Podcast
Questions and Answers
What is the minimum age requirement for eligible patients in the study?
What is the minimum age requirement for eligible patients in the study?
- 16 years
- 18 years (correct)
- 21 years
- 25 years
What percentage of tumor cells must show CLDN18 staining for a patient to be eligible?
What percentage of tumor cells must show CLDN18 staining for a patient to be eligible?
- 90%
- 60%
- 50%
- 75% (correct)
What statistical method was implemented to estimate the distribution of progression-free survival?
What statistical method was implemented to estimate the distribution of progression-free survival?
- Kaplan-Meier method (correct)
- Chi-square test
- Stratified log-rank test
- Cox proportional hazard model
What is the primary endpoint of the study?
What is the primary endpoint of the study?
Which factor was included in the stratification of the Cox proportional hazard model?
Which factor was included in the stratification of the Cox proportional hazard model?
How were patients assigned to treatment groups?
How were patients assigned to treatment groups?
What was the primary endpoint addressed in the ongoing survey study?
What was the primary endpoint addressed in the ongoing survey study?
What was the loading dose of zolbetuximab administered to the patients?
What was the loading dose of zolbetuximab administered to the patients?
What criteria were used to assess radiologically evaluable disease?
What criteria were used to assess radiologically evaluable disease?
How many patients were initially assessed for eligibility in the study?
How many patients were initially assessed for eligibility in the study?
What does CLDN18.2-negative imply in the context of the patient selection?
What does CLDN18.2-negative imply in the context of the patient selection?
What type of cancer were the eligible patients diagnosed with?
What type of cancer were the eligible patients diagnosed with?
Which statistical measure quantifies the hazard associated with certain covariates in the study?
Which statistical measure quantifies the hazard associated with certain covariates in the study?
Which performance status score is required for patient eligibility in the study?
Which performance status score is required for patient eligibility in the study?
What was the subsequent publication expected to disclose?
What was the subsequent publication expected to disclose?
What criteria were used for excluding potential participants from the study?
What criteria were used for excluding potential participants from the study?
What was the planned number of events required for the final analysis of progression-free survival?
What was the planned number of events required for the final analysis of progression-free survival?
What is the assumed median progression-free survival for the treated group?
What is the assumed median progression-free survival for the treated group?
What significance level was used for the overall analysis?
What significance level was used for the overall analysis?
What was the dropout rate considered in the sample size calculation?
What was the dropout rate considered in the sample size calculation?
Which group had the highest number of adverse events leading to discontinuation?
Which group had the highest number of adverse events leading to discontinuation?
What was the threshold for the one-sided type I error rate in the study?
What was the threshold for the one-sided type I error rate in the study?
What was the planned number of deaths for the final analysis of overall survival?
What was the planned number of deaths for the final analysis of overall survival?
How many patients were included in the efficacy analysis for the zolbetuximab group?
How many patients were included in the efficacy analysis for the zolbetuximab group?
What condition was required to test overall survival after the progression-free survival analysis?
What condition was required to test overall survival after the progression-free survival analysis?
Which of the following represents the modified regimen mentioned in the analysis?
Which of the following represents the modified regimen mentioned in the analysis?
Which of the following was NOT a reason for patient discontinuation in the study?
Which of the following was NOT a reason for patient discontinuation in the study?
What was the significance of the HR value of 0.80 in the analysis?
What was the significance of the HR value of 0.80 in the analysis?
Which acronym refers to patients' performance status scoring in the study?
Which acronym refers to patients' performance status scoring in the study?
What percentage of patients in the zolbetuximab group showed an objective response?
What percentage of patients in the zolbetuximab group showed an objective response?
How does the median duration of response compare between the zolbetuximab and placebo groups?
How does the median duration of response compare between the zolbetuximab and placebo groups?
What was the median duration of response for the placebo group?
What was the median duration of response for the placebo group?
How many patients in the zolbetuximab group received subsequent anticancer therapies?
How many patients in the zolbetuximab group received subsequent anticancer therapies?
What was the objective response observed in patients with measurable disease in the zolbetuximab group?
