Trial Outcomes & Findings for A Molecular Profiling Study of Patients With EGFR Mutation-positive Locally Advanced or Metastatic NSCLC Treated With Osimertinib (NCT NCT03239340)
NCT ID: NCT03239340
Last Updated: 2024-10-21
Results Overview
The frequency of genetic and proteomic markers at disease progression regardless of their prevalence was evaluated.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
154 participants
Primary outcome timeframe
Genetic and proteomic markers were assessed at baseline and progression (up to 5 years after baseline)
Results posted on
2024-10-21
Participant Flow
Participants were enrolled in this study from 30 May 2018 (First subject in) and analyses presented in this results form are based on a final data cut-off of 18 July 2023 and final database lock of 15 December 2023.
Participants meeting eligibility criteria predefined in protocol were enrolled in the study. All the assessments were performed as per the schedule of the assessments.
Participant milestones
| Measure |
Osimertinib 80mg
Participants received Osimertinib 80mg orally once daily.
|
|---|---|
|
Overall Study
STARTED
|
154
|
|
Overall Study
COMPLETED
|
33
|
|
Overall Study
NOT COMPLETED
|
121
|
Reasons for withdrawal
| Measure |
Osimertinib 80mg
Participants received Osimertinib 80mg orally once daily.
|
|---|---|
|
Overall Study
Other
|
26
|
|
Overall Study
Patients who are ongoing in the study at DCO
|
10
|
|
Overall Study
Death
|
40
|
|
Overall Study
Lost to Follow-up
|
2
|
|
Overall Study
Physician Decision
|
16
|
|
Overall Study
Withdrawal by Subject
|
27
|
Baseline Characteristics
A Molecular Profiling Study of Patients With EGFR Mutation-positive Locally Advanced or Metastatic NSCLC Treated With Osimertinib
Baseline characteristics by cohort
| Measure |
Osimertinib 80mg
n=154 Participants
Participants received Osimertinib 80mg orally once daily.
|
|---|---|
|
Age, Continuous
|
62.7 Years
STANDARD_DEVIATION 10.36 • n=5 Participants
|
|
Sex: Female, Male
Female
|
92 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
62 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
30 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
5 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
118 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
6 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
148 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Genetic and proteomic markers were assessed at baseline and progression (up to 5 years after baseline)Population: The primary analysis set included all patients with evaluable paired biopsies, which were defined as follows: the first biopsy was taken prior to osimertinib treatment, and the second biopsy was taken at any time between Investigator-assessed RECIST 1.1-defined progression and before the start of any new anticancer treatment.
The frequency of genetic and proteomic markers at disease progression regardless of their prevalence was evaluated.
Outcome measures
| Measure |
Osimertinib 80 mg
n=51 Participants
Participants received Osimertinib 80mg orally once daily.
|
L858R
Patient with L858R received Osimertinib 80 mg orally one daily.
|
|---|---|---|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
BRAF; Short variant Type: V600E
|
3.9 Percentage of participants
Interval 0.48 to 13.46
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
CRKL Copy Number Alteration Type: amplification
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
CUL4A Copy Number Alteration Type: amplification
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
TET2 Short Variant Type: Q916*
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
AKT2; Copy Number Alteration: Type; amplification
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
ALK; Rearrangement
|
3.9 Percentage of participants
Interval 0.48 to 13.46
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
APC; Copy Number Alteration; Type: loss
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
ARAF; Copy Number Alteration; Type: amplification
|
3.9 Percentage of participants
Interval 0.48 to 13.46
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
ASXL1; Short Variant; Type: Q588*
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
ATRX; Short Variant; Type: P599fs*22
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
AXL; Copy Number Alteration; Type: amplification
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
BCL2L2; Copy Number Alteration; Type: amplification
|
3.9 Percentage of participants
Interval 0.48 to 13.46
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
BRAF; Rearrangement
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
BRAF; Short variant; Type: G469A
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
CBL; Short Variant; Type: R149Q
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
CCND1 Copy Number Alteration Type: amplification
|
3.9 Percentage of participants
Interval 0.48 to 13.46
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
CCNE1 Copy Number Alteration Type: amplification
|
5.9 Percentage of participants
Interval 1.23 to 16.24
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
CDK4 Copy Number Alteration Type: amplification
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
CDK6 Copy Number Alteration Type: amplification
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
CDKN1B Short Variant Type: S2*
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
CDKN2A Copy Number Alteration Type: loss
|
15.7 Percentage of participants
Interval 7.02 to 28.59
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
CDKN2A; Short Variant Type: P38L
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
CDKN2B Copy Number Alteration Type: loss
|
15.7 Percentage of participants
Interval 7.02 to 28.59
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
DIS3 Copy Number Alteration Type: amplification
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
EGFR Copy Number Alteration Type: amplification
|
11.8 Percentage of participants
Interval 4.44 to 23.87
