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Background Hepatocellular carcinoma (HCC) is one of the most common malignancies in China with poor prognosis. Recently, personalized neoantigen-based immunotherapy has been reported to induce robust anti-tumor immune responses to facilitate tumor rejection in several solid tumors. However, whether it possess therapeutic potential in HCC still remain unclear. Thus, a systemic understanding of neoantigen burden (TNB) in HCC microenvironment is in need. Methods HCC and matched peritumor tissue collected from 59 HCC patients were subjected to DNA and RNA sequencing for identifying tumor associated neoantigens. Then the association between neoantigens and clinical features, immune signatures, as well as clonal evolution patterns in HCC were evaluated. Results In enrolled HCC patients, a median of 106 somatic mutations and 15 neoantigens were identified in each patient. TNB was significantly correlated with tumor somatic mutation burden (R2 = 0.893, P = 3.0 × 10^-24). Furthermore, the clinicopathological analysis revealed that patients with higher TNB was characterized with older age (p = 0.006), decreased tumor size (p = 0.020) and lower recurrence rate (p = 0.019). Additionally, TNB was also significantly associated with relapse free survival (P = 0.033) and overall survival (P = 0.022) in HCC patients. Surprisingly, HCC tumor with high immune cell infiltration were more likely to have no tumor envelope (P = 0.027) and resulted in shorter overall survival time after surgery (P = 0.025); the patients with lower immune cell signatures related to antigen-processing have relatively higher TNB in HCC. Meanwhile, clonal evolution analysis revealed that the clonal mutations were more likely to be neoantigens (P = 9.2 × 10^-5) than subclonal mutations, suggesting higher immunogenicity for clonal mutations. And tumors with higher proportion of neoantigens in clonal mutations were more likely to involved in clonal evolution, which may due to the immunoediting of neoantigens (P = 0.002). Conclusions Our results demonstrated that neoantigens play an important role in tumor clonal evolution and immune response in HCC, which could provide insights for future HCC immunotherapy. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background The prognostic predictive value of breast cancer susceptibility gene 1 (BRCA1) for non-small-cell lung cancer (NSCLC) remains controversial. This study aimed to determine the prognostic effect of BRCA1 on NSCLC survival using meta-bioinformatic analysis. Methods Candidate articles were identified from PubMed, Embase, Cochrane Library, and Web of Science databases. Effect measures generated were the pooled hazard ratio (HR) and 95% confidence interval (CI). Cox regression model was performed in an independent dataset from TCGA to validate the accuracy of our meta-analysis. Results A total of 2462 patients from 15 studies of acceptable quality were included. No significant differences in overall survival (OS)/cancer-specific survival (CSS) (HR = 1.38, 95% CI: 0.95-2.00, P = 0.094) or progression-free survival (PFS)/disease-free survival (DFS)/relapse-free survival (RFS) (HR = 1.28, 95% CI: 0.82-2.00, P = 0.284) were observed between patients with high- and low-expression of BRCA1. However, patients with lung adenocarcinoma (LUAD) and increased BRCA1 expression had markedly poorer OS/CSS (HR = 1.78, 95% CI: 1.05-3.03, P = 0.032) than those with reduced BRCA1. Bioinformatics analysis also indicated that BRCA1 overexpression was independently correlated with decreased OS in LUAD. Moreover, patients with high BRCA1 were more likely to suffer from lymph node metastasis than those with low BRCA1. Conclusions Elevated BRCA1 expression may be a novel biomarker of poor OS for patients with LUAD. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background Hepatocellular carcinoma (HCC) is the most common malignancy with high rates of recurrence and metastasis after radical resection. Vascular invasion, including portal vein tumor thrombus (PVTT) and microvascular invasion (MVI), and microsatellite lesions are two significant risk factors of postoperative recurrence and metastasis for HCC. Therefore, it is necessary to discover adjuvant therapies for patients with these risk factors. Anti-angiogenesis therapy combined with immunotherapy has demonstrated clinical benefits in multiple advanced solid neoplasms, including HCC. An exploratory phase Ib study (NCT02942329) proved that combined therapy of apatinib (250mg QD) and anti-PD-1 drug, SHR-1210 (200mg Q2W) was well tolerated and had preliminary efficacy in advanced HCC. Trial design This multicenter, randomized, controlled, phase II study will evaluate the safety and efficacy of adjuvant combined therapy of apatinib and anti-PD-1 drug, SHR-1210, compared with hepatic arterial infusion (HAI) chemotherapy, in patients with HCC at high risk of recurrence after radical resection. 