Gastroesophageal Cancer Research Articles

Top Gastric Cancer Articles from 2022 and 2023 to Inform Your Cancer Practice.

The multimodality management of patients with gastroesophageal cancers is rapidly evolving, with the introduction of new therapies against potential molecular targets paving the way to personalized medicine for patients with both resectable and metastatic disease. Over the past 2years, several important studies evaluating these new targeted therapies, as well as minimally invasive surgical approaches to gastric cancer, have been published. This review article summarizes the top studies published in gastric cancer over the past 2years that are fundamentally changing our practice approach to gastric cancer patients. First, the long-term safety and efficacy of laparoscopic distal gastrectomy as compared with open gastrectomy for locally advanced gastric cancer was confirmed with the publication of the 5-year outcomes of the CLASS-01 and KLASS-02 randomized clinical trials. In addition, several important studies of perioperative immunotherapy for patients with resectable gastric or gastroesophageal junction cancers are ongoing, and in 2022, an interim analysis of the DANTE trial and the final results of the GERCOR NEONIPIGA study were reported. Lastly, the KEYNOTE-859 and SPOTLIGHT trials address an unmet need for additional targeted therapies for patients with previously untreated, human epidermal growth factor receptor-2 (HER2)-negative, unresectable or metastatic gastroesophageal cancers, incorporating immune checkpoint inhibitors and targeting Claudin-18 isoform 2 (CLDN18.2) with the monoclonal antibody zolbetuximab, respectively. This article summarizes the findings and implications of several important studies published over the past 2years that are fundamentally changing the way we treat patients with gastroesophageal cancer.

Who Should Receive Immunotherapy for Advanced Gastroesophageal Cancer?

This paper shines a light on the exciting progress being made in using immunotherapy to treat advanced gastroesophageal cancers. The positive results from trials using drugs like Pembrolizumab and Nivolumab are certainly encouraging and open new possibilities for treating this challenging disease. However, it is clear that we still have a lot to learn about how to predict which patients will benefit most from these treatments. The exploration of combining therapies and using machine learning to guide treatment shows promise. Moving forward, it is crucial that researchers and healthcare professionals continue to work together, sharing knowledge and findings to continue the advancements in this important area.

Prognostic nutritional index in predicting survival of patients with gastric or gastroesophageal junction adenocarcinoma: A systematic review.

Gastric cancer is the third most common cause of cancer related death worldwide. Surgery with or without chemotherapy is the most common approach with curative intent; however, the prognosis is poor as mortality rates remain high. Several indexes have been proposed in the past few years in order to estimate the survival of patients undergoing gastrectomy. The preoperative nutritional status of gastric cancer patients has recently gained attention as a factor that could affect the postoperative course and various indexes have been developed. The aim of this systematic review was to assess the role of the prognostic nutritional index (PNI) in predicting the survival of patients with gastric or gastroesophageal adenocarcinoma who underwent gastrectomy with curative intent. To investigate the role of PNI in predicting the survival of patients with gastric or gastroesophageal junction adenocarcinoma. A thorough literature search of PubMed and the Cochrane library was performed for studies comparing the overall survival (OS) of patients with gastric or gastroesophageal cancer after surgical resection depending on the preoperative PNI value. The PRISMA algorithm was used in the screening process and finally 16 studies were included in this systematic review. The review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO). Sixteen studies involving 14551 patients with gastric or esophagogastric junction adenocarcinoma undergoing open or laparoscopic or robotic gastrectomy with or without adjuvant chemotherapy were included in this systematic review. The patients were divided into high- and low-PNI groups according to cut-off values that were set according to previous reports or by using receiver operating characteristic curve analysis in each individual study. The 5-year OS of patients in the low-PNI groups ranged between 39% and 70.6%, while in the high-PNI groups, it ranged between 54.9% and 95.8%. In most of the included studies, patients with high preoperative PNI showed statistically significant better OS than the low PNI groups. In multivariate analyses, low PNI was repeatedly recognised as an independent prognostic factor for poor survival. According to the present study, low preoperative PNI seems to be an indicator of poor OS of patients undergoing gastrectomy for gastric or gastroesophageal cancer.

Clinicopathological characterisation of MTAP alterations in gastrointestinal cancers

BackgroundMethylthioadenosine phosphorylase (MTAP) is an essential metabolic enzyme in the purine and methionine salvage pathway. In cancer, MTAP gene copy number loss (MTAP loss) confers a selective dependency on the...

American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium 2024: Gastro-oesophageal Cancer in Focus

American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium 2024: Gastro-oesophageal Cancer in Focus

Efficacy and safety of anti-programmed death-1 antibody-based combination therapy in advanced or metastatic gastric or gastroesophageal junction cancer in Chinese patients: A real-world study.