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
EGFR Rearrangement
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
EGFR Short Variant Type: C797S
|
7 Percentage of participants
Interval 5.7 to 26.26
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
EGFR Short Variant Type: L858R
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
EMSY Copy Number Alteration Type: amplification
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
ERBB2 Copy Number Alteration Type: amplification
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
FANCG Rearrangement
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
FGF10 Copy Number Alteration Type: amplification
|
3.9 Percentage of participants
Interval 0.48 to 13.46
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
FGF14; Copy Number Alteration; Type: amplification
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
FGF19 Copy Number Alteration Type: amplification
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
FGFR1 Copy Number Alteration Type: amplification
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
FGFR3 Rearrangement
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
FGFR4 Copy Number Alteration Type: amplification
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
HGF Copy Number Alteration Type: amplification
|
3.9 Percentage of participants
Interval 0.48 to 13.46
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
HRAS Short Variant Type: Q61R
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
IDH1 Short Variant Type: R132L
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
IGF1R Copy Number Alteration Type: amplification
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
IRS2 Copy Number Alteration Type: amplification
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
KRAS Copy Number Alteration Type: amplification
|
3.9 Percentage of participants
Interval 0.48 to 13.46
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
LYN Copy Number Alteration Type: amplification
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
MAP2K1 Short Variant Type: E102_I103del
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
MCL1 Copy Number Alteration Type: amplification
|
5.9 Percentage of participants
Interval 1.23 to 16.24
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
MDM2 Copy Number Alteration Type: amplification
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
MET Copy Number Alteration Type: amplification
|
17.6 Percentage of participants
Interval 8.4 to 30.87
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
MTAP Copy Number Alteration Type: loss
|
13.7 Percentage of participants
Interval 5.7 to 26.26
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
MYC Copy Number Alteration Type: amplification
|
3.9 Percentage of participants
Interval 0.48 to 13.46
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
MYCN Copy Number Alteration Type: amplification
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
NF1 Short Variant Type: M1I
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
NFE2L2 Short Variant Type: D29N
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
NFKBIA Copy Number Alteration Type: amplification
|
9.8 Percentage of participants
Interval 3.26 to 21.41
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
NKX2-1 Copy Number Alteration Type: amplification
|
9.8 Percentage of participants
Interval 3.26 to 21.41
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
NOTCH3 Rearrangement
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
NTRK1 Copy Number Alteration Type: amplification
|
3.9 Percentage of participants
Interval 0.48 to 13.46
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
PARP1 Copy Number Alteration Type: amplification
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
PDGFRB Copy Number Alteration Type: amplification
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
PIK3CA Short Variant Type: E542K
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
PIM1 Copy Number Alteration Type: amplification
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
RAD21 Copy Number Alteration Type: amplification
|
3.9 Percentage of participants
Interval 0.48 to 13.46
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
RB1 Copy Number Alteration Type: loss
|
3.9 Percentage of participants
Interval 0.48 to 13.46
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
RB1 Short Variant Type: Q846*
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
RICTOR Copy Number Alteration Type: amplification
|
7.8 Percentage of participants
Interval 2.18 to 18.88
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
SMAD4 Rearrangement
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
SMAD4 Short Variant Type: W524L
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
SPEN Short Variant Type: D2047fs*17
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
STK11 Copy Number Alteration Type: loss
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
STK11 Short Variant Type: K269fs*18
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
TERC Copy Number Alteration Type: amplification
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
TERT Short Variant Type: promoter -146C>T
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
TET2 Short Variant Type: V1862fs*13
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
TP53 Short Variant Type: R213*
|
2.0 Percentage of participants
Interval 0.05 to 10.45
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
WHSC1L1 Copy Number Alteration Type: amplification
|
3.9 Percentage of participants
Interval 0.48 to 13.46
|
—
|
|
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
ZNF703 Copy Number Alteration Type: amplification
|
3.9 Percentage of participants
Interval 0.48 to 13.46
|
—
|
SECONDARY outcome
Timeframe: From date of first dose until date of progression or death (by any cause in the absence of recurrence), up to 5 yearsPopulation: The full analysis set included all patients who received at least one dose of Osimertinib.
