Real‑world challenge for clinicians treating advanced gastroesophageal adenocarcinoma (Review)

Baxter, Mark; Petty, Russell; Swinson, Daniel; Hall, Peter; O’Hanlon, Shane

doi:10.3892/ijo.2021.5202

Cited by 7 publications

(8 citation statements)

References 81 publications

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“…Durable antitumor efficacy in patients with heavily pretreated, advanced disease is often limited 16–20 . Furthermore, these patients frequently present with a high symptom burden and medical comorbidities that introduce challenges in achieving antitumor efficacy while managing patient quality of life 21 . Traditional chemotherapy treatments have focused on disease control and palliation of symptoms 16–21 .…”

Section: Discussionmentioning

confidence: 99%

“…21 Traditional chemotherapy treatments have focused on disease control and palliation of symptoms. [16][17][18][19][20][21] In this study, the efficacy response to targeted zolbetuximab monotherapy was limited: 2 patients had SD lasting >6 months.…”

Section: Discussionmentioning

confidence: 99%

“… 16 , 17 , 18 , 19 , 20 Furthermore, these patients frequently present with a high symptom burden and medical comorbidities that introduce challenges in achieving antitumor efficacy while managing patient quality of life. 21 Traditional chemotherapy treatments have focused on disease control and palliation of symptoms. 16 , 17 , 18 , 19 , 20 , 21 In this study, the efficacy response to targeted zolbetuximab monotherapy was limited: 2 patients had SD lasting >6 months.…”

Section: Discussionmentioning

confidence: 99%

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Phase 1 trial of zolbetuximab in Japanese patients with CLDN18.2+ gastric or gastroesophageal junction adenocarcinoma

et al. 2022

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Zolbetuximab is a chimeric monoclonal antibody that targets claudin‐18.2, a candidate biomarker in patients with advanced gastric/gastroesophageal cancer. This nonrandomized phase 1 study (NCT03528629) enrolled previously treated Japanese patients with claudin‐18.2–positive locally advanced/metastatic gastric/gastroesophageal cancer in two parts: Safety (Arms A and B, n = 3 each) and Expansion (n = 12). Patients received intravenous zolbetuximab 800 mg/m2 on cycle 1, day 1 followed by 600 mg/m2 every 3 weeks (Q3W; Safety Part Arm A and Expansion) or 1000 mg/m2 Q3W (Safety Part Arm B). For the Safety Part, the primary endpoint was safety (i.e., dose‐limiting toxicities [DLTs]) and a secondary endpoint was objective response rate (ORR) by investigator. For the Expansion Part, the primary endpoint was ORR by investigator and secondary endpoints included ORR by central review and safety. Additional secondary endpoints for both the Safety and Expansion Parts were disease control rate (DCR), overall survival (OS), progression‐free survival (PFS), duration of response, pharmacokinetics, and immunogenicity. In 18 patients, no DLTs (Safety Part) or drug‐related treatment‐emergent adverse events (TEAEs) grade ≥3 were observed. Most TEAEs were gastrointestinal. In 17 patients with measurable lesions, best overall response was stable disease (64.7%) or progressive disease (35.3%). The DCR was 64.7% (95% confidence interval 38.3–85.8). In Arm A and Expansion combined (n = 15), median OS was 4.4 months (2.6–11.4) and median PFS was 2.6 months (0.9–2.8). In Arm B (n = 3), median OS was 6.4 months (2.9–6.8) and median PFS was 1.7 months (1.2–2.1). Zolbetuximab exhibited no new safety signals with limited single‐agent activity in Japanese patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Phase 1 trial of zolbetuximab in Japanese patients with CLDN18.2+ gastric or gastroesophageal junction adenocarcinoma

et al. 2022

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“…BMI was found to be a less valid screening tool for determining malnutrition in elderly patients with cancer (22).In addition, the use of individualized nutritional support is recommended in elderly patients with cancer who are already malnourished or are at a risk of becoming malnourished (23). These patients are predisposed to age-related sarcopenia and reduced gastrointestinal absorption (24).…”

