A global phase 3 study of serplulimab plus chemotherapy as first-line treatment for advanced squamous non-small-cell lung cancer (ASTRUM-004).

Combining immunotherapy with chemotherapy can provide improved survival in advanced squamous non-small-cell lung cancer (NSCLC) patients without targetable gene alterations. 537 previously untreated patients with stage IIIB/IIIC or IV squamous NSCLC without targetable gene alterations were enrolled and randomized (2:1) to receive serplulimab 4.5 mg/kg or placebo, both in combination with nab-paclitaxel and carboplatin, intravenously in 3-week cycles. The primary endpoint of progression-free survival (PFS) was met at the first interim analysis. At the second interim analysis, PFS benefit was maintained in serplulimab-chemotherapy group (hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.42-0.67). At the final analysis, serplulimab-chemotherapy significantly improved median OS compared to placebo-chemotherapy (HR 0.73, 95% CI 0.58-0.93; p = 0.010). Grade ≥3 serplulimab or placebo-related adverse events occurred in 126 (35.2%) and 58 (32.4%) patients, respectively. Our results demonstrate that adding serplulimab to chemotherapy significantly improves survival in advanced squamous NSCLC patients, with manageable safety.

Circular RNA circ_0020123 Promotes Non-Small Cell Lung Cancer Progression Through miR-384/TRIM44 Axis.

BACKGROUND: It was reported that circular RNAs (circRNAs) and microRNAs (miRNAs) were related to non-small cell lung cancer (NSCLC) development. However, the detailed mechanisms of circ_0020123 and miR-384 in NSCLC are elusive. METHODS: QRT-PCR and Western blot assay were performed to detect the transcription and protein levels of genes, respectively. Then, the functional experiments, including MTT assay, flow cytometry, and transwell assay, were employed. Besides, the interaction between miR-384 and circ_0020123 or tripartite motif­containing protein 44 (TRIM44) was predicted by starbase or targetscan, and then verified by the dual-luciferase reporter, RNA pull-down assays and RNA immunoprecipitation assay (RIP). Mouse xenograft assay was performed to evaluate the effect of circ_0020123 on tumor growth in vivo. RESULTS: Levels of circ_0020123 and TRIM44 were enhanced, and the miR-384 level was attenuated in NSCLC tissues and cells. Circ_0020123 depletion attenuated the abilities of NSCLC cell viability, migration, invasion, and epithelial-mesenchymal transition (EMT), and induced apoptosis. Besides, circ_0020123 interacted with miR-384, and miR-384 targeted TRIM44. Circ_0020123 regulated cell progression by regulating miR-384 and subsequently mediated TRIM44 expression. Besides, circ_0020123 depletion repressed tumor growth in vivo. CONCLUSION: We demonstrated that circ_0020123 knockdown suppressed NSCLC cell progression by regulating the miR-384/TRIM44 axis, providing the theoretical basis for the therapy of NSCLC.

Biosimilar candidate IBI305 plus paclitaxel/carboplatin for the treatment of non-squamous non-small cell lung cancer.

BACKGROUND: Bevacizumab is a monoclonal antibody (mAb) against vascular endothelial growth factor (VEGF) and used for treatments of various cancers. Due to the high costs of bevacizumab treatments, a biosimilar provides an affordable alternative therapy for cancer patients. METHODS: In this randomized, double-blind, multicenter, phase 3 study, locally advanced, metastatic or recurrent non-squamous non-small cell lung cancer (NSCLC) patients with wild-type epidermal growth factor receptor were enrolled and randomized (1:1) into IBI305 or bevacizumab groups. Patients received 6 cycles of paclitaxel/carboplatin plus IBI305 or bevacizumab 15 mg/kg intravenously followed by IBI305 or bevacizumab 7.5 mg/kg maintenance until disease progression, unacceptable toxicity or death. The primary endpoint was confirmed objective response rate (ORR) by an independent radiological review committee (IRRC) and secondary endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response (DOR), overall survival (OS) and safety. RESULTS: A total of 450 NSCLC patients were enrolled (224 in IBI305 group and 226 in bevacizumab group). ORRs were 44.3% for IBI305 and 46.4% for bevacizumab, and the ORR ratio was 0.95 (90% CI: 0.803 to 1.135), within the predefined equivalence margin of 0.75 to 1.33. No significant difference in PFS (7.64 vs. 7.77 m, P=0.9987) was observed between the 2 groups. Serious adverse events (AEs) occurred in 33.5% (75/224) of patients in the IBI305 group and 37.6% (85/226) in the bevacizumab group. AEs ≥ grade 3 were similar in the IBI305 and bevacizumab groups [84.4% (189/224) vs. 89.8% (203/226), P=0.085]. CONCLUSIONS: IBI305 is similar to bevacizumab in terms of efficacy and safety. TRIAL REGISTRATION: Clinicaltrials.org Identifier: NCT02954172. Registered on 3 November 2016. Https://clinicaltrials.gov/.