What was the objective response observed in patients with measurable disease in the zolbetuximab group?
What is the median duration of exposure in the zolbetuximab group?
What is the median duration of exposure in the zolbetuximab group?
What was the median duration of response for patients who received placebo with measurable disease?
What was the median duration of response for patients who received placebo with measurable disease?
What was the statistical confidence interval (CI) for the objective response rate in the zolbetuximab group?
What was the statistical confidence interval (CI) for the objective response rate in the zolbetuximab group?
What percentage of patients in the zolbetuximab plus mFOLFOX6 group experienced nausea?
What percentage of patients in the zolbetuximab plus mFOLFOX6 group experienced nausea?
Which treatment-emergent event had the highest percentage in the placebo plus mFOLFOX6 group?
Which treatment-emergent event had the highest percentage in the placebo plus mFOLFOX6 group?
What is the rate of treatment-emergent serious events in the zolbetuximab group?
What is the rate of treatment-emergent serious events in the zolbetuximab group?
Which treatment-emergent event led to discontinuation of study drugs for 106 patients in the zolbetuximab group?
Which treatment-emergent event led to discontinuation of study drugs for 106 patients in the zolbetuximab group?
What was the percentage of patients in the placebo group who discontinued treatment due to treatment-related events?
What was the percentage of patients in the placebo group who discontinued treatment due to treatment-related events?
What was the most common treatment-emergent event leading to death in the placebo group?
What was the most common treatment-emergent event leading to death in the placebo group?
In terms of grade ≥3 treatment-emergent events, what was the percentage of patients affected in the zolbetuximab group?
In terms of grade ≥3 treatment-emergent events, what was the percentage of patients affected in the zolbetuximab group?
What percentage of patients in the zolbetuximab group experienced treatment-related adverse events leading to discontinuation of the drug?
What percentage of patients in the zolbetuximab group experienced treatment-related adverse events leading to discontinuation of the drug?
What was the rate of treatment-emergent events leading to death in the zolbetuximab group?
What was the rate of treatment-emergent events leading to death in the zolbetuximab group?
Which event had the highest grade ≥3 occurrence in the zolbetuximab group?
Which event had the highest grade ≥3 occurrence in the zolbetuximab group?
Which event affected 78 patients in the zolbetuximab group at all grades?
Which event affected 78 patients in the zolbetuximab group at all grades?
What was the percentage of patients experiencing peripheral sensory neuropathy in the placebo group?
What was the percentage of patients experiencing peripheral sensory neuropathy in the placebo group?
What percentage of patients experienced treatment-emergent fatigue in the placebo group?
What percentage of patients experienced treatment-emergent fatigue in the placebo group?
Which treatment-related event led to discontinuation in the lowest percentage of patients in the placebo group?
Which treatment-related event led to discontinuation in the lowest percentage of patients in the placebo group?
Flashcards
Eligible patient age
Eligible patient age
Patients must be 18 years or older.
CLDN18.2 positivity
CLDN18.2 positivity
At least 75% of tumor cells must show moderate-to-strong CLDN18 membranous staining.
HER2 negativity
HER2 negativity
Patients cannot have HER2.
Treatment type
Treatment type
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Primary Endpoint
Primary Endpoint
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Randomized assignment
Randomized assignment
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Study Registration
Study Registration
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Study Status
Study Status
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Discontinued Treatment Count
Discontinued Treatment Count
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Disease Progression
Disease Progression
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Adverse Event Count
Adverse Event Count
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Progression-Free Survival
Progression-Free Survival
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Statistical Power (93%)
Statistical Power (93%)
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Adverse Event
Adverse Event
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Hypothesis Testing
Hypothesis Testing
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Overall Survival
Overall Survival
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Kaplan-Meier Method
Kaplan-Meier Method
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Log-Rank Test
Log-Rank Test
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Eligibility Assessment
Eligibility Assessment
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Progression-free survival analysis boundary
Progression-free survival analysis boundary
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One-sided type I error rate
One-sided type I error rate
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Overall survival testing
Overall survival testing
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Interim overall survival analysis
Interim overall survival analysis
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Final overall survival analysis
Final overall survival analysis
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81% power to detect difference
81% power to detect difference
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CLDN18.2-positive tumors
CLDN18.2-positive tumors
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mFOLFOX6 regimen
mFOLFOX6 regimen
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Zolbetuximab group
Zolbetuximab group
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Placebo group
Placebo group
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Objective response to cancer treatment
Objective response to cancer treatment
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Median duration of response (months)
Median duration of response (months)
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Hazard ratio (HR)
Hazard ratio (HR)
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Subgroup analysis
Subgroup analysis
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Sensitivity analysis
Sensitivity analysis
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What does the study investigate?