200 patients, aged >18 years, Child-Pugh score 0 or 1, with histologically confirmed primary HCC, BCLC stage A or B diseases that are radical resected without other prior therapy for HCC and who are found to have microsatellite lesions, microvascular invasion or PVTT involved in second-order branch or above by preoperative imaging examination or postoperative pathological findings will be recruited and randomized (1:1) to receive apatinib (250mg QD) and SHR-1210 (200mg Q2W) for 6 months, or 2 times of standard HAI treatments (epirubicin 80-100mg or epirubicin 50mg+oxaliplatin 50mg). The primary endpoint is to compare recurrence-free survival and secondary endpoints include overall survival, safety, 1,2,3-year recurrence rate and Quality of Life score (QoL). Survival follow-up will continue for up to 3 years. The study is ongoing. Clinical trial identification NCT 03839550. Legal entity responsible for the study National Cancer Center/Cancer Hospital. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background Individual patient data from two multicentre, randomised trials comparing atezolizumab with docetaxel in previously treated advanced non-small-cell lung cancer (NSCLC) were analyzed to identify any preferable therapeutic approaches for patient subsets stratified by EGFR mutation status. Methods We pooled 1,137 patients from the phase II POPLAR trial (NCT01903993) and the phase III OAK trial (NCT02008227). Patients were randomly assigned to receive either atezolizumab or docetaxel and were analyzed based on stratification of EGFR mutation status. We built a novel algorithm integrating the blood-based tumor mutation burden and the ctDNA maximum somatic allele frequency (bTMB-MSAF score) and developed a novel clinicopathologic-genomic nomogram to predict individual survival. Results In the whole intention-to-treat population, OS was significantly longer with atezolizumab than with docetaxel (hazard ratio [HR] 0.72, P < 0.001). Among patients without EGFR or ALK mutations, overall survival (OS) was significantly longer with atezolizumab than with docetaxel (HR 0.67; P < 0.001); patients with a bTMB-MSAF score<20 showed improvement in OS (HR 0.56; P < 0.001) and progression-free survival (PFS) (HR 0.74; P = 0.0023), and these patients who concurrently had programmed death ligand 1 (PD-L1) expressing on over 50% tumor cells or over 10% of tumor-infiltrating immune cells (TC3 or IC3) had the greatest OS improvements (HR 0.44; P = 0.007) and promising PFS benefits (HR 0.54; P = 0.019). EGFR mutant patients could not gain significant OS or PFS benefits from atezolizumab over docetaxel, irrespective of PD-L1 expression and bTMB-MSAF score. Patients with low-risk scores had longer OS (HR 0.17; P < 0.001; AUC=0.912 for 3-year OS) than patients with high-risk scores classified by the nomogram. Conclusions Atezolizumab showed better OS and PFS than docetaxel in previously treated EGFR wild-type NSCLC patients with a bTMB-MSAF score < 20, especially in those with PD-L1 expression of TC3 or IC3. Our clinicopathologic-genomic nomogram is effective in predicting survival of NSCLC patients undergoing atezolizumab. Clinical trial identification NCT01903993 and NCT02008227. Legal entity responsible for the study Herui Yao. Funding Herui Yao is funded by the National Science and Technology Major Project under Grant [2020ZX09201021]; National Natural Science Foundation of China under Grant [81372819, 81572596, U1601223]; Natural Science Foundation of Guangdong Province under Grant [2017A030313828]; and Guangzhou Science and Technology Program under Grant [201704020131]. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background KEYNOTE-181 (NCT02564263) was an open-label, randomized, phase 3 trial of pembrolizumab (pembro) vs investigator choice of single-agent paclitaxel/docetaxel/irinotecan (chemo) in advanced/metastatic esophageal AC or SCC. Pts were enrolled in partially overlapping periods, initially globally and then in China with an extension period. We present results from the global and China cohorts. Methods Pts were randomized 1:1 to receive pembro or chemo. Randomization was stratified by histology (SCC vs AC) and region (Asia vs rest of world). Primary end points were OS in the ITT, SCC, and PD-L1 CPS ≥10 populations. Results There were 628 and 123 pts in the global and China cohorts, respectively. In the global cohort, 314 pts were randomized to receive pembro (199 [63%] had SCC; 107 [34%] had CPS ≥10 tumors); 314 pts to chemo (204 [65%] had SCC; 115 [37%] had CPS ≥10 tumors). Median follow-up was 7.1 mo (pembro) vs 6.9 mo (chemo). Median OS with pembro vs chemo was similar in the ITT group (7.1 vs 7.1 mo) and longer in the SCC (8.2 vs 7.1 mo) and CPS ≥10 groups (9.3 vs 6.7 mo). 12-month OS rates were higher with pembro in all groups (ITT 32% vs 24%; SCC 39% vs 25%; CPS ≥10 42% vs 20%). In the China cohort, 62 pts were randomized to pembro (60 had SCC; 25 had CPS ≥10 tumors); and 61 pts to chemo (59 had SCC; 29 had CPS ≥10 tumors). Median follow-up was 8.3 mo (pembro) vs 5.6 mo (chemo). Median OS was higher with pembro in the ITT (8.4 vs 5.6 mo; HR 0.55; 95% CI 0.36-0.82), SCC (8.4 vs 5.6 mo; HR 0.55; 95% CI 0.37-0.83), and CPS ≥10 groups (12.0 vs 5.3 mo; HR 0.34; 95% CI 0.17-0.69). 12-month OS rates were higher with pembro in all groups (ITT 36% vs 17%; SCC 36% vs 16%; CPS ≥10 53% vs 16%). Fewer pts had TRAEs with pembro than chemo (global 64% vs 86%; China 76% vs 83%). TRAE rates resulting in discontinuation with pembro vs chemo were comparable in the global cohort (6% each) and lower with pembro in the China cohort (6% vs 12%). Conclusions Pembro and chemo showed comparable OS as 2L therapy for esophageal AC/SCC in the global ITT cohort. Pembro showed favorable OS in SCC and CPS ≥10 groups in the global cohort and in all groups in the China cohort, in which most patients had SCC. Pembro showed favorable safety in both cohorts. Clinical trial identification NCT02564263. Editorial acknowledgement Medical writing and/or editorial assistance was provided by Traci Stuve, MA, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp. a subsidiary of Merck & Co. Inc. Kenilworth, NJ, USA. Legal entity responsible for the study Merck Sharp & Dohme Corp. a subsidiary of Merck & Co. Inc. Kenilworth, NJ, USA. Funding Merck Sharp & Dohme Corp. a subsidiary of Merck & Co. Inc. Kenilworth, NJ, USA. Disclosure S-B. Kim: Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Sanofi-Aventis; Research grant / Funding (institution): Kyowa-Kirin; Research grant / Funding (institution): DongKook Pharmaceutical. T. Doi: Advisory / Consultancy: Kyowa Hakko Kirin, MSD, Daiichi Sankyo, Amgen, Sumitomo Dainippon, Taiho Pharmaceutical, Takeda, AbbVie, Novartis, Bayer; Research grant / Funding (institution): Taiho Pharmaceutical, Novartis, Merck Serono, MSD, Boehringer Ingelheim, Pfizer, Lilly Japan, Sumitomo Group, Kyowa Hakko Kirin, Daiichi Sankyo, Bristol-Myers Squibb, AbbVie, Quintiles, Eisai. K. Kato: Research grant / Funding (institution): MSD, ONO Pharmaceutical, Shionogi, Merck Serono. M. Shah: Research grant / Funding (institution): Merck, Roche, Boston Biomedical. A. Adenis: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Servier. T. Kojima: Non-remunerated activity/ies, Other- Patents, Royalties, other Intellectual Property: Ono Pharmaceutical, MSD, Shionogi Pharma, Oncolys BioPharma, Astellas Amgen BioPharama; Honoraria (self): Oncolys BioPharma. J-P. Metges: Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Merck; Honoraria (self): Bayer-Health; Honoraria (self): Lilly; Advisory / Consultancy: ERYTECH Pharma; Advisory / Consultancy: Sanofi. E. Francois: Research grant / Funding (institution): MSD; Non-remunerated activity/ies, +Personal Fees: Roche; Non-remunerated activity/ies, +Personal Fees: Servier; Non-remunerated activity/ies, +Personal Fees: Merck; Non-remunerated activity/ies, +Personal Fees: Amgen; Non-remunerated activity/ies, +Personal Fees: Sanofi; Non-remunerated activity/ies, +Personal Fees: Novartis; Non-remunerated activity/ies, +Personal Fees: Bayer. K. Muro: Honoraria (self): Takeda, Chugai Pharma, Yakult Honsha, Merck Serono, Taiho Pharmaceutical, Lilly, Ono Pharmaceutical, Bayer; Research grant / Funding (institution): Ono Pharmaceutical, MSD, Daiichi Sankyo, Shionogi, Kyowa Hakko Kirin, Gilead Sciences, Merck Serono, Pfizer, Sanofi. R. Wang: Full / Part-time employment: Merck & Co. Inc. Y. Cui: Full / Part-time employment: MSD China. P. Bhagia: Full / Part-time employment: Merck & Co. Inc. All other authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]