PFS is defined as the time from first dose of osimertinib until the date of Investigator assessed Response Evaluation Criteria in Solid Tumours (RECIST) 1.1-defined progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from therapy or receives another anticancer therapy prior to progression.
Outcome measures
| Measure |
Osimertinib 80 mg
n=154 Participants
Participants received Osimertinib 80mg orally once daily.
|
L858R
Patient with L858R received Osimertinib 80 mg orally one daily.
|
|---|---|---|
|
Progression Free Survival (PFS)
|
16.4 Months
Interval 12.7 to 20.3
|
—
|
SECONDARY outcome
Timeframe: From date of first dose until progression, or last evaluable assessment in the absence of progression, up to 5 yearsPopulation: The full analysis set included all patients who received at least one dose of Osimertinib.
ORR is defined as the number (%) of patients with at least one visit response of complete response (CR) or partial response (PR) that is confirmed at least 4 weeks later.
Outcome measures
| Measure |
Osimertinib 80 mg
n=154 Participants
Participants received Osimertinib 80mg orally once daily.
|
L858R
Patient with L858R received Osimertinib 80 mg orally one daily.
|
|---|---|---|
|
Objective Response Rate (ORR)
|
73.4 Percentage of participants
Interval 65.66 to 80.17
|
—
|
SECONDARY outcome
Timeframe: From date of first documentation of complete/partial response until the date of progression, or last evaluable RECIST assessment for participants that did not progress within 2 missed visits of last assessment, up to 5 yearsPopulation: The full analysis set included all patients who received at least 1 dose of Osimertinib. The Duration of response is calculated for only participants with a confirmed response. Participants must have had measurable disease at baseline to be included in the study.
Duration of response is defined as the time from the date of first documented response, (that is subsequently confirmed) until date of documented progression or death in the absence of disease progression, the end of response should coincide with the date of progression or death from any cause used for the PFS endpoint. The time of the initial response will be defined as the latest of the dates contributing towards the first visit that was CR or PR that was subsequently confirmed.
Outcome measures
| Measure |
Osimertinib 80 mg
n=113 Participants
Participants received Osimertinib 80mg orally once daily.
|
L858R
Patient with L858R received Osimertinib 80 mg orally one daily.
|
|---|---|---|
|
Duration of Response (DoR)
|
18.8 Months
Interval 14.2 to 22.3
|
—
|
SECONDARY outcome
Timeframe: 8 weeksPopulation: The full analysis set included all patients who received at least 1 dose of osimertinib.
DCR is defined as percentage of patients with confirmed complete response, confirmed partial response or with stable disease.
Outcome measures
| Measure |
Osimertinib 80 mg
n=154 Participants
Participants received Osimertinib 80mg orally once daily.
|
L858R
Patient with L858R received Osimertinib 80 mg orally one daily.
|
|---|---|---|
|
Disease Control Rate (DCR)
|
94.8 Percentage of participants
Interval 90.02 to 97.73
|
—
|
SECONDARY outcome
Timeframe: From date of first dose to treatment discontinuation or death (by any cause in the absence of recurrence), up to 5 yearsPopulation: The full analysis set included all patients who received at least 1 dose of Osimertinib.
TTD is defined as the time from the date of first dose of osimertinib to the earliest of treatment discontinuation or death.
Outcome measures
| Measure |
Osimertinib 80 mg
n=154 Participants
Participants received Osimertinib 80mg orally once daily.
|
L858R
Patient with L858R received Osimertinib 80 mg orally one daily.
|
|---|---|---|
|
Time to Treatment Discontinuation or Death (TTD)
|
20.0 Months
Interval 16.3 to 23.8
|
—
|
SECONDARY outcome
Timeframe: From date of first dose to start of subsequent anticancer therapy or death (by any cause in the absence of recurrence), up to 5 yearsPopulation: The full analysis set included all patients who received at least 1 dose of Osimertinib.
TFST is defined as the time from the date of first dose of osimertinib to the earlier of the date of anticancer therapy start date following study treatment discontinuation, or death.
