Search

Background Oxaliplatin as part of XELOX regimen has a more favorable toxicity profile than cisplatin for patients with advanced gastric cancer (GC). However, oxaliplatin can induce sensory neuropathy, a cumulative, dose-related toxicity. Thus, capecitabine maintenance regimen might achieve maximum treatment effect while reducing cumulative neurotoxicity of oxaliplatin. The aim of this study was to compare survivals of AGC patients between capecitabine maintenance and observation after 1st line XELOX chemotherapy. Methods Sixty-three patients treated with six cycles of XELOX for AGC in six hospitals of the Catholic University of Korea were randomized 1:1 to capecitabine maintenance or observation. The primary end point was PFS (PFS) analyzed using a two-sided log-rank test stratified at 5% significance level. Results Between 2015 and 2020, 32 and 31 patients were randomized to maintenance and observation groups, respectively. After randomization, the median number of cycles for maintenance capecitabine was 6. PFS was significantly higher for the maintenance group (6.3 months vs. 4.1 months, P = 0.010). OS (OS) was not significantly different between the two groups (18.2 months vs. 16.5 months, P = 0.624). Toxicity such as hand-foot syndrome was reported in some cases of the maintenance group. Maintenance treatment was a significant factor associated with PFS in multivariate analysis (HR: 0.472, 95% CI: 0.250-0.890, P = 0.020). Conclusions After six cycles of XELOX chemotherapy, capecitabine maintenance significantly prolonged PFS than observation and toxicity was manageable. Maintenance treatment was a significant prognostic factor associated with PFS.

Introduction: There are similar and different properties between the epidermal growth factor receptor mutations (mEGFR), which are classified into common, uncommon, and compound mutation subtypes depending on their location and pattern on the EGFR gene. We investigated the RWD and RNA expression profile of non-common mutations (uncommon and compound mutations) in the mEGFR+ NSCLC patients. Method: We analyzed the NGS data extracted from the Foundation Medicine (FMI) SRC. And, we collected the medical information for stage I-IIIA mEGFR+ NSCLC patients receiving curative surgical resection. In Böehringer Ingelheim (BI) open data access (ODA), we analyzed treatment results in stage IV mEGFR+ NSCLC patients treated with EGFR TKI. We explored the RNA expression profile by High-Plex Digital Spatial Profiling. A total of 18,676 DEG libraries were constructed, and 419 significance genes with > 2-fold changes, 3-log 2 normalized read counts, and p-value = 0.05 (up and down) were identified. Result: In FMI-SRC cohort, 10,059 mEGFR+ cases of total 78,656 cases consist of common, 6,994 (69.5%), uncommon, 1,966 (19.6%), and compound, 1,099 (10.9%). In hospital cohort, 941 mEGFR+ cases consist of common, 860 (91.4%), uncommon, 60 (7.4%), and compound, 21 (2.2%). Median relapse-free survival (mRFS) in non-common mutations (31.4M and 33.7M) was shorter than common mutations (40.1M, p=0.877). CNS recurrence in the non-common mutations (40.0% and 35.3%) tended to be higher than that of common mutations (27.4%, p=0.361). In BI-ODA, median time on treatment (mTOT) in 163 uncommon mutations (10.0M) and 139 compound mutations (11.5M) were shorter than historical data of common mutations (17.3M). Spatial RNA-seq data of the ratio of deconvolution individual cells showed that genes involved in inflammatory and immune response were relatively lower in non-common mutations. Gene ontology string analysis revealed RNA expression of genes in compound mutations was functionally associated with chemokine production (23.4%), electron transfer activity (14.9%) and T cell selection (8.5%), and, in uncommon mutations, was associated with regulation of oligopeptide transport (26.1%), hypermethylation of CpG island (21.7%), and CD4+ CD25+ regulatory T cell lineage commitment (13.0%), compared to common mutations. Based on the GSEA, relatively highly clustered genes in compound mutations were the protein modification process, G-protein coupled receptor, regulation of cytosolic calcium ion concentration, and IL-5 production pathways, and lower ES levels in oxidative phosphorylation and RNA processing pathways, when compared to common mutations. Conclusion: Taken together, our results suggest that uncommon and compound mEGFR subtypes exhibiting shorter mRFS and mTOT, and distinguishing RNA expression profile of functional signaling pathways be not same disease entity as common mEGFR subtype Citation Format: Seoree Kim, Yeoun Eun Sung, Joo Ri Kim, Chan Kwon Jung, Jeong-Oh Kim, Jeong-yeon Shin, Guk Jin Lee, Sang hoon Chun, Young Ho Lee, Jin Hyoung Kang. Real world data and multi-genomic analysis of non-common mutations in the EGFR mutation-positive non-small cell lung cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4391.