Excision repair cross-complementing group 1 (ERCC1) overexpression inhibits cell apoptosis and is associated with unfavorable prognosis of esophageal squamous cell carcinoma.

Excision repair cross-complementing group 1 (ERCC1) functions as a nucleotide excision repair (NER) enzyme. Altered ERCC1 expression or function is closely associated with cancer development and progression. This study determined the association of ERCC1 expression with survivin expression, clinicopathological characteristics, and survival of esophageal squamous cell carcinoma (ESCC) patients after postoperative concurrent chemoradiotherapy.Tissue specimens from 102 resected ESCC patients were acquired for immunohistochemical analysis of ERCC1 and survivin protein expression.ERCC1 expression was detected in 62.7% of ESCC tissues and in 9.8% of normal squamous epithelium tissues (P < .01), while survivin expression was detected in 60.8% of ESCC tissues and in 19.6% of normal squamous epithelia (P < .01). ERCC1 overexpression associated with advanced tumor clinical stage and lymph node metastasis (P < .05), but not with tumor size, depth of invasion, or differentiation (P > .05). ERCC1 overexpression was also associated with survivin levels (r = 0.42, P < .01) and worse progression-free survival of ESCC patients after concurrent chemoradiotherapy. Multivariate analysis data revealed that ERCC1 and survivin protein expression were independent predictors of overall survival of ESCC patients after chemotherapy and/or radiotherapy (P < .05).ERCC1 overexpression is an important phenotype that is associated with ESCC lymph node metastasis and advanced tumor clinical stages. ERCC1 expression may also inhibit ESCC cell apoptosis via regulating survivin expression, and ERCC1 and survivin overexpression are independent predictors of prognosis for ESCC patients who receive chemotherapy and/or radiotherapy.

Sirtuin 2 (Sirt2) Expression Predicts Lymph Node Metastasis and Poor Overall Survival of Patients with Esophageal Squamous Cell Carcinoma.

BACKGROUND: Altered expression of Sirtuin 2 (Sirt2) was associated with cancer development and progression. This study further assessed the association of Sirt2 expression with clinicopathological data and prognosis of patients with esophageal squamous cell carcinoma (ESCC) after postoperative concurrent chemoradiotherapy. METHODS: Tissue specimens from 95 ESCC patients were collected for immunohistochemical analysis of Sirt2 expression, which was used to determine association with patient clinicopathological and survival data. RESULTS: Sirt2 protein was expressed in 53.7% of ESCC tissue specimens but only in 25.3% of normal squamous epithelium (p = 0.000). Sirt2 expression was associated with tumor invasion (p = 0.005), lymph node metastasis (p = 0.003), and advanced clinical stage (p = 0.000), but not with tumor size (p = 0.199), or differentiation (p = 0.177). Sirt2 expression was associated with poor overall and progression-free survival (p = 0.034). The multivariate analysis showed that Sirt2 expression was an independent predictor for overall survival of patients with resected ESCC followed by concurrent chemoradiotherapy (p = 0.048). CONCLUSIONS: Sirt2 protein expression in ESCC tissue specimens was associated with ESCC invasion, lymph node metastasis, and advanced tumor clinical stage, as well as poor overall and poor progression-free survival. Sirt2 expression is an independent prognostic predictor for ESCC patients.