Outcome measures
| Measure |
Osimertinib 80 mg
n=154 Participants
Participants received Osimertinib 80mg orally once daily.
|
L858R
Patient with L858R received Osimertinib 80 mg orally one daily.
|
|---|---|---|
|
Time to First Subsequent Therapy or Death (TFST)
|
32.1 Months
Interval 24.0 to 47.7
|
—
|
SECONDARY outcome
Timeframe: From date of first dose until date of progression or death (by any cause in the absence of recurrence), up to 5 yearsPopulation: The full analysis set included all patients who received at least 1 dose of Osimertinib.
PFS is defined as the time from first dose of osimertinib until the date of Investigator assessed Response Evaluation Criteria in Solid Tumours (RECIST) 1.1-defined progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from therapy or receives another anticancer therapy prior to progression. PFS was analysed in patient subgroups defined by molecular profile, including but not limited to: EGFR tumor mutation at baseline-Exon19del or L858R
Outcome measures
| Measure |
Osimertinib 80 mg
n=85 Participants
Participants received Osimertinib 80mg orally once daily.
|
L858R
n=58 Participants
Patient with L858R received Osimertinib 80 mg orally one daily.
|
|---|---|---|
|
PFS in Patient Subgroups Defined by Molecular Profile: Epidermal Growth Factor Receptor (EGFR) Tumor Mutation at Baseline
|
22.0 Months
Interval 16.0 to 27.6
|
12.9 Months
Interval 10.8 to 18.2
|
SECONDARY outcome
Timeframe: From date of first dose until date of progression or death (by any cause in the absence of recurrence), up to 5 yearsPopulation: The full analysis set included all patients who received at least 1 dose of Osimertinib.
PFS is defined as the time from first dose of osimertinib until the date of Investigator assessed Response Evaluation Criteria in Solid Tumours (RECIST) 1.1-defined progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from therapy or receives another anticancer therapy prior to progression. PFS was analysed in patient subgroups defined by molecular profile, including but not limited to: Exon19del or L858R detectable in plasma derived circulating tumour deoxyribonucleic acid (ctDNA) at baseline.
Outcome measures
| Measure |
Osimertinib 80 mg
n=62 Participants
Participants received Osimertinib 80mg orally once daily.
|
L858R
n=46 Participants
Patient with L858R received Osimertinib 80 mg orally one daily.
|
|---|---|---|
|
PFS in Patient Subgroups Defined by Molecular Profile: Detectable in Plasma-Derived ctDNA at Baseline
|
19.6 Months
Interval 12.7 to 24.0
|
13.7 Months
Interval 9.0 to 18.2
|
SECONDARY outcome
Timeframe: From date of first dose until progression, or last evaluable assessment in the absence of progression, up to 5 yearsPopulation: The full analysis set included all patients who received at least 1 dose of Osimertinib.
ORR is defined as the number (%) of patients with at least one visit response of complete response or partial response that is confirmed at least 4 weeks later. ORR was analysed in patient subgroups defined by molecular profile: EGFR tumor mutation at baseline-Exon19del or L858R
Outcome measures
| Measure |
Osimertinib 80 mg
n=85 Participants
Participants received Osimertinib 80mg orally once daily.
|
L858R
n=58 Participants
Patient with L858R received Osimertinib 80 mg orally one daily.
|
|---|---|---|
|
ORR in Patient Subgroups Defined by Molecular Profile: EGFR Tumor Mutation at Baseline
|
82.4 Percentage of participants
Interval 72.57 to 89.77
|
69.0 Percentage of participants
Interval 55.46 to 80.46
|
SECONDARY outcome
Timeframe: From date of first dose until progression, or last evaluable assessment in the absence of progression, up to 5 yearsPopulation: The full analysis set included all patients who received at least 1 dose of Osimertinib.
ORR is defined as the number (%) of patients with at least one visit response of complete response or partial response that is confirmed at least 4 weeks later. ORR was analysed in patient subgroups defined by molecular profile: Exon19del or L858R detectable in plasma derived ctDNA at baseline.
Outcome measures
| Measure |
Osimertinib 80 mg
n=62 Participants
Participants received Osimertinib 80mg orally once daily.
|
L858R
n=46 Participants
Patient with L858R received Osimertinib 80 mg orally one daily.
|
|---|---|---|
|
ORR in Patient Subgroups Defined by Molecular Profile: Detectable in Plasma Derived ctDNA at Baseline
|
85.5 Percentage of participants
Interval 74.22 to 93.14
|
71.7 Percentage of participants
Interval 56.54 to 84.01
|
SECONDARY outcome
Timeframe: From date of first dose to treatment discontinuation or death (by any cause in the absence of recurrence), up to 5 yearsPopulation: The full analysis set included all patients who received at least 1 dose of Osimertinib.
