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Background Lipusu is the first commercialized liposomal formulation of paclitaxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma (LSCC) in a small‐scale study. Here, we conducted a multicenter, randomized, phase 3 study to compare the efficacy and safety of cisplatin plus Lipusu (LP) versus cisplatin plus gemcitabine (GP) as first‐line treatment in locally advanced or metastatic LSCC. Methods Patients enrolled were aged between 18 to 75 years, had locally advanced (clinical stage IIIB, ineligible for concurrent chemoradiation or surgery) or metastatic (Stage IV) LSCC, had no previous systemic chemotherapy and at least one measurable lesion as per the Response Evaluation Criteria in Solid Tumors (version 1.1) before administration of the trial drug. The primary endpoint was progression‐free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety profiles. To explore the possible predictive value of plasma cytokines for LP treatment, plasma samples were collected from the LP group at baseline and first efficacy evaluation time and were then subjected to analysis by 45‐Plex ProcartaPlex Panel 1 to detect the presence of 45 cytokines using the Luminex xMAP technology. The correlation between treatment outcomes and dynamic changes in the levels of cytokines were evaluated in preliminary analyses. Results The median duration of follow‐up was 15.4 months. 237 patients in the LP group and 253 patients in the GP group were included in the per protocol set (PPS). In the PPS, the median PFS was 5.2 months versus 5.5 months in the LP and GP group (hazard ratio [HR]: 1.03, P = 0.742) respectively. The median OS was 14.6 months versus 12.5 months in the LP and GP group (HR: 0.83, P = 0.215). The ORR (41.8% versus 45.9%, P = 0.412) and DCR (90.3% versus 88.1%, P = 0.443) were also similar between the LP and GP group. A significantly lower proportion of patients in the LP group experienced adverse events (AEs) leading to treatment interruptions (10.9% versus 26.4%, P < 0.001) or treatment termination (14.3% versus 23.1%, P = 0.011). The analysis of cytokine levels in the LP group showed that low baseline levels of 27 cytokines were associated with an increased ORR, and 15 cytokines were associated with improved PFS, with 14 cytokines, including TNF‐α, IFN‐γ, IL‐6, and IL‐8, demonstrating an overlapping trend. Conclusion The LP regimen demonstrated similar PFS, OS, ORR and DCR as the GP regimen for patients with locally advanced or metastatic LSCC but had more favorable toxicity profiles. The study also identified a spectrum of different cytokines that could be potentially associated with the clinical benefit in patients who received the LP regimen., Cisplatin plus Lipusu (LP) regimen has comparable efficacy and more favorable toxicity profiles compared with cisplatin plus gemcitabine (GP) regimen for patients with advanced LSCC. The study also demonstrated that LP had a significant impact on the levels of plasma cytokines and a spectrum of cytokines were associated with clinical benefit in patients who received LP. Thus, our results provided a new option for patients with advanced LSCC.

Background Previous studies have demonstrated the preclinical pharmacological and toxicological consistency, and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab (Avastin). This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first‐line treatment of Chinese patients with advanced or recurrent non‐squamous non‐small cell lung cancer (NSCLC). Methods Stage IIIB‐IV NSCLC patients with evaluable lesions, good physical status, and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin (combined treatment) for 4‐6 cycles, followed by maintenance monotherapy with LY01008 until disease progression, intolerable toxicity, or death. The primary endpoint was objective response rate (ORR) in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 confirmed by independent radiological review committees (IRRC). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression‐free survival (PFS), overall survival (OS), and safety. This study was registered in ClinicalTrials.gov (NCT03533127). Results Between December 15th, 2017, and May 15th, 2019, a total of 649 patients were randomized to the LY01008 (n = 324) or Avastin (n = 325) group. As of September 25th, 2019 for primary endpoint analysis, 589 patients received ORR evaluation, with a median number of combined treatment cycles of 5 (range 1‐6) and median duration of treatment of 3.0 (range 0.0‐5.1) months. ORR of response‐evaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%, respectively. The stratified ORR ratio was 0.91 (90% CI 0.80‐1.04, within the prespecified equivalence margin of 0.75‐1.33). Up to May 15th, 2020, with a median follow‐up of 13.6 (range 0.8‐28.4) months, no notable differences in DCR, median DoR, median PFS, median OS, and 1‐year OS rate were observed between the LY01008 and Avastin groups. There were no clinically meaningful differences in safety and immunogenicity across treatment groups. Conclusions LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non‐squamous NSCLC. LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable, metastatic, or recurrent non‐squamous NSCLC patients in the first‐line setting., This study demonstrated similarity between LY01008 and reference bevacizumab (Avastin) in terms of efficacy, safety, and immunogenicity in combination with paclitaxel and carboplatin as first‐line treatment in Chinese patients with advanced non‐squamous NSCLC.