Section: Discussionmentioning

confidence: 99%

Prevalence and Prognostic Value of Malnutrition Among Elderly Cancer Patients Using Three Scoring Systems

et al. 2021

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Background: Malnutrition is common in patients with cancer and is associated with adverse outcomes, but few data exist in elderly patients. The aim of this study was to report the prevalence of malnutrition using three different scoring systems and to examine the possible clinical relationship and prognostic consequence of malnutrition in elderly patients with cancer.Methods: Nutritional status was assessed by using controlling nutritional status (CONUT), the prognostic nutritional index (PNI), and the nutritional risk index (NRI). Quality-of-life (Qol) was assessed during admission by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30. Performance status (PS) was assessed by using the Eastern Cooperative Oncology Group (ECOG) classification. The relationship between nutritional status and overall survival and Qol were examined.Results: Data were available for 1,494 elderly patients with cancer (63.65% male), the mean age was 70.76 years. According to the CONUT, NRI, and PNI, 55.02, 58.70, and 11.65% patients were diagnosed with malnutrition, respectively. Worse nutritional status was related to older, lower BMI, lower hand grip strength, and more advanced tumor stage. All malnutrition indexes were correlated with each other (CONUT vs. PNI, r = −0.657; CONUT vs. NRI scores, r = −0.672; PNI vs. NRI scores, r = 0.716, all P < 0.001). During a median follow-up of 43.1 months, 692 (46.32%) patients died. For patients malnourished, the incidence rate (events-per-1,000person-years) was as follows: CONUT (254.18), PNI (429.91), and NRI (261.87). Malnutrition was associated with increased risk for all-cause mortality (adjust HR [95%CI] for CONUT: 1.09 [1.05–1.13], P < 0.001; PNI: 0.98[0.97–0.99], P < 0.001; NRI: 0.98 [0.98–0.99], P < 0.001). All malnutrition indexes improved the predictive ability of the TNM classification system for all-cause mortality. Deterioration of nutritional status was associated with deterioration in Qol parameters and immunotherapeutic response (P < 0.001).Conclusions: Malnutrition was prevalent in elderly patients with cancer, regardless of the assessment tools used, and associated with lower Qol and the immunotherapy response.

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“…However, elderly patients with frailty or multimorbidity who are vulnerable to the adverse effects of chemotherapy are often excluded from randomised controlled trials because of restrictive eligibility criteria [ 8 – 11 ]. The proportions of patients aged 70 years or older were 17% in the SPIRITS trial [ 4 ] and 31% in the G-SOX trial [ 5 ], which were much lower than the overall proportion of elderly patients with gastric cancer in Japan [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Oxaliplatin- versus cisplatin-based regimens for elderly individuals with advanced gastric cancer: a retrospective cohort study

et al. 2022

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Background Whether an oxaliplatin- or cisplatin-based regimen is more optimal for treating elderly patients with advanced gastric cancer, in terms of survival and adverse events remains unclear. Methods In this retrospective cohort study, we used stacked claim data of residents in two Japanese prefectures collected between 2012 and 2017 and between 2014 and 2019, respectively. We included patients with advanced gastric cancer who received oxaliplatin-based and cisplatin-based regimens. Propensity score overlap weighting analysis was conducted to compare overall survival and granulocyte colony-stimulating factor use during chemotherapy between the oxaliplatin- and cisplatin-based treatment groups. Results A total of 242 patients were included in the study. After propensity score weighting, Kaplan–Meier analysis showed no significant differences in overall survival between the two groups (hazard ratio: 1.13; 95% confidence interval, 0.60–2.11; p = 0.70). However, the proportion of patients receiving granulocyte colony-stimulating factor was significantly lower in the oxaliplatin group than in the cisplatin group (2.3% vs.22.7%, p = 0.01). Conclusions Survival did not differ significantly between elderly patients with advanced gastric cancer treated with oxaliplatin-based versus cisplatin-based regimens; however, the oxaliplatin-based regimen was associated with less granulocyte colony-stimulating factor use.

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Real‑world challenge for clinicians treating advanced gastroesophageal adenocarcinoma (Review)

Cited by 7 publications

References 81 publications

Phase 1 trial of zolbetuximab in Japanese patients with CLDN18.2+ gastric or gastroesophageal junction adenocarcinoma

Phase 1 trial of zolbetuximab in Japanese patients with CLDN18.2+ gastric or gastroesophageal junction adenocarcinoma

Prevalence and Prognostic Value of Malnutrition Among Elderly Cancer Patients Using Three Scoring Systems

Oxaliplatin- versus cisplatin-based regimens for elderly individuals with advanced gastric cancer: a retrospective cohort study

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