TTD is defined as the time from the date of first dose of osimertinib to the earliest of treatment discontinuation or death. TTD was analysed in patient subgroups defined by molecular profile: EGFR tumor mutation at baseline-Exon19del or L858R
Outcome measures
| Measure |
Osimertinib 80 mg
n=85 Participants
Participants received Osimertinib 80mg orally once daily.
|
L858R
n=58 Participants
Patient with L858R received Osimertinib 80 mg orally one daily.
|
|---|---|---|
|
TTD in Patient Subgroups Defined by Molecular Profile: EGFR Tumor Mutation at Baseline
|
25.5 Months
Interval 19.6 to 32.1
|
16.5 Months
Interval 12.1 to 21.7
|
SECONDARY outcome
Timeframe: From date of first dose to treatment discontinuation or death (by any cause in the absence of recurrence), up to 5 yearsPopulation: The full analysis set included all patients who received at least 1 dose of Osimertinib.
TTD is defined as the time from the date of first dose of osimertinib to the earliest of treatment discontinuation or death. TTD was analysed in patient subgroups defined by molecular profile: Exon19del or L858R detectable in plasma derived ctDNA at baseline.
Outcome measures
| Measure |
Osimertinib 80 mg
n=62 Participants
Participants received Osimertinib 80mg orally once daily.
|
L858R
n=46 Participants
Patient with L858R received Osimertinib 80 mg orally one daily.
|
|---|---|---|
|
TTD in Patient Subgroups Defined by Molecular Profile: Detectable in Plasma Derived ctDNA at Baseline
|
24.5 Months
Interval 17.8 to 29.6
|
16.5 Months
Interval 12.1 to 21.4
|
SECONDARY outcome
Timeframe: From date of first dose until last recorded post baseline RECIST target lesion assessment scan, up to 5 yearsPopulation: The full analysis set included all patients who received at least 1 dose of Osimertinib.
Tumour shrinkage is defined as the best change from baseline in the sum of diameters of target lesions, in patient subgroups defined by molecular profile: EGFR tumor mutation at baseline-Exon19del or L858R. A negative change denotes a reduction in target lesion size.
Outcome measures
| Measure |
Osimertinib 80 mg
n=83 Participants
Participants received Osimertinib 80mg orally once daily.
|
L858R
n=55 Participants
Patient with L858R received Osimertinib 80 mg orally one daily.
|
|---|---|---|
|
Tumour Shrinkage/Depth of Response in Patient Subgroups Defined by Molecular Profile: EGFR Tumor Mutation at Baseline
|
-59.68 Percentage change
Interval -100.0 to 6.5
|
-54.29 Percentage change
Interval -100.0 to 7.6
|
SECONDARY outcome
Timeframe: From date of first dose until last recorded post baseline RECIST target lesion assessment scan, up to 5 yearsPopulation: The full analysis set included all patients who received at least 1 dose of Osimertinib.
Tumour shrinkage is defined as the best change from baseline in the sum of diameters of target lesions, in patient subgroups defined by molecular profile: Exon19del or L858R detectable in plasma derived ctDNA at baseline. A negative change denotes a reduction in target lesion size.
Outcome measures
| Measure |
Osimertinib 80 mg
n=60 Participants
Participants received Osimertinib 80mg orally once daily.
|
L858R
n=44 Participants
Patient with L858R received Osimertinib 80 mg orally one daily.
|
|---|---|---|
|
Tumour Shrinkage/Depth of Response in Patient Subgroups Defined by Molecular Profile: Detectable in Plasma Derived ctDNA at Baseline
|
-60.80 Percentage change
Interval -100.0 to 6.5
|
-58.33 Percentage change
Interval -100.0 to 7.6
|
Adverse Events
Osimertinib 80 mg
Serious events: 53 serious events
Other events: 148 other events
Deaths: 40 deaths
Serious adverse events
| Measure |
Osimertinib 80 mg
n=154 participants at risk
Participants received Osimertinib 80mg orally once daily.