Programmed death-1 antibody plus chemotherapy has gained approval for the treatment for (human epidermal growth factor receptor 2 negative locally advanced or metastatic gastric or gastroesophageal junction cancer. This study aims to analyze the efficacy and safety of anti-programmed death-1 antibody combined with chemo- or anti-angiogenesis therapy in Chinese patients with advanced or metastatic gastric or gastroesophageal junction cancer in a real-world setting. In total, 122 patients treated with anti-programmed death-1 antibody-based combination therapy between April 2019 and December 2021 were encompassed. Clinical outcomes and safety profile were measured and analyzed. In the whole cohort, median overall survival was 17.2 months, median progression-free survival was 10.9 months, and median duration of response was 9.4 months. Notably, in the first-line patients, the median overall survival was not reached, median progression-free survival was 14.8 months, objective response rate was 68.4%. In the second-line group, median overall survival, median progression-free survival, median duration of response, and objective response rate were 10.9 months, 5.9 months, 4.5 months, and 41.5%, respectively. Treatment-related adverse events of any grade were observed in 28.2% of the overall cohort, primarily affecting the hematological and liver function. Grade 3 or 4 adverse events were mainly characterized by increased levels of aspartate aminotransferase, alanine aminotransferase, along with decreased lymphocyte and white blood cells, as well as anemia. Patients in our cohort experienced a clinical benefit from anti-programmed death-1 antibody-combined treatment in first-line treatment settings, with acceptable treatment-related adverse events. The benefit of anti-programmed death-1 antibody combined with chemo- or anti-angiogenesis treatment to the second-line patients should be further confirmed by large multi-center randomized, controlled clinical trials.

A phase 1, first-in-human, dose-escalation and expansion study of FX-909 in patients with advanced solid malignancies, including advanced urothelial carcinoma.

TPS709 Background: High Expression of Peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor-family transcription factor, drives the initiation and development of UC in luminal molecular subtype tumors. Genetic profiling of UC has identified recurrent oncogenic alterations in the PPARG transcriptional complex, including focal amplification, missense mutations, and fusions in the heterodimeric partner of PPARG, the retinoid X receptor alpha (RXRA). High levels of PPARG expression and recurrent oncogenic alterations are observed in other solid malignancies including colorectal, gastroesophageal, pancreatic and lung cancers. FX-909 is an oral, first-in-class, new molecular agent that specifically, potently, and covalently modifies PPARG to mediate basal and ligand-activated transcription. Treatment of genetically defined UC xenografts with FX-909 has shown an 84% tumor growth inhibition (TGI) at a dose expected to be equivalent to 50 mg dose in humans, which is the starting dose in this clinical study. Methods: FX-909-CLINPRO-1 (NCT05929235) is a first-in-human, multicenter, open-label Phase 1 study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of FX-909 given orally in patients with advanced solid malignancies. Patients enrolled in the trial must have ECOG performance status ≤2 and must be ≥ 18 years of age. Initially, FX-909 will be given once daily to patients with any advanced solid malignancy in a dose-escalation phase (Part A) utilizing a 3+3 design. Five dose cohorts of 3 to 6 patients are planned. At the time of submission, three patients are enrolled in Part A- cohort one, 50mg. Additional patients will be allowed to backfill to previously cleared dose levels that demonstrate therapeutically relevant exposures or evidence of clinical activity. Once a RP2D has been determined, a monotherapy expansion phase (Part B) will proceed in a Simon 2-stage design in patients with locally advanced (unresectable) or metastatic UC with measurable disease and tumors harboring defined genetic alterations in PPARG, RXRA and FGFR3 (Motley et al, 2022). In stage 1, up to 19 evaluable patients will be enrolled. If ≥4 objective responses are observed, enrollment will continue into Stage 2 with an additional 14 evaluable patients. One treatment cycle is 28 days. Dose expansion will evaluate the safety, PK/PD profile, and antitumor activity of FX-909 at the RP2D. Exploratory objectives include the evaluation patient selection biomarkers from tissue and blood samples. FX-909 clinical activity will be assessed using RECIST v1.1 criteria. The study is currently enrolling patients in the US. Clinical trial information: NCT05929235 .

Rivoceranib, a VEGFR-2 inhibitor, monotherapy in previously treated patients with advanced or metastatic gastric or gastroesophageal junction cancer (ANGEL study): an international, randomized, placebo-controlled, phase 3 trial

BackgroundRivoceranib is an oral, selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2. ANGEL (NCT03042611) was a global, randomized, double-blinded, placebo-controlled, phase 3 study evaluating rivoceranib as 3rd-line or ≥4th-line therapy in patients with advanced/metastatic gastric or gastroesophageal junction (GEJ) cancer.MethodsPatients had failed ≥2 lines of chemotherapy and were randomized 2:1 to rivoceranib 700 mg once daily or placebo with best supportive care. Primary endpoint: overall survival (OS) in the intention-to-treat population. Secondary endpoints: progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) by blinded independent central review (BICR).ResultsIn total, 460 patients (rivoceranib n = 308, placebo n = 152) were enrolled. OS was not statistically different for rivoceranib versus placebo (median 5.78 vs. 5.13 months; hazard ratio [HR] 0.93, 95% CI 0.74–1.15; p = 0.4724). PFS by BICR (median 2.83 vs. 1.77 months; HR 0.58, 95% CI 0.47–0.71; p < 0.0001), ORR (6.5% vs. 1.3%; p = 0.0119), and DCR (40.3 vs. 13.2%; p < 0.0001) were improved with rivoceranib versus placebo. In patients receiving ≥4th-line therapy, OS (median 6.34 vs. 4.73 months; p = 0.0192) and PFS by BICR (median 3.52 vs. 1.71 months; p < 0.0001) were improved with rivoceranib versus placebo. The most common grade ≥ 3 treatment-emergent adverse events with rivoceranib were hypertension (17.9%), anemia (10.4%), aspartate aminotransferase increased (9.4%), asthenia (8.5%), and proteinuria (7.5%).ConclusionsThis study did not meet its primary OS endpoint. Compared to placebo, rivoceranib improved PFS, ORR, and DCR. Rivoceranib also improved OS in a prespecified patient subgroup receiving ≥4th-line therapy.

