Trial Outcomes & Findings for A Global Study to Assess the Effects of Osimertinib Following Chemoradiation in Patients With Stage III Unresectable Non-small Cell Lung Cancer (LAURA) (NCT NCT03521154)

Last Updated: 2025-10-16

Results Overview

Time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomised therapy or receives another anti-cancer therapy prior to progression, based on BICR assessment according to RECIST v1.1

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

216 participants

Primary outcome timeframe

Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months

Results posted on

2025-10-16

Participant Flow

Patients assigned to osimertinib may continue to receive osimertinib if, in the opinion of their treating physician, they are continuing to derive clinical benefit. Patients receiving placebo may receive open-label osimertinib, in accordance with local clinical practice and the judgement of their treating physician. For all patients, post-progression treatment with AZ-supply osimertinib may continue as long as the treating physician considers the patient to be deriving clinical benefit

Participant milestones

Participant milestones
Measure	Osimertinib 80mg once daily tablet	Placebo Matching Placebo
Overall Study STARTED	143	73
Overall Study COMPLETED	32	21
Overall Study NOT COMPLETED	111	52

Reasons for withdrawal

Reasons for withdrawal
Measure	Osimertinib 80mg once daily tablet	Placebo Matching Placebo
Overall Study Ongoing study at data cut-off	111	52

Baseline Characteristics

A Global Study to Assess the Effects of Osimertinib Following Chemoradiation in Patients With Stage III Unresectable Non-small Cell Lung Cancer (LAURA)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Osimertinib n=143 Participants 80mg once daily tablet	Placebo n=73 Participants Matching Placebo	Total n=216 Participants Total of all reporting groups
Age, Continuous	62 Years n=5 Participants	64 Years n=7 Participants	62.5 Years n=5 Participants
Sex: Female, Male Female	90 Participants n=5 Participants	42 Participants n=7 Participants	132 Participants n=5 Participants
Sex: Female, Male Male	53 Participants n=5 Participants	31 Participants n=7 Participants	84 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	11 Participants n=5 Participants	2 Participants n=7 Participants	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	132 Participants n=5 Participants	71 Participants n=7 Participants	203 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Asian	116 Participants n=5 Participants	62 Participants n=7 Participants	178 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	20 Participants n=5 Participants	10 Participants n=7 Participants	30 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Osimertinib n=143 Participants 80mg once daily tablet	Placebo n=73 Participants Matching Placebo
Progression-free Survival (PFS) by Blinded Independent Central Review (BICR)	39.13 Months Interval 31.51 to NA - Not calculated as insufficient number of events to enable the upper limit of 95% confidence interval to be calculated	5.55 Months Interval 3.71 to 7.43

SECONDARY outcome

Timeframe: Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months

Population: Full analysis set

Number of PFS events (PFS is time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomised therapy or receives another anti-cancer therapy prior to progression, based on BICR assessment according to RECIST v1.1)

Outcome measures

Outcome measures
Measure	Osimertinib n=143 Participants 80mg once daily tablet	Placebo n=73 Participants Matching Placebo
Number of Participants With Progression-free Survival (PFS) Events in Patients With EGFR Ex19del or L858R Mutation Ex19Del positive	26 Participants	39 Participants
Number of Participants With Progression-free Survival (PFS) Events in Patients With EGFR Ex19del or L858R Mutation L858R positive	31 Participants	24 Participants
Number of Participants With Progression-free Survival (PFS) Events in Patients With EGFR Ex19del or L858R Mutation Missing	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Osimertinib n=143 Participants 80mg once daily tablet	Placebo n=73 Participants Matching Placebo
Number of Participants With Progression-free Survival (PFS) Events in Patients With EGFR Mutations Ex19del or L858R Detectable in Plasma-derived ctDNA EGFR mutation-positive	4 Participants	4 Participants
Number of Participants With Progression-free Survival (PFS) Events in Patients With EGFR Mutations Ex19del or L858R Detectable in Plasma-derived ctDNA EGFR mutation-negative	42 Participants	51 Participants
Number of Participants With Progression-free Survival (PFS) Events in Patients With EGFR Mutations Ex19del or L858R Detectable in Plasma-derived ctDNA EGFR mutation-unknown	11 Participants	8 Participants