|
|---|---|
|
Infections and infestations
COVID-19
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Infections and infestations
Gastroenteritis
|
1.3%
2/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Infections and infestations
Lower respiratory tract infection
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Infections and infestations
Pneumonia
|
7.8%
12/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Infections and infestations
Pneumonia aspiration
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Infections and infestations
Respiratory tract infection
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Infections and infestations
Sepsis
|
2.6%
4/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Infections and infestations
Tuberculosis
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Infections and infestations
Urinary tract infection
|
1.9%
3/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Infections and infestations
Urosepsis
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix carcinoma
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Blood and lymphatic system disorders
Anaemia
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Blood and lymphatic system disorders
Blood loss anaemia
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Blood and lymphatic system disorders
Immune thrombocytopenia
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Endocrine disorders
Adrenal insufficiency
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Metabolism and nutrition disorders
Hyperglycaemic hyperosmolar nonketotic syndrome
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
1.3%
2/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Psychiatric disorders
Confusional state
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Psychiatric disorders
Mania
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Nervous system disorders
Spinal cord compression
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Nervous system disorders
Status epilepticus
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Cardiac disorders
Acute coronary syndrome
|
1.3%
2/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Cardiac disorders
Atrial fibrillation
|
1.9%
3/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Cardiac disorders
Cardiac failure
|
1.3%
2/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Cardiac disorders
Cardiac failure acute
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Vascular disorders
Deep vein thrombosis
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Vascular disorders
Embolism
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.3%
2/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
1.3%
2/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
1.3%
2/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Gastrointestinal disorders
Duodenitis
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Gastrointestinal disorders
Gastritis
|
1.9%
3/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Gastrointestinal disorders
Vomiting
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Hepatobiliary disorders
Cholecystitis
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Skin and subcutaneous tissue disorders
Subcutaneous emphysema
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
General disorders
Asthenia
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
General disorders
General physical health deterioration
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Investigations
Platelet count decreased
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Investigations
Neutrophil count decreased
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Renal and urinary disorders
Acute kidney injury
|
1.3%
2/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Renal and urinary disorders
Haematuria
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Renal and urinary disorders
Renal impairment
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Investigations
Electrocardiogram QT prolonged
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Injury, poisoning and procedural complications
Fibula fracture
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Injury, poisoning and procedural complications
Foreign body aspiration
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Injury, poisoning and procedural complications
Pelvic fracture
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Injury, poisoning and procedural complications
Wound dehiscence
|
0.65%
1/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
2.6%
4/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
Other adverse events
| Measure |
Osimertinib 80 mg
n=154 participants at risk
Participants received Osimertinib 80mg orally once daily.
|
|---|---|
|
Infections and infestations
COVID-19
|
9.1%
14/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Infections and infestations
Paronychia
|
23.4%
36/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Infections and infestations
Upper respiratory tract infection
|
15.6%
24/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Infections and infestations
Urinary tract infection
|
10.4%
16/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Blood and lymphatic system disorders
Anaemia
|
16.9%
26/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
5.8%
9/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Metabolism and nutrition disorders
Decreased appetite
|
17.5%
27/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Psychiatric disorders
Insomnia
|
6.5%
10/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Nervous system disorders
Dizziness
|
7.1%
11/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
20.8%
32/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Nervous system disorders
Headache
|
7.1%
11/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
5.2%
8/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Gastrointestinal disorders
Constipation
|
8.4%
13/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Gastrointestinal disorders
Diarrhoea
|
40.9%
63/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Gastrointestinal disorders
Gastritis
|
5.2%
8/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Gastrointestinal disorders
Mouth ulceration
|
9.7%
15/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Gastrointestinal disorders
Nausea
|
11.0%
17/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Gastrointestinal disorders
Stomatitis
|
14.3%
22/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Gastrointestinal disorders
Vomiting
|
9.1%
14/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
13.6%
21/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
19.5%
30/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
14.9%
23/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Skin and subcutaneous tissue disorders
Rash
|
16.9%
26/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
10.4%
16/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
11.7%
18/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
6.5%
10/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
General disorders
Asthenia
|
8.4%
13/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
General disorders
Fatigue
|
7.1%
11/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Investigations
Alanine aminotransferase increased
|
10.4%
16/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Investigations
Aspartate aminotransferase increased
|
9.1%
14/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Investigations
Gamma-glutamyltransferase increased
|
5.8%
9/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Investigations
Platelet count decreased
|
7.1%
11/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Investigations
Weight decreased
|
7.1%
11/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
5.8%
9/154 • From Day 1 to Follow-up (28 days post last dose) up to 5 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee No unpublished information contained herein may be disclosed without prior written approval from AstraZeneca AB. Access to this document must be restricted to relevant parties.
- Publication restrictions are in place
Restriction type: OTHER