Retrospective cohort study to evaluate the efficacy and safety of T-DXd in HER2-positive unresectable advanced or recurrent gastric or gastroesophageal junction cancer: EN-DEAVOR study.

274 Background: Relatively limited clinical data exists for patients who receive T-DXd treatment in the 3L+ setting for HER2-positive unresectable advanced/recurrent gastric or gastroesophageal junction cancer. Insufficient data exists on real world patient populations that are likely to be excluded from clinical trials (e.g., elderly patients, those with significant co-morbidities). Therefore, this study was designed to evaluate the real-world clinical effectiveness and safety of T-DXd in patients with HER2-positive gastric cancer. Methods: This study (UMIN000049032) was a real-world, multicenter, non-interventional, retrospective cohort study conducted in Japan. Patients with HER2-positive unresectable advanced/recurrent gastric or gastroesophageal junction cancer treated with T-DXd were enrolled. The patients were first administered T-DXd between Sep 2020, when T-DXd became available for clinical use in Japan, and Sep 2021. We followed up on these patients' records until Sep 2022. The endpoints were overall survival (OS), real-world progression-free survival (rwPFS), time to treatment failure (TTF), objective response (ORR), adverse events (AEs) of Grade ≥3, and adverse events leading to dose reduction, interruption, or discontinuation. Results: A total of 318 patients were enrolled, and 312 patients were analyzed, excluding 6 patients due to double enrollment or miss-enrollment (median age 70 years, performance status 0 or 1/≥2 [87%/12%], 43% patients with ascites). Median OS, rwPFS, and TTF were 8.90 months, 4.57 months, and 3.94 months, respectively. Overall ORR was 32.7%; it was 43.8% in the 226 patients with a target lesion. Regarding safety, the incidence of Grade ≥ 3 AEs was 48.4%. A total of 190/312 (60.9%) patients treated with T-DXd experienced dose reduction, interruption, or discontinuation of T-DXd treatment due to AEs. The most common reasons for dose reduction or interruption were neutrophil count decreased, anorexia, and malaise, while the most common reasons for discontinuation were interstitial pneumonia, anorexia, malaise, and nausea. Conclusions: This study demonstrates the effectiveness and safety of T-DXd in the 3L+ setting in real-world patients with HER2-positive gastric or gastroesophageal cancer. No new safety signals were identified on the basis of this study.

Role of immunotherapy in gastroesophageal cancer with liver metastasis: A meta-analysis of phase III randomized clinical trials.

319 Background: Recent studies have demonstrated a poor response to immunotherapy in patients with colorectal cancer with liver metastasis. The role of immune checkpoint inhibitors (ICIs) for patients with gastroesophageal (GE) cancer with liver metastasis remains unclear. Our objective was to investigate if ICIs are beneficial in patients with GE cancer with liver metastasis. Methods: We searched PubMed, Embase, ESMO, and ASCO Meeting Abstracts for phase III randomized clinical trials (RCTs) testing ICIs in metastatic/advanced GE cancer from 2017 to 2023. All phase III RCTs of metastatic GE cancer treated with ICIs that had available data on liver metastasis were analyzed. A meta-analysis was conducted on the survival outcomes (overall and progression-free survival), where hazard ratios were obtained, with 95% confidence intervals, using the standard random effects model. To assess the heterogeneity of the study outcomes, the I2 statistic was obtained. The I2 statistic represented the variability in the meta-analysis attributed to study heterogeneity. These analyses were applied to the overall cohort of studies, as well as within the liver metastasis (yes or no) sub-cohorts. All analyses were conducted in SAS v9.4 (Cary, NC) at a significance level of 0.05. Results: Seven Phase III RCTs were includedthat had available data on overall survival and/or progressive free survival in patients with liver metastasis. Of these, six were in the frontline setting and one in the later line. Overall, 6,109 patients were included. Overall survival was similar among all patients (HR 0.72 [0.67,0.77], p&lt;0.001, I2=0.0%), patients with no liver metastasis (HR 0.73 [0.67,0.81], p&lt;0.001, I2=0.0%), and patients with liver metastasis (HR 0.74 [0.67,0.81], p&lt;0.001, I2=0.0%), indicating that ICIs’ benefit on OS is consistent. Progression-free survival (PFS) was also similar among all patients (HR 0.63 [0.57,0.70], p&lt;0.001, I2=54.7%); those with no liver metastasis (HR 0.62 [0.51,0.76], p&lt;0.001, I2=62.3%), and with liver metastasis (HR 0.66 [0.57,0.76], p&lt;0.001, I2-0.0%). Funnel plots were used to identify a potential bias for studies included in the analysis and showed no significant sources of bias for OS and PFS. Conclusions: In this meta-analysis, ICIs were beneficial in patients with GE cancer with and without liver metastasis. However, the majority of the trials were in the frontline setting where ICIs were combined with chemotherapy. Further subgroup analyses should be performed with individual patient-level data to identify patients who respond best to ICIs.