SECONDARY outcome

Timeframe: Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months

Population: Full analysis set

Time from randomisation until the date of CNS disease progression or death (by any cause in the absence of CNS progression) regardless of whether the patient withdraws from randomised therapy or receives another anti-cancer therapy prior to progression, based on CNS BICR assessment according to RECIST v1.1

Outcome measures

Outcome measures
Measure	Osimertinib n=143 Participants 80mg once daily tablet	Placebo n=73 Participants Matching Placebo
Central Nervous System (CNS) Progression-free Survival (PFS) by Blinded Independent Central Review (BICR)	NA Months NA - Not calculated as insufficient number of events to enable the median and 95% confidence interval to be calculated	14.88 Months Interval 7.36 to NA - Not calculated as insufficient number of events to enable the upper limit of the 95% confidence interval to be calculated

SECONDARY outcome

Timeframe: Date of randomisation to date of death by any cause. Assessed up to a maximum of approximately 63 months

Population: Full analysis set

Number of patients with Overall Survival (OS), the time from the date of randomisation until date of death by any cause

Outcome measures

Outcome measures
Measure	Osimertinib n=143 Participants 80mg once daily tablet	Placebo n=73 Participants Matching Placebo
Overall Survival (Count) Died	28 Participants	15 Participants
Overall Survival (Count) Censored (includes participants still in survival follow up and terminated prior to death)	115 Participants	58 Participants

SECONDARY outcome

Timeframe: Date of randomisation to date of death by any cause. Assessed up to a maximum of approximately 63 months

Population: Full analysis set

Time from the date of randomisation until death by any cause

Outcome measures

Outcome measures
Measure	Osimertinib n=143 Participants 80mg once daily tablet	Placebo n=73 Participants Matching Placebo
Overall Survival (Duration)	53.95 Months Interval 46.49 to NA - Not calculated as insufficient number of events to enable upper limit of 95% confidence interval to be calculated	NA Months Interval 42.05 to NA - Not calculated as insufficient number of events to enable median and upper limit of 95% confidence interval to be calculated

SECONDARY outcome

Timeframe: Every 8 weeks for first 48 weeks, then every 12 weeks until radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months

Population: Full analysis set

Percentage of evaluable patients with at least one BICR assessed visit response of complete response (CR) or partial response (PR). CR defined as disappearance of all target lesions (TL) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10mm. PR defined as \>= 30% decrease in the sum of diameters of target lesions (compared to baseline sum of diameters). Responses include both confirmed and unconfirmed BICR responses

Outcome measures

Outcome measures
Measure	Osimertinib n=143 Participants 80mg once daily tablet	Placebo n=73 Participants Matching Placebo
Objective Response Rate by Blinded Independent Central Review (BICR)	57.3 % of participants Interval 48.8 to 65.6	32.9 % of participants Interval 22.3 to 44.9

SECONDARY outcome

Timeframe: Every 8 weeks for first 48 weeks, then every 12 weeks until radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months

Population: Full analysis set

Date of PFS event - date of first unconfirmed response + 1 day (and expressed in months) for unconfirmed responses only

Outcome measures

Outcome measures
Measure	Osimertinib n=82 Participants 80mg once daily tablet	Placebo n=24 Participants Matching Placebo
Duration of Response, Unconfirmed by Blinded Independent Central Review (BICR)	36.9 Months Interval 17.9 to NA - Not calculated as insufficient number of events to enable 75% percentile to be calculated	6.5 Months Interval 3.2 to 9.0

SECONDARY outcome

Timeframe: Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months

Population: Full analysis set

Percentage of patients who have a best overall response of complete response (CR), partial response (PR) or stable disease (SD) as assessed by BICR

Outcome measures

Outcome measures
Measure	Osimertinib n=143 Participants 80mg once daily tablet	Placebo n=73 Participants Matching Placebo
Disease Control Rate by Blinded Independent Central Review (BICR)	88.8 % of participants Interval 82.5 to 93.5	79.5 % of participants Interval 68.4 to 88.0