Rationale: Platinum-based chemotherapy is one of treatment mainstay for patients with advanced lung squamous cell carcinoma (LUSC) but it is still a "one-size fits all" approach. Here, we aimed to investigate the predictive and monitoring role of circulating cell-free DNA (cfDNA) profiling for the outcome of first-line chemotherapy in patients with advanced LUSC. Methods: Peripheral blood samples of 155 patients from a phase IV trial and 42 cases from an external real-world cohort were prospectively collected. We generated a copy number variations-based classifier via machine learning algorithm to integrate molecular profiling of cfDNA, named RESPONSE SCORE (RS) to predict the treatment outcome. To monitor the treatment efficacy, cfDNA samples collected at different time points were subjected to an ultra-deep sequencing platform. Results: The results showed that patients with high RS showed substantially higher objective response rate than those with low RS in training set (P < 0.001), validation set (P < 0.001) and real-world cohort (P = 0.019). Furthermore, a significant difference was observed in both progression-free survival (training set, P < 0.001; validation set: P < 0.001; real-world cohort: P = 0.019) and overall survival (training set, P < 0.001; validation set: P = 0.037) between high and low RS group. Notably, variant allele frequency (VAF) calculated from an ultra-deep sequencing platform significantly reduced in patients experienced a complete or partial response after 2 cycles of chemotherapy (P < 0.001), while it significantly increased in these of non-responder (P < 0.001). Moreover, VAF undetectable after 2 cycles of chemotherapy was correlated with markedly better objective response rate (P < 0.001) and progression-free survival (P < 0.001) than those with detectable VAF. Conclusions: These findings indicated that the RS, a circulating cfDNA sequencing-based stratification index, could help to guide first-line chemotherapy in advanced LUSC. The change of VAF is valuable to monitor the treatment response.

sBackgroundCancer patients are considered to be highly susceptible to viral infections, however, the comprehensive features of COVID-19 in these patients remained largely unknown. The present study aimed to assess the clinical characteristics and outcomes of COVID-19 in a large cohort of cancer patients.Design, Setting, and ParticipantsData of consecutive cancer patients admitted to 33 designated hospitals for COVID-19 in Hubei province, China from December 17, 2019 to March 18, 2020 were retrospectively collected. The follow-up cutoff date was April 02, 2020. The clinical course and survival status of the cancer patients with COVID-19 were measured, and the potential risk factors of severe events and death were assessed through univariable and multivariable analyses.ResultsA total of 283 laboratory confirmed COVID-19 patients (50% male; median age, 63.0 years [IQR, 55.0 to 70.0]) with more than 20 cancer types were included. The overall mortality rate was 18% (50/283), and the median hospitalization stay for the survivors was 26 days. Amongst all, 76 (27%) were former cancer patients with curative resections for over five years without recurrence. The current cancer patients exhibited worse outcomes versus former cancer patients (overall survival, HR=2.45, 95%CI 1.10 to 5.44, log-rank p=0.02; mortality rate, 21% vs 9%). Of the 207 current cancer patients, 95 (46%) have received recent anti-tumor treatment, and the highest mortality rate was observed in the patients receiving recent chemotherapy (33%), followed by surgery (26%), other anti-tumor treatments (19%), and no anti-tumor treatment (15%). In addition, a higher mortality rate was observed in patients with lymphohematopoietic malignancies (LHM) (53%, 9/17), and all seven LHM patients with recent chemotherapy died. Multivariable analysis indicated that LHM (p=0.001) was one of the independent factors associating with critical illness or death.ConclusionsThis is the first systematic study comprehensively depicting COVID-19 in a large cancer cohort. Patients with tumors, especially LHM, may have poorer prognosis of COVID-19. Additional cares are warranted and non-emergency anti-tumor treatment should be cautiously used for these patients under the pandemic.