The distribution of human epidermal growth factor receptor 2 (HER2) expression and the efficacy and safety of treatments in HER2-expressing advanced or metastatic gastroesophageal cancer: A systematic literature review (SLR).

405 Background: HER2 overexpression plays an important role in determining treatment options for patients with gastroesophageal cancer (GEC). HER2 overexpression has historically been defined dichotomously as HER2-positive (HER2+) or HER2-negative. An emerging potentially clinically relevant category is HER2-low, which could be targeted with HER2-directed antibody drug conjugates. However, data on the epidemiology and outcomes associated with HER2-low GEC are limited. Methods: An SLR of PubMed, Embase, and Cochrane Central Register of Controlled Trials databases was conducted to identify clinical trials, observational studies, and meta-analyses reporting clinical outcomes or distribution of HER2 expression by IHC and ISH in advanced or metastatic (a/m) GEC. Key inclusion criteria were: English language, published between 2013-2023, and sample size ≥100 HER2-expressing patients. HER2+ was defined as IHC score of 3+ or IHC 2+ and ISH+. HER2-low was defined as IHC 1+ or IHC 2+ and ISH-. Weighted averages were calculated for the proportion of patients who were HER2+ and HER2-low to estimate of the proportion of patients in each HER2 expression category. Results were categorized by patient population (all GEC or gastric cancer [GC] only). Results: Of 2,701 non-duplicated records screened, 174 studies met inclusion criteria. Distribution of HER2 expression was reported in 111 studies, 5 of which reported on the frequency of HER2 expression of IHC 1+ and/or IHC 2+ and ISH+. HER2 expression status varied by patient population, with a weighted average of 26.9% for HER2-low and 13.1-16.5% for HER2+ across groups (Table). Different cutoffs for HER2 amplification via ISH also affected the proportion of patients in each HER2 category across studies. Efficacy and safety outcomes were stratified by HER2 status or IHC results in 74 studies. However, only 3 observational studies reported outcomes separately for the HER2-low population, and results were inconclusive. Conclusions: The distribution of HER2 expression in a/m GEC in the identified studies is highly heterogenous, likely due to variability in IHC scoring and patient populations. Few studies with sufficient samples size (≥100 patients with HER2-expression a/mGEC) reported outcomes for HER2-low a/m GEC, and those that were identified were of low quality. The HER2-low a/m GEC population constitutes an unmet need for effective therapy. There is a need for consistent use of a standardized definition of HER2-low in a/mGEC and additional studies to better evaluate treatment options and outcomes for this patient population. [Table: see text]

Moving towards a personalised understanding of the nutritional impact of self-expanding metallic stents (SEMS) in gastro-oesophageal cancer: A retrospective case note review of a tertiary referral oncology centre.

301 Background: Dysphagia is a common life-impacting complication for patients with gastro-oesophageal (O-G) cancer. Options to alleviate dysphagia include insertion of SEMS or percutaneous endoscopic gastrostomy (PEG). SEMS improve quality of life by enabling a person to eat a varied diet, but are associated with complications including pain and need for reintervention. Although studies have shown SEMS improve dysphagia, consequent longitudinal impact on nutritional status has not been evaluated. There is a need to better characterise risks and benefits of SEMS to allow a personalised approach to both insertion and follow-up. Methods: We identified patients with a confirmed diagnosis of O-G cancer, who underwent SEMS insertion at The Christie NHS Foundation Trust in 2021 and 2022. Data was retrospectively collected about patient and stent characteristics, and patient outcomes to quantify benefits and risks of SEMS. Results: 112 patients had 127 SEMS inserted at The Christie. Patients’ International Dysphagia Diet Standardisation Initiative (IDDSI) score significantly improved after SEMS insertion (N=120); prior to SEMS 62% were only managing liquids and purees (IDDSI 3 and 4) and 24% were not able to eat enterally. Post SEMS, 76% tolerated textured foods (IDDSI 5 and above) and only 21.5% were limited to liquids/purees. We observed a significant reduction in the rate of weight loss (% body weight/10 days) following SEMS insertion (-0.010 ± 0.009 vs. -0.001 ± 0.010, P &lt; 0.001). 12% of patients experienced grade 3 SEMS-related toxicity or stent failure within 30 days, and 20% developed significant pain within 24 hours of SEMS insertion. Conclusions: SEMS provide meaningful nutritional benefit in the majority of patients with O-G cancer, as weight loss is significantly slowed following insertion. However, we identified two groups of patients who did not benefit from SEMS; those who continued to lose weight and those who had stent failure. We did not find predictive factors for stent failure from multivariate analysis of baseline demographics or stent characteristics. Therefore, more detailed analysis of tumour factors, imaging findings and SEMS location from a larger cohort of patients may be required to identify patients who are unlikely to benefit from SEMS, and alternative interventions such as PEG feeding could be considered.

Results from the phase 1b/2 SGNTUC-024 study: Assessment of tucatinib, trastuzumab, and FOLFOX for HER2+ GI cancers.

100 Background: HER2 is overexpressed in various GI tumors. Tucatinib (TUC), which is approved in combination with trastuzumab (Tras) in the US for previously treated RAS WT HER2+ metastatic colorectal cancer (mCRC), is a tyrosine kinase inhibitor highly selective for HER2. Preliminary safety and antitumor activity results of TUC + trastuzumab + FOLFOX in patients (pts) with HER2+ GI cancers are presented. Methods: The phase 1b/2 SGNTUC-024 (NCT04430738) study evaluated TUC + Tras + FOLFOX in pts with HER2+ metastatic GI cancers in Cohorts 1A, 1B, 1D (pts in Japan), and 2B. For Cohorts 1A, 1B, and 1D (enrolled sequentially), eligible pts had unresectable or metastatic HER2+ GI malignancies, including mCRC. Cohort 2B is still enrolling, and pts with HER2+ mCRC are eligible. Pts received a combination of TUC 150 mg orally twice a day (PO BID; Cohort 1A) or TUC 300 mg PO BID (Cohorts 1B, 1D, and 2B) + Tras + FOLFOX. Pts in Cohort 2B were enrolled to further assess the study regimen. Antidiarrheal prophylaxis was required for Cohort 1D. Results: As of July 10, 2023, 25 pts were treated (5, 11, 7, and 2 in Cohorts 1A, 1B, 1D, and 2B, respectively). In Cohort 1A (TUC 150 mg PO BID), the most common TEAEs were diarrhea, fatigue, nausea, and proteinuria (each in 60.0% [3/5]). For pts receiving TUC 300 mg PO BID, the most common TEAEs were diarrhea (90.0% [18/20]) and fatigue (65.0% [13/20]). Table 1 presents the overall summary of adverse events. In Cohort 1A, Treatment-emergent adverse events (TEAEs) leading to any treatment discontinuation were reported in 40.0% (2/5) pts, with 20.0% (1/5) discontinuing tucatinib. For pts treated with TUC 300 mg, TEAEs leading to treatment discontinuation were reported in 35.0% (7/20), with 15.0% (3/20) discontinuing tucatinib. One TEAE leading to death (aspiration) in Cohort 1A was unrelated to study treatment. Grade ≥3 diarrhea was observed in 45.5% (5/11) pts in Cohort 1B; most were observed in elderly pts or pts with gastric, gastroesophageal, or esophageal cancer or pts who were generally noncompliant with antidiarrheal treatment. No grade ≥3 diarrhea was observed in Cohort 1D. Among pts receiving TUC 300 mg, confirmed objective response rate was 83.3% (5/6) for mCRC, 40.0% (4/10) for gastroesophageal cancers, and 0% (0/4) for biliary tract cancer. Conclusions: TUC + Tras + FOLFOX showed manageable safety in the enrolled pt population and preliminary antitumor activity in pts with HER2+ mCRC and gastroesophageal cancer. This regimen will be compared with the standard of care (FOLFOX with or without bevacizumab/cetuximab) in the ongoing randomized, phase 3 study (MOUNTAINEER-03; NCT05253651) for pts with HER2+ RAS WT mCRC. Clinical trial information: NCT04430738 . [Table: see text]

Feasibility of functional evaluation in older adults with gastroesophageal cancer using fitness trackers.

298 Background: With advances in treatment and an aging population, gastroesophageal cancer (GEC) in older adults (OA) is increasing. Geriatric assessment (GA) is recommended as part of treatment decision in patients ≥ 65. Unfortunately, due to the complex nature and multiorgan effects of GEC, it is often difficult for oncologists to discern whether GA abnormalities are secondary to aging or the GEC itself. Because of their objectivity, fitness trackers are becoming increasingly popular in the functional evaluation of cancer patients. While fitness trackers have shown feasibility and validity in some cancers, data for their use in OA is currently limited. Objective: Evaluate the feasibility of functional status assessment via Fitbit activity tracker (FB) in comparison to traditional geriatric assessments in OA with GEC. Methods: Patients age ≥65 with any stage of GEC completed a GA and were given a FB to wear for 3 days in line with the battery life of the device. GA included a comprehensive evaluation of all geriatric domains with functional status assessed by performance status (PS), falls, Timed Up and Go (TUG), Activities of Daily Living (ADLs), and Instrumental Activities of Daily Living (IADLs). FB collected total steps per day (SPD), and patients’ mean SPD was calculated. We compared patient characteristics and outcomes using Fisher’s exact and Wilcoxon tests grouped by below and above median SPD. Results: 82 patients completed GA, of which 69 (84%) wore FB for ≥8 hours. Mean SPD for all patients was 2827 (38 – 11032), median SPD was 2264. Patients with ≤ median SPD were older (75 vs 72 p=0.034), female (32% vs 14% p=0.093), Black (24% vs 9% p=0.068), and living alone (29% vs 14% p=0.153). Patients SPD below and above the median had similar distributions of education level (≤12 yrs 35% vs 31% p=0.802) and Stage (&gt;2 82% vs 80% p=0.99). Patients with SPD below the median were more likely to have ≥ 2 abnormalities on GA (68% vs. 40%, p=0.03), self-reported PS &gt;2 (24% vs 0% p=0.013), and impaired IADL (33% vs 9% p=0.064). Patients with lower SPD had higher rates ≥Gr 3 toxicity (47% vs 20% p=0.022) and hospitalization (32% vs 6% p=0.006). The rate of abnormal TUG was similar in both groups (21% vs 17%, p=0.285). Conclusions: FB use for short objective evaluation functional status is feasible among OA with GEC and provides data which correlates with other GA abnormalities and treatment tolerance. Additional research is warranted to further incorporate this assessment tool into clinical care.