SECONDARY outcome

Timeframe: Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months

Population: Full analysis set

Depth of response (or tumour shrinkage or change in tumour size) was assessed using BICR responses in target lesions. The best change in tumour size is the largest decrease from baseline or the smallest increase from baseline in the absence of a reduction

Outcome measures

Outcome measures
Measure	Osimertinib n=133 Participants 80mg once daily tablet	Placebo n=70 Participants Matching Placebo
Tumour Shrinkage by Blinded Independent Central Review (BICR)	-43.3 % change from baseline Interval -100.0 to 144.0	-21.9 % change from baseline Interval -100.0 to 23.0

SECONDARY outcome

Timeframe: Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months

Population: Full analysis set

Proportion with depth of response (or tumour shrinkage or change in tumour size)

Outcome measures

Outcome measures
Measure	Osimertinib n=143 Participants 80mg once daily tablet	Placebo n=73 Participants Matching Placebo
Proportion With Tumour Shrinkage by Blinded Independent Central Review (BICR) Proportion with reduction > 50%	0.43 Proportion of participants	0.11 Proportion of participants
Proportion With Tumour Shrinkage by Blinded Independent Central Review (BICR) Proportion with reduction	0.92 Proportion of participants	0.83 Proportion of participants
Proportion With Tumour Shrinkage by Blinded Independent Central Review (BICR) Proportion with reduction > 30%	0.65 Proportion of participants	0.40 Proportion of participants
Proportion With Tumour Shrinkage by Blinded Independent Central Review (BICR) Proportion with reduction > 75%	0.18 Proportion of participants	0.09 Proportion of participants

SECONDARY outcome

Timeframe: Time from randomisation to the date of distant metastases or death. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months

Population: Full analysis set

Time from the date of randomisation until the first date of distant metastases or date of death in the absence of distant metastasis. Distant metastasis is defined as any new lesion that is detected on a scan that is anywhere other than lung or regional lymph node according to RECIST v1.1 or proven by biopsy

Outcome measures

Outcome measures
Measure	Osimertinib n=143 Participants 80mg once daily tablet	Placebo n=73 Participants Matching Placebo
Time to Death or Distant Metastases by Blinded Independent Central Review (BICR)	NA Months Interval 39.29 to NA - Not calculated as median not reached and insufficient number of events to enable upper limit of 95% confidence interval to be calculated	13.04 Months Interval 9.03 to NA - Not calculated as insufficient number of events to enable upper limit of 95% confidence interval to be calculated

SECONDARY outcome

Timeframe: Time from randomisation to the earlier of the date of study treatment discontinuation or death. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months

Population: Full analysis set

Time from randomisation to the earlier of the date of study treatment discontinuation (regardless of the reason for study treatment discontinuation) or death (i.e. date of study treatment discontinuation/death or censoring - date of randomisation + 1 day, expressed in months)

Outcome measures

Outcome measures
Measure	Osimertinib n=143 Participants 80mg once daily tablet	Placebo n=73 Participants Matching Placebo
Time to Study Treatment Discontinuation	40.28 Months Interval 32.72 to NA - Not calculated as insufficient number of events to enable the upper limit of the 95% confidence interval to be calculated	8.31 Months Interval 6.14 to 11.1

SECONDARY outcome

Timeframe: Time from randomisation to the start of first subsequent anti-cancer therapy or death. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months

Population: Full analysis set

Time from the date of randomisation to the earlier of the date of anti-cancer therapy start date following study drug discontinuation or death

Outcome measures

Outcome measures
Measure	Osimertinib n=143 Participants 80mg once daily tablet	Placebo n=73 Participants Matching Placebo
Time to First Subsequent Treatment	43.83 Months Interval 38.87 to NA - Not calculated as insufficient number of events to enable the upper limit of 95% confidence interval to be calculated	9.46 Months Interval 6.6 to 11.53

SECONDARY outcome

Timeframe: Time from randomisation to the start of second subsequent anti-cancer therapy or death. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months

Population: Full analysis set

Time from the date of randomisation to the earlier of the second subsequent anti-cancer therapy start date following study drug discontinuation or death

Outcome measures

Outcome measures
Measure	Osimertinib n=143 Participants 80mg once daily tablet	Placebo n=73 Participants Matching Placebo
Time to Second Subsequent Treatment	NA Months Interval 44.42 to NA - Not calculated as insufficient number of events to enable the median and upper limit of 95% confidence interval to be calculated	47.38 Months Interval 34.14 to NA - Not calculated as insufficient number of events to enable the upper limit of 95% confidence interval to be calculated

SECONDARY outcome

Timeframe: Every 8 weeks for first 48 weeks, then every 12 weeks. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months

Population: Full analysis set

Time from randomisation to the earliest progression event following first objective disease progression, subsequent to the first subsequent therapy, or death.