What does the study investigate?
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Treatment groups in the study
Treatment groups in the study
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mFOLFOX6
mFOLFOX6
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Zolbetuximab
Zolbetuximab
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Treatment-Emergent Events
Treatment-Emergent Events
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Grade ≥3
Grade ≥3
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Treatment-Emergent Serious Events
Treatment-Emergent Serious Events
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Discontinuation of study drug
Discontinuation of study drug
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Treatment-Related Events
Treatment-Related Events
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Treatment-Emergent Events Leading to Death
Treatment-Emergent Events Leading to Death
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Treatment-Related Events Leading to Death
Treatment-Related Events Leading to Death
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Nausea
Nausea
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Vomiting
Vomiting
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Peripheral Sensory Neuropathy
Peripheral Sensory Neuropathy
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Neutropenia
Neutropenia
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Study Notes
Zolbetuximab plus mFOLFOX6 Trial
- Study Type: Multicentre, randomised, double-blind, phase 3 trial
- Purpose: Investigated efficacy and safety of zolbetuximab (targets CLDN18.2) plus mFOLFOX6 (chemotherapy) versus placebo plus mFOLFOX6 in CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma.
- Patient Eligibility: Aged 18 or older, CLDN18.2-positive (75% or more tumour cells showing moderate-to-strong CLDN18 staining), HER2-negative, previously untreated, locally advanced unresectable or metastatic adenocarcinoma, radiologically evaluable disease (measurable or non-measurable), ECOG performance status 0 or 1, and adequate organ function.
- Randomisation: 1:1 ratio, stratified by region, number of organs with metastases, and prior gastrectomy.
Study Findings
- Participants: 565 patients, 283 in zolbetuximab group, 282 in placebo group.
- Follow-up: Median 12.94 months (zolbetuximab) and 12.65 months (placebo).
- Progression-Free Survival: Zolbetuximab significantly reduced the risk of disease progression or death (HR 0.75, 95% CI 0.60-0.94; p=0.0066). Median progression-free survival: 10.61 months (zolbetuximab) vs 8.67 months (placebo).
- Overall Survival: Zolbetuximab significantly reduced the risk of death (HR 0.75, 95% CI 0.60-0.94; p=0.0053). Median overall survival: 18.23 months (zolbetuximab) vs. 15.54 months (placebo).
- Adverse Events: Grade 3 or worse treatment-emergent adverse events occurred in 242 (87%) of 279 patients in the zolbetuximab group versus 216 (78%) of 278 patients in the placebo group; most frequent were nausea, vomiting, and decreased appetite. Treatment-related deaths: 5 (2%) in zolbetuximab group versus 4 (1%) in placebo group.
Interpretation
- Zolbetuximab significantly prolonged progression-free survival and overall survival when combined with mFOLFOX6 compared to placebo plus mFOLFOX6.
- Zolbetuximab might represent a new first-line treatment for CLDN18.2-positive, HER2-negative gastric or gastro-oesophageal junction adenocarcinoma.
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Description
This quiz delves into a phase 3 trial investigating the efficacy and safety of zolbetuximab in combination with mFOLFOX6 for treating CLDN18.2-positive gastric adenocarcinoma. Participants included patients who were HER2-negative, previously untreated, and met specific eligibility criteria. Test your knowledge on study design, patient demographics, and key findings from this significant clinical trial.