e21504 Background: The immune checkpoint inhibitors (ICIs), have improved survival with durable response for advanced malignant melanomas, but, only a minority of patients has achieved. To stay sway failure of triage patients, considerable side effects and costs of ICB therapies, the development of robust signatures predictive of response to ICB therapies is warranted. Methods: Clinical data were collected at Seoul St. Mary’s Hospitals. Among them, we examined RNA expression profile by QuantSeq 3’ mRNA-Sequencing and the composition, and spatial distance of immune cells by multiplex immunofluorescent staining. Results: The gene sets with relatively higher RNA expression in the good response group, were as follows; hematopoietic cell dedifferentiation gene, T-cell related adaptive immunity gene, IFN-related cytokine gene, and macrophage (TAM), NK cell, innate immunity gene set. Meanwhile, in the poor response group, inflammatory response, fibrosis response genes was increased.The cell densities of T cells, cytotoxic T cells, Treg cells, CD8+Treg cells, and exhausted T cells in the good response group tended to be higher, which was clearer in the peritumoral (PT) area than the intratumoral (IT) area. For the good response group, M1/M2 ratio in the IT area was significantly higher compared to that of poor response group (p = 0.045). According to the nearest neighbor analysis for % of melanoma cells within 15um distance present a close distance from M1, M2, and NK cells tended to be higher in the IT area than PT area. For the cases with higher spatial distribution from M1 in the IT area, PFS and OS was significantly extended (PFS, p = 0.0021; OS, p = 0.036). The gene sets with relatively higher mRNA expression in high neighborhood macrophage group, were cell death, apoptosis process gene set. In low neighboring M1 macrophage group, relatively higher mRNA expressions of extracellular component inflammation and fibrosis gene, cell migration, and cell de-differentiation gene set were observed. Conclusions: Taken together, our results suggest 4 key points. First, good and poor responder groups for ICB show marked differences from mRNA profiling to protein expression according to central dogma. Second, immune cells can be distributed sporadically in many places, but the actionable ground of the adaptive immune cells of the T cell family is the PT, and the playground of innate immune cells such as TAM and NK cells is the IT. In particular, the anti-tumor response of M1 macrophage and M2 macrophage was oppositely in IT. Third, high TAMs in IT are interpreted to have a tumoricidal effect because they show a stationery state while coding the killing effect gene set. In addition, topologically, spatial analysis as well as bulk genomics are important for predicting tumor response for ICIs.

e12528 Background: The treatment of male breast cancer (MBC) has been extrapolated from female breast cancer (FBC) because of its rarity despite their different clinicopathologic characteristics. We aimed to investigate the distribution of intrinsic subtypes based on immunohistochemistry (IHC), their clinical impact, and treatment pattern in clinical practice through a multicenter study in Korea. Methods: We retrospectively analyzed clinical data of 248 MBC patients 18 institutions across the country from January 1995 to July 2016. Results: The median age of MBC patients was 63 years (range: 25–102 years). Among the 148 patients that underwent intrinsic subtype classification, 61 (41.2%), 44 (29.7%), 29 (19.5%), and 14 (9.5%) were luminal A, luminal B, HER2, and triple-negative breast cancer (TNBC), respectively. TNBC patients showed inferior survival compared with those with other subtypes. Of the 221 patients with operable breast cancer, 108 (48.6%) received adjuvant chemotherapy and 52 (23.5%) received adjuvant radiation therapy. Most hormone receptor-positive patients (166 patients, 82.6%) received adjuvant endocrine treatment. Five-year completion of adjuvant endocrine treatment was associated with superior disease-free survival (DFS) in patients classified with an intrinsic subtype (hazard ratio [HR] = 0.19, 95% confidence interval [CI] 0.005–0.65, P = 0.008) and in all patients (HR = 0.16, 95% CI 0.05–0.54, P = 0.003). Conclusions: Distribution of subtypes of MBC was similar to FBC and luminal type A was most common. Overall survival tended to be improved for luminal A subtype although there was no statistical significance. Completion of adjuvant endocrine treatment was associated with prolonged DFS in intrinsic subtype classified patients. MBC patients have tended to receive les treatment. MBC patients should be treated with standard guideline as FBC patients receive.