Unveiling proteomic diversity: A quantitative study of antibody drug conjugate and chemotherapy targets in gastroesophageal cancer.

261 Background: Gastroesophageal cancer (GEC), is a significant global health concern with a 5-year relative survival of 7% for metastatic GEC. Standard treatments often include surgery, chemotherapy, and radiation therapy, but their effectiveness can be limited. Chemotherapy is frequently utilized in the treatment of GEC, although no biomarkers for chemotherapy are used in the selection of the chemo agent. There are several well-known biomarkers of resistance and sensitivity for various chemo agents. We used targeted proteomics to quantify protein expression levels of several protein biomarkers associated with chemotherapy efficiency in 125 GEC patients. These include resistance markers for platinum agents (ERCC1), and tubulin inhibitors (TUBB3). It also includes sensitivity markers for irinotecan/topotecan (Topo1), and doxorubicin/etoposide (Topo2A). We also assessed the protein levels of several antibodies-drug conjugate markers (EGFR, Her2, Trop2, FR-alpha, Mesothelin, Axl, CLDN18.2, and Nectin-4). Methods: FFPE tumor tissues from 125 clinical GC patients were microdissected and solubilized for mass spectrometry-based targeted proteomic analysis in our CLIA-certified laboratory. 72 proteins were quantified from 2-3 sections of FFPE tissue. Results: 5-Fluorouracil (5-FU), taxanes, and platinum agents (such as carboplatin) are among the chemotherapy agents that are frequently used to treat GEC. TYMP, a sensitivity marker for 5-FU, was expressed in 32% of GEC cases. ERCC1, a resistance marker for platinum drugs, was expressed at 34%. Additionally, 48% of GEC exhibited TUBB3, a resistance marker for paclitaxel and docetaxel. Topoisomerase 1 (Topo1) is the target for irinotecan or topotecan, and is also the target for some ADCs (e.g. trastuzumab deruxtecan, sacituzumab govitecan etc.). Topo1 was expressed in 92% of GEC with a 10x range (415 - 4195 amol/μg). Another topoisomerase, Topo2A, targetable by etoposide, epirubicin, and doxorubicin, was expressed in 59% of GEC with 19x range (402-7804 amol/μg). ADC targets, such as EGFR (82% detected with 184x range of distribution), Her3 (18%, 4x), AXL (18%,7x), MET (27%, 19x), and Trop2 (50%, 57x) showed a wide range of protein expression. With a 56x range (318 - 17786 amol/μg), Her2 was found in 46% of GEC, of which 12% of GEC had overexpression of Her2 (&gt;740 amol/μg), suggesting that the majority of GEC has low levels of Her2 (318-690 amol/μg), which is potentially targetable by newer anti-Her2 agents. Conclusions: Every cancer is different, and the ability to quantitate simultaneously 72 protein biomarkers from 2-3 FFPE sections provides a wealth of actionable information that, when combined with other multi-omics biomarker data, will help guide clinical treatment or patient stratification for clinical trials.

Does routine clinical assessment of older adults with gastroesophageal cancer tell the whole story?

297 Background: Geriatric Assessment (GA) can help oncologists determine fitness of their older patients (pt) for anti-cancer therapy. Our objective was to compare routine provider assessment (PA) and GA of older adults with gastroesophageal cancer (GEC). Methods: Patients ≥65 with any stage of GEC completed a GA. The pt’s provider completed a PA and abnormalities detected by both assessments were centrally reviewed and compared. GA and PA assessed functional status, nutrition, comorbidities, psychological distress, cognition, social support, and chemotherapy toxicity risk. Validated assessment tools were used for the GA. Data collected 3 months post-enrollment included hospitalization, ≥ grade 3 toxicities, and treatment delays. We compared the proportions detected/not detected abnormalities by PA vs GA using McNemar’s test for paired data, and we measured agreement using Kappa statistics (1=full, 0=no, -1=disagreement). Results: 82 pts were enrolled, majority male (74%), median age 73 (65-91), stage III/IV (82%) disease on first line therapy (79%). Cancer sites included gastric (32%), esophageal (43%), GEJ (26%). Pts’ demographic and clinical characteristics did not predict for the identification of GA abnormalities. GA detected 196 abnormalities and PA detected 86. Majority of pts (84%) had ≥ 1 unidentified abnormality by PA. Providers identified more pts with clinically significant comorbidities as compared to GA. However, the GA identified more abnormalities compared to PA in all other evaluated domains (Table). Low agreement was found between PA and GA in any of the domains. Pts scoring high on the CARG chemotherapy toxicity prediction tool (p=0.004) and pts with evidence of psychological distress (p=0.049) had more ≥ grade 3 toxicity. Pts with abnormalities in functional status, nutrition, psychological distress, and a high CARG score were more likely to be hospitalized during therapy. Conclusions: Clinical characteristics of older pts with GEC are not predictive of GA abnormalities. While providers were better at identifying comorbidities, the GA resulted in a comprehensive evaluation of all domains and identified significant abnormalities that affect treatment outcomes in this population. [Table: see text]

First-line pembrolizumab (pembro) plus chemotherapy (chemo) for advanced gastroesophageal junction cancer (GEJC) and esophageal adenocarcinoma (EAC): Analysis of KEYNOTE-590 and KEYNOTE-859 by tumor type.

