TriangleNCT03052608 · OUTCOME
Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR) Assessment
Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.
- Measure
- MEDIAN
- Unit
- Months
- Interval / dispersion
- 95% Confidence Interval
- Time frame
- From time of Study Start up to 33 months
What was measured
PFS was defined as the time from randomization to the date of the first documentation of progressive disease as assessed by the independent radiologist or death due to any cause, whichever occurred first. PFS (in months) was calculated as (date of event or censoring-randomization+1)/30.4375. Progressive disease is defined per RECIST version 1.1, as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of 1 or more new lesions.
Analysis population: The full analysis (FA) population included all participants who were randomized, and participants were classified according to the treatment assigned at randomization.
Groups in this outcome
Lorlatinib
Lorlatinib monotherapy at the recommended Phase 2 dose of 100 mg, was administered orally once daily (QD) at approximately the same time of the day on a continuous daily dosing schedule. Each treatment cycle was defined as 28 days. Treatment continued until confirmation of RECIST version 1.1 defined disease progression assessed by the blinded independent central review (unless clinical benefit was still achievable), participant refusal, participant lost to follow-up, unacceptable toxicity, death, or the study was terminated by the sponsor, whichever occurred first.
Crizotinib
Crizotinib monotherapy at the registered dose of 250 mg, was administered orally twice daily (BID) at approximately the same time in the morning and evening (12 hours apart) on a continuous daily dosing schedule. Each treatment cycle was defined as 28 days. Treatment continued until confirmation of RECIST version 1.1 defined disease progression assessed by the blinded independent central review (unless clinical benefit was still achievable), participant refusal, participant lost to follow-up, unacceptable toxicity, death, or the study was terminated by the sponsor, whichever occurred first.
| Group | Source count |
|---|---|
| Lorlatinib | 149 |
| Crizotinib | 147 |
Reported measurements
Source class 1
| Group | Value | Spread | Lower | Upper | Comment |
|---|---|---|---|---|---|
| Lorlatinib | NA | Not reported | NA | NA | The values were not estimable because there were insufficient events to estimate the median PFS time and 95% confidence interval. |
| Crizotinib | 9.3 | Not reported | 7.6 | 11.1 | Not reported |
Source statistical analyses
- ci Lower Limit
- 0.191
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 0.413
- estimate Comment
- Based on Cox Proportional Hazards model stratified by the presence of brain metastases and ethnic origin at randomization. Assuming proportional hazards, a hazard ratio less than 1 indicates a reduction in hazard rate in favor of Lorlatinib.
- group Description
- The study was designed to test the null hypothesis H0: λ ≥1 versus the alternative hypothesis HA: λ \<1, where λ is the hazard ratio (HR; Lorlatinib/Crizotinib). Evaluation of 177 PFS events was required to have at least 90% power to detect a HR of 0.611 using a one-sided stratified log-rank test at a significance level of 0.025 (one-sided), and a 2-look group-sequential design with a Lan-DeMets (O'Brien-Fleming) α-spending function to determine the efficacy boundaries.
- group Ids
- OG000
- OG001
- non Inferiority Type
- SUPERIORITY
- p Value
- <0.0001
- p Value Comment
- The study was to be considered positive if the 1-sided log-rank test for PFS, stratified for baseline stratification factors (ethnicity and brain metastases) was significant at the 0.0081 level at the cutoff date of this report.
- param Type
- Hazard Ratio (HR)
- param Value
- 0.28
- statistical Comment
- Stratified by the presence of brain metastases (Yes/No) and ethnic origin (Asian/Non-Asian) at randomization.
- statistical Method
- one-sided stratified log-rank
Complete source fields
- analyses
- ci Lower Limit
- 0.191
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 0.413
- estimate Comment
- Based on Cox Proportional Hazards model stratified by the presence of brain metastases and ethnic origin at randomization. Assuming proportional hazards, a hazard ratio less than 1 indicates a reduction in hazard rate in favor of Lorlatinib.
- group Description
- The study was designed to test the null hypothesis H0: λ ≥1 versus the alternative hypothesis HA: λ \<1, where λ is the hazard ratio (HR; Lorlatinib/Crizotinib). Evaluation of 177 PFS events was required to have at least 90% power to detect a HR of 0.611 using a one-sided stratified log-rank test at a significance level of 0.025 (one-sided), and a 2-look group-sequential design with a Lan-DeMets (O'Brien-Fleming) α-spending function to determine the efficacy boundaries.
- group Ids
- OG000
- OG001
- non Inferiority Type
- SUPERIORITY
- p Value
- <0.0001
- p Value Comment
- The study was to be considered positive if the 1-sided log-rank test for PFS, stratified for baseline stratification factors (ethnicity and brain metastases) was significant at the 0.0081 level at the cutoff date of this report.
- param Type
- Hazard Ratio (HR)
- param Value
- 0.28
- statistical Comment
- Stratified by the presence of brain metastases (Yes/No) and ethnic origin (Asian/Non-Asian) at randomization.
- statistical Method
- one-sided stratified log-rank
- classes
- categories
- measurements
- comment
- The values were not estimable because there were insufficient events to estimate the median PFS time and 95% confidence interval.
- group Id
- OG000
- lower Limit
- NA
- upper Limit
- NA
- value
- NA
- group Id
- OG001
- lower Limit
- 7.6
- upper Limit
- 11.1
- value
- 9.3
- denoms
- counts
- group Id
- OG000
- value
- 149
- group Id
- OG001
- value
- 147
- units
- Participants
- description
- PFS was defined as the time from randomization to the date of the first documentation of progressive disease as assessed by the independent radiologist or death due to any cause, whichever occurred first. PFS (in months) was calculated as (date of event or censoring-randomization+1)/30.4375. Progressive disease is defined per RECIST version 1.1, as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of 1 or more new lesions.
- dispersion Type
- 95% Confidence Interval
- groups
- description
- Lorlatinib monotherapy at the recommended Phase 2 dose of 100 mg, was administered orally once daily (QD) at approximately the same time of the day on a continuous daily dosing schedule. Each treatment cycle was defined as 28 days. Treatment continued until confirmation of RECIST version 1.1 defined disease progression assessed by the blinded independent central review (unless clinical benefit was still achievable), participant refusal, participant lost to follow-up, unacceptable toxicity, death, or the study was terminated by the sponsor, whichever occurred first.
- id
- OG000
- title
- Lorlatinib
- description
- Crizotinib monotherapy at the registered dose of 250 mg, was administered orally twice daily (BID) at approximately the same time in the morning and evening (12 hours apart) on a continuous daily dosing schedule. Each treatment cycle was defined as 28 days. Treatment continued until confirmation of RECIST version 1.1 defined disease progression assessed by the blinded independent central review (unless clinical benefit was still achievable), participant refusal, participant lost to follow-up, unacceptable toxicity, death, or the study was terminated by the sponsor, whichever occurred first.
- id
- OG001
- title
- Crizotinib
- param Type
- MEDIAN
- population Description
- The full analysis (FA) population included all participants who were randomized, and participants were classified according to the treatment assigned at randomization.
- reporting Status
- POSTED
- time Frame
- From time of Study Start up to 33 months
- title
- Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR) Assessment
- type
- PRIMARY
- unit Of Measure
- Months
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Preserved source evidence · Not medical advice