Outcome measures

Outcome measures
Measure	Osimertinib n=143 Participants 80mg once daily tablet	Placebo n=73 Participants Matching Placebo
Second Progression-free Survival (PFS2)	48.20 Months Interval 44.42 to NA - Not calculated as insufficient number of events to enable the upper limit of 95% confidence interval to be calculated	47.38 Months Interval 28.22 to NA - Not calculated as insufficient number of events to enable the upper limit of 95% confidence interval to be calculated

Adverse Events

Osimertinib

Serious events: 55 serious events

Other events: 129 other events

Deaths: 28 deaths

Placebo

Serious events: 11 serious events

Other events: 54 other events

Deaths: 15 deaths

Serious adverse events

Other adverse events

Additional Information

Global Clinical Lead

AstraZeneca Clinical Study Information Center

Phone: 1-877-240-9479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Osimertinib n=143 participants at risk 80mg once daily tablet	Placebo n=73 participants at risk Matching Placebo
Gastrointestinal disorders Large intestine polyp	0.70% 1/143 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Gastrointestinal disorders Nausea	0.00% 0/143 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	1.4% 1/73 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Gastrointestinal disorders Oesophageal stenosis	0.70% 1/143 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
General disorders Malaise	0.00% 0/143 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	1.4% 1/73 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Hepatobiliary disorders Hepatic failure	0.70% 1/143 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Infections and infestations Bacterial pyelonephritis	0.70% 1/143 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Infections and infestations Biliary tract infection	0.70% 1/143 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Infections and infestations Bronchitis	0.70% 1/143 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Blood and lymphatic system disorders Anaemia	0.70% 1/143 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Infections and infestations Covid-19	0.70% 1/143 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Infections and infestations Chronic hepatitis b	0.70% 1/143 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Infections and infestations Dengue fever	0.70% 1/143 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Infections and infestations Gastroenteritis	1.4% 2/143 • Number of events 2 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Infections and infestations Pneumocystis jirovecii pneumonia	0.70% 1/143 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Infections and infestations Pneumonia	4.9% 7/143 • Number of events 7 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	4.1% 3/73 • Number of events 3 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Infections and infestations Pneumonia aspiration	0.00% 0/143 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	1.4% 1/73 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Blood and lymphatic system disorders Thrombocytopenia	0.70% 1/143 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Infections and infestations Pneumonia viral	0.70% 1/143 • Number of events 2 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Injury, poisoning and procedural complications Femur fracture	0.70% 1/143 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Injury, poisoning and procedural complications Meniscus injury	0.70% 1/143 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Injury, poisoning and procedural complications Radiation pneumonitis	10.5% 15/143 • Number of events 15 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	2.7% 2/73 • Number of events 2 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Injury, poisoning and procedural complications Road traffic accident	0.70% 1/143 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Injury, poisoning and procedural complications Upper limb fracture	0.70% 1/143 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Investigations Alanine aminotransferase increased	0.70% 1/143 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Cardiac disorders Acute myocardial infarction	0.70% 1/143 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign ovarian tumour	0.70% 1/143 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bowen's disease	0.70% 1/143 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.00% 0/143 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	1.4% 1/73 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.70% 1/143 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Cardiac disorders Aortic valve disease	0.70% 1/143 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small intestine carcinoma	0.70% 1/143 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Nervous system disorders Cerebrovascular accident	0.00% 0/143 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	1.4% 1/73 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Renal and urinary disorders Prerenal failure	0.70% 1/143 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Renal and urinary disorders Ureterolithiasis	0.70% 1/143 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Reproductive system and breast disorders Uterine prolapse	0.70% 1/143 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.70% 1/143 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.70% 1/143 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Cardiac disorders Myocardial infarction	0.00% 0/143 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	1.4% 1/73 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.70% 1/143 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	1.4% 1/73 • Number of events 2 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.4% 2/143 • Number of events 2 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment

Other adverse events
Measure	Osimertinib n=143 participants at risk 80mg once daily tablet	Placebo n=73 participants at risk Matching Placebo
Gastrointestinal disorders Stomatitis	11.9% 17/143 • Number of events 20 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	2.7% 2/73 • Number of events 2 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Blood and lymphatic system disorders Anaemia	9.1% 13/143 • Number of events 16 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	4.1% 3/73 • Number of events 3 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Infections and infestations Covid-19	19.6% 28/143 • Number of events 28 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	8.2% 6/73 • Number of events 6 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Infections and infestations Herpes zoster	9.1% 13/143 • Number of events 13 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	2.7% 2/73 • Number of events 2 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Infections and infestations Nasopharyngitis	5.6% 8/143 • Number of events 9 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Infections and infestations Paronychia	16.8% 24/143 • Number of events 29 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	1.4% 1/73 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Infections and infestations Pneumonia	7.0% 10/143 • Number of events 10 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	4.1% 3/73 • Number of events 5 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Infections and infestations Upper respiratory tract infection	7.0% 10/143 • Number of events 18 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	1.4% 1/73 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Infections and infestations Urinary tract infection	7.7% 11/143 • Number of events 13 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	2.7% 2/73 • Number of events 2 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Injury, poisoning and procedural complications Radiation pneumonitis	38.5% 55/143 • Number of events 55 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	35.6% 26/73 • Number of events 27 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Investigations Alanine aminotransferase increased	7.0% 10/143 • Number of events 12 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	2.7% 2/73 • Number of events 2 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Investigations Aspartate aminotransferase increased	5.6% 8/143 • Number of events 11 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	1.4% 1/73 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Investigations Platelet count decreased	5.6% 8/143 • Number of events 14 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	0.00% 0/73 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Investigations White blood cell count decreased	11.9% 17/143 • Number of events 35 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	2.7% 2/73 • Number of events 2 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Metabolism and nutrition disorders Decreased appetite	14.7% 21/143 • Number of events 23 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	5.5% 4/73 • Number of events 4 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Musculoskeletal and connective tissue disorders Arthralgia	7.0% 10/143 • Number of events 12 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	8.2% 6/73 • Number of events 7 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	3.5% 5/143 • Number of events 5 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	12.3% 9/73 • Number of events 9 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Musculoskeletal and connective tissue disorders Myalgia	3.5% 5/143 • Number of events 5 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	8.2% 6/73 • Number of events 7 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Nervous system disorders Headache	1.4% 2/143 • Number of events 2 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	5.5% 4/73 • Number of events 4 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Respiratory, thoracic and mediastinal disorders Cough	16.1% 23/143 • Number of events 29 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	9.6% 7/73 • Number of events 7 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.6% 8/143 • Number of events 9 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	6.8% 5/73 • Number of events 5 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Respiratory, thoracic and mediastinal disorders Productive cough	4.9% 7/143 • Number of events 7 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	5.5% 4/73 • Number of events 4 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Skin and subcutaneous tissue disorders Dermatitis acneiform	6.3% 9/143 • Number of events 9 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	2.7% 2/73 • Number of events 2 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Skin and subcutaneous tissue disorders Dry skin	12.6% 18/143 • Number of events 22 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	5.5% 4/73 • Number of events 4 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Skin and subcutaneous tissue disorders Pruritus	12.6% 18/143 • Number of events 20 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	6.8% 5/73 • Number of events 5 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Skin and subcutaneous tissue disorders Rash	23.8% 34/143 • Number of events 40 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	13.7% 10/73 • Number of events 11 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Cardiac disorders Sinus tachycardia	5.6% 8/143 • Number of events 12 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	1.4% 1/73 • Number of events 1 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment
Gastrointestinal disorders Diarrhoea	35.7% 51/143 • Number of events 67 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment	13.7% 10/73 • Number of events 11 • From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug. The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment