The ASCO Annual Meeting 2015 was held in Chicago on May 31, 2015. appropriate way to handle patients. In the field of bowel cancer, there are some research results that bring insights to our clinical work and are innovative for the research field, and some of the results are reviewed in this paper for your reference. In this meeting, Dr. Deng Le from Johns Hopkins Hospital presented the latest progress of anti-PD-1 antibodies for intestinal cancer – “PD-1 blockade in tumors with mismatch repair defects” (PD-1 blockade in tumors with mismatch repair defects). blockade in tumors with mismatch repair deficiency). This clinical study (study NCT01876511) is a 41-case, single-arm, phase II study, but the New England Journal of Medicine (NEJM) published the full study online the same day (Le, et al. NEJM, 2015; May 30; DOI: 10.1056/NEJMoa1500596), and can be considered to represent a milestone in immunotherapy. a milestone in immunotherapy. In the NCT01876511 study, patients were divided into three groups for single-arm treatment based on MMR (DNA mismatch repair) status: i.e., bowel cancer with MMR mutation (dMMR), bowel cancer with normal MMR (pMMR), and other tumors with dMMR. Patients with advanced bowel cancer who had already failed all current standard treatments were entered into this study to receive treatment with the anti-PD-1 antibody Pembrolizumab (a product of Merck Sharp & Dohme, trade name Keytruda) (administration: 10 mg/kg administered intravenously every 2 weeks). The primary study endpoints were irORR (immune-related objective response rate) and irPFS (immune-related progression-free survival) at 20 weeks. The aim of this study was to find the value of MMR status-guided anti-PD-1 immunotherapy in advanced tumors. Patients were divided into three groups to receive treatment: 11 in the dMMR bowel cancer group, 21 in the pMMR bowel cancer group, and 9 in the dMMR other tumor group (specifically, 4 potbelly/bile duct cancers, 2 endometrial cancers, 2 small bowel cancers, and 1 gastric cancer). The 20-week irORR in the three groups were: 40%, 0, and 71%, respectively; 20-week irPFS were: 78%, 11%, and 67%, respectively; ORR and DCR assessed by RECIST criteria in the three groups were: 40% and 90% in the dMMR bowel cancer group; 0 and 11% in the pMMR bowel cancer group; and 71% and 71% in the dMMR other tumor group. median PFS and OS were not achieved in the dMMR group, while they were 2.2 and 5.0 months in the pMMR bowel cancer group, respectively, both of which were statistically significant. Genome-wide tumor somatic mutation analysis was also performed in this study. dMMR tumors showed a mean of 1782 mutations and pMMR tumors showed a mean of 73 mutations. There was a significant difference between the two (p = 0.007) and the number of mutations was also significantly associated with PFS (p = 0.02). The immune modification of intestinal cancer by dMMR versus pMMR was different for the same histological types; different histological types, endometrial, gastric, cholangiocarcinoma and small intestine cancer, had tumor immune status that was more easily recognized by the body’s immune system due to the presence of dMMR at the genetic level, making immunotherapy effective. Anti-PD-1 immunotherapy based on dMMR will be a breakthrough in immunotherapy, which will be innovative not only in the field of intestinal cancer, but also expected to make new discoveries in other tumors and be able to guide clinical treatment as soon as possible, so that patients’ lives can be prolonged and their quality of life can be improved! 2. Neoadjuvant therapy and bowel cancer (FOWARC study) Preoperative 5-FU-based radiotherapy is the standard treatment for locally advanced rectal cancer. 5-FU is a radiotherapy sensitizer, but it is not effective for distant metastases. It is unknown whether full-dose mFOLFOX6 systemic neoadjuvant chemotherapy combined with concurrent radiotherapy will improve outcomes and patient survival. Radiotherapy can cause some problems such as anal and sexual impairment without providing additional long-term survival benefit. To avoid unnecessary radiotherapy, Prof. Wang Jianping and others at the Sixth Hospital of Sun Yat-sen University investigated mFOLFOX6 as a strategy for neoadjuvant therapy and reported at the congress the preliminary results of the FOWARC study: a multicenter randomized controlled study of mFOLFOX6 combined with or without radiotherapy for neoadjuvant treatment of locally progressive rectal cancer. The 495 cases of locally progressive rectal cancer were randomized into three groups: 5-FU chemotherapy + radiotherapy group, mFOLFOX6 chemotherapy + radiotherapy group, and mFOLFOX6 chemotherapy alone group. The pathological complete remission rate (pCR) was highest in patients in the mFOLFOX6 chemotherapy + radiotherapy group compared with the 5-FU chemotherapy + radiotherapy group and the mFOLFOX6 chemotherapy alone group (12.5%, 7.4%, and 31.3%, respectively; P = 0. 001), and there were no statistically significant differences in tumor R0 resection and stage reduction rates between the three groups. It was concluded that neoadjuvant treatment with mFOLFOX6 concurrent with radiotherapy for locally advanced rectal cancer resulted in improved pCR, improved remission rates, slightly increased toxicity and no decrease in compliance compared with the 5-FU monotherapy regimen. mFOLFOX6 neoadjuvant treatment for locally advanced rectal cancer had similar R0 resection rates, similar remission rates, lower surgical complication The FOWARC study is a multicenter randomized controlled phase III clinical study of rectal cancer patient characteristics in China and is the first large study of neoadjuvant treatment for bowel cancer in Chinese. This simultaneous radiotherapy can replace the existing standard treatment, but there are still 35% of patients who may not need radiotherapy to obtain a good surgical margin status. For this study, we are more concerned about the results of five-year survival rate, local recurrence rate and disease-free survival, which may provide an important reference for the revision of clinical treatment standards for rectal cancer. 