D-0316 in patients with advanced T790M-positive EGFR-mutant non-small cell lung cancer who progressed on prior EGFR-TKI therapy: results from a phase II study (NCT03861156) Background: Despite initial response to EGFR-TKI, most patients (pts) develop resistance with the EGFR T790M mutation detectable in ~50% of patients treated with first-/second-generation EGFR-TKIs. D-0316 is a third-generation EGFR-TKI that is selective for both EGFR-TKI sensitizing and T790M resistance mutations in pts with non-small cell lung cancer (NSCLC). We report the results of a registered, single-arm, phase II study of D-0316 in NSCLC pts with EGFR T790M who progressed on previous treatment with first-line EGFR-TKIs. Methods: In this phase II, open-label, single-arm study, eligible pts were those who had confirmed locally advanced or metastatic NSCLC, and had disease progression after first-line EGFR-TKI and with T790M mutation. Pts were initially orally given D-0316 50 mg. However, considering the benefits and risks of the pts, the dose was modified to 100 mg once daily with a 21-day lead-in at 75 mg once daily. The primary endpoint was objective response rate (ORR) based on independent review committee (IRC) according to RECIST 1.1.Results: As of October 31, 2019, 176 pts were enrolled in the 50 mg phase, in which 90 pts had partial response, achieving an ORR of 51.1% (95%CI: 43.5-58.7). Despite the immature PFS, disease progression or death occurred in 60 pts (34.1%) and the median PFS was 8.4 months (95% CI: 8.0-NE). Between September 12, 2019 and July 29, 2020, 689 pts were screened and 290 pts (median age 62.5) were enrolled in China and received 100mg D-0316 with a 21-day lead-in at 75 mg. At data cutoff (October 18, 2020), the median duration of follow-up was 5.5 months. 188 of the 290 pts achieved confirmed partial responses by IRC. The ORR was 64.8% (95% CI: 59.0-70.3) and the disease control rate (DCR) was 95.2% (95% CI: 92.0-97.3). The ORR was consistent across in most subgroups. Among 34 pts with brain metastases at baseline, 18 pts achieved confirmed partial responses and the intracranial ORR was 52.9% (95% CI: 35.1-70.2). The PFS, DoR, and OS were premature. The most common treatment-related adverse events were thrombocytopenia (57.2%), headache (27.6%), leukopenia (23.4%), anemia (22.1%) and rash (20.7%). The most common grade 3 or higher treatment-related adverse events were thrombocytopenia (11.7%). One death was due to treatment-related adverse events (interstitial lung disease). Six interstitial lung diseases (2.1%) were observed during study treatment. Conclusion: D-0316 has showed strong anti-tumor activities and tolerable toxicity in pts with EGFR T790M-positive NSCLC who have progressed after EGFR-TKI treatment. Citation Format: Shun Lu, Yiping Zhang, Guojun Zhang, Jianying Zhou, Shundong Cang, Ying Cheng, Gang Wu, Peiguo Cao, Dongqing Lv, Xiangming Jin, Hong Jian, Chengshui Chen, Guanming Jiang, Panwen Tian, Kai Wang, Hui Zhao, Gongyan Chen, Qun Chen, Cuimin Ding, Junquan Yang, Renhua Guo, Guoping Sun, Bin Wang, Liyan Jiang, Wu Zhuang, Zhe Liu, Jian Fang, Yunpeng Liu, Jian Zhang, Jun Chen, Yueyin Pan, Qitao Yu, Min Zhao, Jiuwei Cui, Dianming Li, Tienan Yi, Zhuang Yu, Yan Yang, Yan Zhang, Xiuyi Zhi, Yunchao Huang, Rong Wu, Liangan Chen, Aimin Zang, Lejie Cao, Qingshan Li, Xiaoling Li, Yong Song, Donglin Wang, Shucai Zhang. D-0316 in patients with advanced T790M-positive EGFR-mutant non-small cell lung cancer who progressed on prior EGFR-TKI therapy: results from a phase II study (NCT03861156) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT170.

Background Exosomes have significant implications in cancer progression via transferring various modulatory molecules. Long non-coding RNAs (lncRNAs) play essential biological roles in lung cancer. In this report, we unlock the functional mechanism of tumor protein P73 antisense RNA 1 (TP73-AS1) in lung cancer. Methods The expression analyses of TP73-AS1, microRNA-216a-5p (miR-216a-5p) and Cullin 4B (CUL4B) were performed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell migration and invasion were assessed using wound healing and transwell assays. Flow cytometry was applied to determine cell apoptosis. Colony formation assay was performed for cell survival to evaluate the effect on radiosensitivity. The intergenic interaction was analyzed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Western blot was used for associated protein determination. An in vivo experiment was conducted by establishing xenograft models in mice. Results TP73-AS1 was conspicuously overexpressed in lung cancer tissues and cells. Silencing TP73-AS1 restrained cell migration and invasion while it enhanced apoptosis and radiosensitivity of lung cancer. TP73-AS1 could bind to miR-216a-5p as well as miR-216a-5p and CUL4B. The function of TP73-AS1 downregulation in lung cancer was achieved by miR-216a-5p/CUL4B axis. Inhibition of TP73-AS1 also exerted an inhibitory effect on tumor growth and radioresistance in vivo potentially via regulating miR-216a-5p/CUL4B axis. Moreover, exosomes from lung cancer cells downregulated TP73-AS1 could repress tumor evolution and radioresistance. Conclusions Collectively, TP73-AS1 acted as a sponge of miR-216a-5p to regulate CUL4B in order to promote tumor progression and radioresistance in lung cancer cells with the implication of exosomes, which presents a novel mechanism of tumor action and radioresistance in lung cancer. Key points SIGNIFICANT FINDINGS OF THE STUDY: TP73-AS1 silence inhibits migration and invasion while elevates apoptosis and radiosensitivity in lung cancer cells TP73-AS1 targets miR-216a-5p and miR-216a-5p targets CUL4B WHAT THIS STUDY ADDS: Downregulation of TP73-AS1 reduces tumor growth and radioresistance in vivo via the miR-216a-5p/CUL4B axis Exosomes from si-TP73-AS1-transfected cells inhibits lung cancer progression and radioresistance.

Currently, adjunctive therapy for gastric cancer is not standardized worldwide and the most effective combination of different modalities has not been clearly determined. The aim of the present study was to retrospectively analyze the efficacy and toxicity of the combination of perioperative epirubicin, capecitabine and oxaliplatin (EOX) chemotherapy and postoperative concurrent chemoradiotherapy in the treatment of locally advanced gastric cancer. A total of 41 patients with locally advanced gastric cancer who had undergone perioperative EOX chemotherapy and surgical resection followed by chemoradiotherapy, were assessed. The perioperative EOX regimen consisted of 50 mg/m2 epirubicin and 130 mg/m2 oxaliplatin on day 1, with 625 mg/m2 capecitabine administered twice daily on days 1-21. The perioperative regimen was repeated 2-3 times every 3 weeks. After complete resection following the perioperative EOX regimen, concurrent chemoradiotherapy with capecitabine (4,500 cGy in daily fractions of 180 cGy administered 5 days per week for 5 weeks, with 625 mg/m2 capecitabine twice daily during radiotherapy) and 2 cycles of the EOX regimen 4 weeks after radiotherapy, were performed. In total, 30/41 patients (73.2%) completed all the planned treatments, including perioperative chemotherapy, surgical resection and chemoradiotherapy. The effective rate of preoperative chemotherapy (partial and complete response) was 56.1%; 30/41 patients received R0 resection, and the overall 3-year survival rate was 57.7%. Grade 3/4 gastrointestinal toxicity (nausea/vomiting) occurred in 22% of the patients, while 18 patients (43.9%) developed grade 3/4 hematological toxicity (granulocytopenia). The results of the present study indicated that the combination of perioperative EOX chemotherapy and postoperative concurrent chemoradiotherapy is feasible and effective for locally advanced gastric cancer.

Chemotherapy combined with a tumor vaccine is an attractive approach in cancer therapy. This study was designed to investigate the optimal schedule and mechanisms of action of a novel GM-CSF (granulocyte-macrophage colony-stimulating factor) surface-modified tumor-cell vaccine in combination with paclitaxel in the treatment of mouse RM-1 prostate cancer. First, the anti-tumor efficiencies of various dosage of paclitaxel (4, 20, 40 mg/kg) in combination with the vaccine in different administration sequences were examined in the mouse RM-1 prostate cancer model. Then, the in vivo and in vitro effects of various dosage of paclitaxel on RM-1 cells, T cells, and DCs (dendritic cells) were evaluated. The results showed that: (a) the GM-CSF-surface-modified tumor-cell vaccine was more potent at inducing the uptake of tumor antigens by DCs than irradiated tumor cells plus free GM-CSF; (b) 4 mg/kg paclitaxel combined with the GM-CSF-surface-modified tumor-cell vaccine was the most effective at enhancing tumor regression in RM-1 prostate cancer mice when the vaccine was administrated 2 days after paclitaxel; and (c) administration of 4 mg/kg paclitaxel followed by the vaccine induced the highest degree of CD8(+) T-cell infiltration in tumor tissue, suggesting that the induction of tumor-specific immune response had occurred. These findings suggested that the GM-CSF-surface-modified tumor-cell vaccine may have potential clinical benefit for patients with prostate cancer when it is combined with paclitaxel. Furthermore, the effect of immunochemotherapy depends on careful selection of paclitaxel dosage and the sequence of paclitaxel/vaccine administration.

e16028Background: Some studies have shown that number of metastatic sites is a significant prognostic factor in metastatic gastric cancer. In this subgroup analysis, data from a large phase IV tria...

4039Background: Ahead-G201, a multicenter Phase IV study, is conducting to evaluate apatinib as third-line or beyond therapy in a routine practice setting of gastric cancer patients (pts). Methods:...

e16027Background: Studies have shown BMI could affect long-term survival in advanced gastric cancer. In this analysis, based on a large population, we further investigated the effects of BMI on the...

e16020Background: Apatinib has been approved in China for patients (pts) with advanced or metastatic gastric and gastro-esophageal junction adenocarcinoma after at least two lines of systemic chemo...

e16026Background: Apatinib, a small molecule VEGFR TKI, has been approved in the treatment of advanced gastric cancer in China. The real benefits of apatinib for different patients (pts) with ECOG ...

e16019Background: An open-label, multicenter, post-marketing Phase IV study of apatinib (Ahead-G201; ClinicalTrials.gov: NCT02426034) is being conducted in a broad range of gastric cancer patients ...

e16021Background: Apatinib is a small molecule tyrosine kinase inhibitor that targets VEGFR-2. Due to good safety, tolerability and efficacy, apatinib has been approved in the treatment of pretreat...

e16022Background: Hypertension (HTN) is one of the most common adverse events (AEs) associated with apatinib treatment in gastric carcinoma. However, few studies focus on the effect of HTN history ...