345 Background: First-line (1L) treatment of GEJC and EAC is similar to that for gastric adenocarcinomas, based on evidence from 2 large phase 3 gastric and esophageal cancer trials. The phase 3 KEYNOTE-590 trial (NCT03189719) showed 1L pembro + chemo significantly improved OS and PFS in pts with esophageal cancer. The phase 3 KEYNOTE-859 trial (NCT03675737) showed 1L pembro + chemo significantly improved OS, PFS, and ORR in pts with HER2-negative gastric cancer or GEJC. This post hoc, exploratory analysis was conducted to examine the efficacy of 1L pembro + chemo in the GEJC and EAC subgroups of KEYNOTE-590 and the GEJ subgroup of KEYNOTE-859. Methods: Pts with untreated advanced EAC or Siewert type 1 adenocarcinoma of the GEJ (KEYNOTE-590) or HER2-negative GEJ adenocarcinoma (KEYNOTE-859), measurable disease per RECIST v1.1, and ECOG PS 0 or 1 were evaluated. In both studies, pts were randomly assigned 1:1 to receive pembro 200 mg IV or pbo every 3 wk (Q3W) for ≤35 cycles, each with chemo (5-fluorouracil + cisplatin [FP] in KEYNOTE-590; FP or capecitabine + oxaliplatin in KEYNOTE-859). Efficacy end points for this analysis were OS and PFS (per RECIST v1.1 by blinded independent central review) by tumor subtype. Database cutoff was July 2, 2020, for KEYNOTE-590 and July 1, 2022, for KEYNOTE-859. Results: Overall, 201 pts from KEYNOTE-590 (n=99 pembro + chemo; n=102 pbo + chemo) with GEJC or EAC and 334 pts from KEYNOTE-859 (n=149 pembro + chemo; n=185 pbo + chemo) with GEJC were included. In KEYNOTE-590, 91 pts had GEJC only (n=41 pembro + chemo; n=50 pbo + chemo) and 169 (n=82 pembro + chemo; n=87 pbo + chemo) had GEJC + EAC + CPS ≥1. In KEYNOTE-859, 287 pts (n=123 pembro + chemo; n=164 pbo + chemo) had GEJC + CPS ≥1. Demographic and baseline characteristics were well balanced. Median time from randomization to database cutoff for pts with GEJC and EAC was 23.5 mo (range, 15.3-33.6) in KEYNOTE-590 and 25.8 mo (range, 12.4-43.0) in KEYNOTE-859. Efficacy outcomes by tumor type are shown in the Table. Conclusions: Consistent with results from the ITT populations of KEYNOTE-590 and KEYNOTE-859, 1L pembro + chemo provided clinically meaningful improvement in OS and PFS vs chemo in pts with untreated advanced GEJC and EAC. These data support the use of 1L pembro + chemo for pts with advanced GEJC and EAC. Clinical trial information: NCT03189719 and NCT03675737 . Efficacy by tumor type and CPS (pembro vs pbo). KEYNOTE-590 GEJC n=91 KEYNOTE-859 GEJC n=334 KEYNOTE-590 GEJC + EAC n=201 KEYNOTE-590 GEJC + EAC + CPS ≥1 n=169 KEYNOTE-859GEJC + CPS ≥1 n=287 OS, median, mo 12.7 vs 10.0 14.2 vs 12.0 11.6 vs 9.9 13.0 vs 10.1 14.2 vs 12.1 OS HR (95% CI) 0.73 (0.45-1.17) 0.74 (0.58-0.94) 0.75 (0.55-1.03) 0.73 (0.51-1.03) 0.71 (0.55-0.93) PFS, median, mo 6.3 vs 6.1 6.8 vs 5.7 8.0 vs 5.7 8.0 vs 5.7 6.8 vs 5.6 PFS HR (95% CI) 0.65 (0.39-1.08) 0.78 (0.61-1.01) 0.56 (0.40-0.78) 0.55 (0.38-0.79) 0.76 (0.58-1.00

Epidemiological characteristics of gastric and pancreatic cancers in Latin America: The LACOG 0222 GASPAR study.

TPS710 Background: Gastric and pancreatic tumors remain among the cancers with the poorest prognoses in both high and low/middle-income countries. Data on the clinicopathological characteristics, standard treatments, and outcomes of these tumors are scarce in Latin America. This study is the first comprehensive effort to report epidemiological and clinical data in this region. Methods: The LACOG 0222 GASPAR trial ( NCT05924789 ) is a retrospective and prospective (bidirectional) observational cohort study. Enrollment of 200 patients across 15 sites in Latin America is planned, 120 patients in cohort A (gastric cancer) and 80 patients in cohort B (pancreatic cancer). No interventions are proposed. Eligibility criteria include age ≥18 years, histological diagnosis of gastric and gastroesophageal junction cancer (cohort A) or pancreatic cancer (cohort B), advanced disease diagnosis since January 2019, and availability of adequate medical data for data collection. The primary objective is to describe the clinical characteristics, treatment patterns, and outcomes of patients with gastric and pancreatic cancer in Latin America. Data on patients’ clinical characteristics, demographics, tumor pathological features, surgical therapy, radiotherapy, chemotherapy, and target therapy will be collected. Patient outcomes, such as recurrence-free survival, progression-free survival, and overall survival will also be collected. Patients will be followed up for up to 3 years after diagnosis. No a priori sample-size calculations were performed. The demographic and underlying disease characteristics will be evaluated using descriptive statistics. Time-to-event outcomes (disease-free survival, progression-free survival, and overall survival) will be estimated using the Kaplan-Meier method. From August 2023 to September 2023, 34 pts were included. The target accrual is expected to be completed by February 2024. The results are expected to be presented in August 2024.

Real-world treatment patterns, testing patterns, and clinical outcomes of first-line (1L) therapy for metastatic gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma (mGC/GEJC/EAC).

275 Background: GC/GEJC/EAC are among the leading causes of cancer-related morbidity and mortality worldwide. Nivolumab + fluoropyrimidine- + platinum-containing chemotherapy (NIVO+chemo) has demonstrated superior efficacy in patients with advanced non-HER2-positive (HER2-) GC/GEJC/EAC versus chemo alone in the CheckMate 649 trial. The objective of this study was to characterize real-world treatment and PD-L1 testing patterns in the 1L setting for mGC/GEJC/EAC since the FDA approval of NIVO+chemo on April 16, 2021. Methods: This retrospective observational study used the electronic medical record data from the ConcertAI Patient360 database. Adult patients with HER2- mGC/GEJC/EAC and 1L initiation date (index date) between April 16, 2021 and October 31, 2022 were included. PD-L1 testing patterns and 1L regimens were described overall and stratified by PD-L1 testing. The analyses of clinical outcomes are currently ongoing. Results: A total of 161 patients with mGC/GEJC/EAC met the inclusion criteria. The median age at index was 67.0 years, 76.4% were male, and the median follow-up time from index date was 6.7 months. 81 (50.3%) patients had evidence of receiving at least one PD-L1 test (median [interquartile range] time from first test to 1L initiation: 0.4 [-0.1, 1.0] months) among whom 28 (34.6%) had the first test documented after 1L initiation. Overall, 1L immunotherapy-based regimens were received by 63 (39.1%) patients, with NIVO+chemo being the most common (n = 47; 29.2%). 1L fluoropyrimidine- + platinum-containing chemotherapy and other chemotherapies were received by 51 (31.7%) and 42 (26.1%) patients, respectively. Among patients with evidence of PD-L1 testing, 31 (38.3%) received NIVO+chemo, and 37 (45.7%) received chemotherapy alone. Among those without evidence of PD-L1 testing, 56 (70.0%) received chemotherapy alone, and 16 (20.0%) received NIVO+chemo. Conclusions: These preliminary findings show an early uptake of NIVO+chemo in the advanced or metastatic GC/GEJC/EAC patient population. With a majority of PD-L1 untested patients receiving chemotherapy only as 1L therapy, there is an opportunity for these patients to potentially benefit from immuno-oncology containing regimens. Further analyses are needed to characterize the chemotherapy only treated patient population.

Real world prevalence of biomarkers for treatment of advanced gastric cancer or gastroesophageal junction cancer in a cohort of Colombian patients.

402 Background: Gastric cancer (GC) is the leading cause of cancer-related deaths in Colombia, GLOBOCAN estimated 6.451 deaths in 2022. Development of immune checkpoint inhibitors and HER2 target therapy with chemotherapy had improved overall survival in advanced setting, but we do not have data about the prevalence of biomarkers used for selection of these patients in Colombia or Latin-America. Our aim is to describe the prevalence of biomarkers used currently for selection of treatment in a real-world multicenter cohort of advanced gastric and gastroesophageal junction (GEJ) cancer. Methods: We did a retrospective observational multicenter study of patients with advanced GC/GEJ cancer treated at three reference cancer centers in Bogota, Colombia between January 1, 2023 and July 31, 2023. We reviewed medical history and pathology reports looking for the prevalence of biomarkers used for selection of first line systemic therapy. Ventana 4B5 for HER2 IHQ evaluation and Dako 22C3 for PDL1 expression by CPS were used. MMR proteins were evaluated by IHQ nuclear expression. Results: 101 patients with advanced GC/GEJ were included. The median age was 61 years (range 18-83), 53,5% of patients were men, 92.1% were gastric cancer and 87,1% were de novo stage IV. Signet ring cells were found in 40%, peritoneal carcinomatosis was documented in 59% and 75,2% were distal tumors (no cardias or GEJ involvement). PDL1 positivity, defined as CPS ≥1 was found in 30.6%, using CPS ≥ 5 cutoff just 22.7% of them were positive. HER2 positivity and MMR deficiency were found in the same proportion of patients 5%. Among young patients (&lt; 50 years) 80% had diffuse histology, 30% were CPS ≥5. HER2 status and PDL1 testing was unknown in 21% and 29% respectively. Conclusions: Among these real-world patients, both HER2 and PDL1 positivity was lower than reported in other regions. Higher incidence of distal tumors, signet ring cells and diffuse histology could explain this difference. Correlation of PDL1 positivity between 22C3 and 28.8 was unknown in our population. Our study remarks the high medical need for investigation of biomarkers and developing of prospective studies for correlation and other targets like Claudins and FGFR2b.[Table: see text]