3. Targeted therapy and bowel cancer (HERACLES study) Studies of patient-derived mCRC allografts have shown that HER2 amplification is a driver of cetuximab resistance. Patient-derived allograft mCRC was sensitive to dual HER2 blocking therapy with lapatinib and trastuzumab, but not to any single blocking therapy. Italian medical doctors reported at the congress on the HERACLES study: a clinical study II of trastuzumab (T) and lapatinib (L) combination in patients with HER2 amplified, KRAS gene exon 2 wild type metastatic colorectal cancer. This study includes patients with metastatic colorectal cancer that has progressed after treatment with fluorouracil, oxaliplatin, irinotecan, bevacizumab, cetuximab or panitumumab and is HER2+ [ IHC2+ with concurrent FISH positive (HER2:CEP17 > 2) >50% cells or IHC3+]. The study was conducted by oral administration of lapatinib once daily and intravenous administration of trastuzumab once weekly; both at standard doses. Efficacy was assessed every 8 weeks. The primary endpoint of the study was objective response (OR, RECIST v1.1). 913 patients were screened for this study, and 44 (4.8%) were HER2-positive, of whom 23 met the evaluation criteria. The primary endpoint ORs were 8/23 [7 PR, 1 PRunc (short duration); ORR=35%]; the duration of efficacy in the 8 patients with PR was 8+, 12+, 14+, 24, 24.5+, 32, 54+ and 55+ weeks, respectively. The median time to disease progression was 5.5 months (95% CL 3.7-9.8). Toxic side effects were manageable. For patients with KRAS gene exon 2 wild-type mCRC, 5% have HER2 gene amplification. HERACLES study showed that for this group of patients, dual anti-HER2 therapy is effective and dual blockade of HER2 is a valuable novel treatment for HER2+ mCRC. 4. Adjuvant therapy and bowel cancer (PETACC8 and NCCTG N0147 studies) Aziz Zaanan reported to the congress on the following topic: Results of DNA mismatch repair (MMR) and clinical prognosis analysis in stage III colon cancer in patients treated with FOLFOX+/- cetuximab. This study pooled data from 2 large randomized adjuvant studies: NCCTG N0147, PETACC-8. The aim was to evaluate the prognostic impact of MMR status in patients with stage III colon cancer receiving FOLFOX-based adjuvant therapy, including disseminated and familial MSI subtypes. The investigators measured MMR protein (MLH1, MSH2, MSH6) expression and BRAF (V600E) mutations, respectively. Any MMR protein deletion represented a MMR defect (dMMR). Methylation of the MLH1 gene promoter was analyzed in tumors with MLH1 deletion and BRAF gene wild type (WT). the status of MMR was analyzed in correlation with clinical prognostic indicators such as overall survival (OS). The results of the study can be referred to the following table: This study found that MSI was not a significant prognostic factor in stage III colon cancer patients receiving FOLFOX-based adjuvant chemotherapy, and MMR status was not associated with prognosis. In subgroup analysis, MSI was a prognostic factor for DFS and OS for the FOLFOX adjuvant chemotherapy alone subgroup; it was not for the FOLFOX+cetuximab adjuvant chemotherapy subgroup. In the MSI population, clinical outcomes were worse in disseminated cases than in familial cases. It is of scientific interest to further investigate the reasons for the role of cetuximab in influencing the prognostic judgment of MSI. 5. Genomics and Bowel Cancer (Abstract No. 3506) Marios Giannakis et al. reported this study (Abstract No. 3506) at the Congress: Comprehensive Molecular Characterization of Colorectal Cancer Reveals Genomic Predictors of Immune Cell Infiltration. The background of this study is based on the fact that colorectal cancer (CRC) is a molecularly heterogeneous disease that occurs and develops in a complex set of microenvironments. While tumor immune cell infiltration has been shown to be associated with improved overall survival, the genomic features of intestinal cancer that determine the number and type of immune infiltrates have not been clearly characterized. Immune construct composition is of prognostic importance in colorectal cancer, and neoantigens have been identified in other malignancies to predict response to immunotherapy. This study selected 689 patients with primary colorectal cancer from two large prospective cohort studies, in which whole-exome sequencing and microsatellite instability analysis were performed. The investigators also characterized immune infiltration by immunohistochemistry and performed tissue microarray imaging analysis of T-cell subsets. The investigators utilized a novel computational pathway to calculate tumor neoantigen load and correlated tumor neoantigen load with the above immune variables and patient survival. Tumors with highly unstable microsatellites significantly expressed more neoantigens compared to microsatellite stable tumors (P < 2e-16). Higher tumor neoantigen load predicted higher overall survival (P=0.048). Neoantigen load is an independent prognostic factor for colorectal cancer-specific survival. Tumor neoantigen load may serve as a novel genomic predictor of survival in CRC patients and has implications for subsequent treatment decisions in CRC.