary end point was to compare the evidence strength of each group. The secondary end points were to compare the number of patients included, the number and costs of innovative drugs studied, whether there was preferential reporting of positive results in the experimental arm, and the risk of bias. RESULTS: We found 3004 studies, and of these, we analyzed 477 studies (275 sponsored by the PI and 202 funded by other sources). A total of 85,328 patients overall were included (64,434 in studies sponsored by the PI and 20,894 in studies with other funding sources; p < 0.001). The studies funded by the PI had stronger evidence (p < 0.001), evaluated more innovative therapies (72% versus 36%; p < 0.001), and resulted in a higher proportion of open-access manuscripts (63% versus 47%; p < 0.001). There was no considerable difference regarding the reporting of experimental arm superiority or the risk of bias between the two groups. CONCLUSIONS: Compared with studies from other sources of funding, those funded by the PI in the lung cancer field collected stronger evidence, assessed more expensive and innovative therapies, and seemed to equally emphasize positive and negative results.