Trial Outcomes & Findings for AZD9291 (Osimertinib) Versus Platinum-Based Doublet-Chemotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NCT NCT02151981)

NCT ID: NCT02151981

Last Updated: 2025-01-07

Results Overview

Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Progressive Disease (PD): \>= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of \>=5mm (compared to the previous minimum sum) or progression of NTLs or a new lesion. PFS is the time from date of randomisation until the date of PD (by investigator assessment) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression. Patients who had not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST 1.1 assessment.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

421 participants

Primary outcome timeframe

RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).

Results posted on

2025-01-07

Participant Flow

First patient dosed: 20 August 2014. Data cut off: 15 March 2019. Open for enrolment at 145 study centres, 126 centres in 17 countries randomised patients to treatment. Following the final OS analysis, patients were permitted to continue to receive treatment if, in the investigator's opinion, they were continuing to receive benefit from treatment. The last patient completed the study on the 15 December 2023

Participant milestones

Participant milestones
Measure	Osimertinib 80 mg Daily single dose of Osimertinib 80mg	Chemotherapy Platinum-based doublet chemotherapy
Overall Study STARTED	279	140
Overall Study Received Randomised Treatment Only	279	136
Overall Study Did Not Receive Treatment	0	4
Overall Study Crossed Over Osimertinib	0	99
Overall Study COMPLETED	60	27
Overall Study NOT COMPLETED	219	113

Reasons for withdrawal

Reasons for withdrawal
Measure	Osimertinib 80 mg Daily single dose of Osimertinib 80mg	Chemotherapy Platinum-based doublet chemotherapy
Overall Study Death	184	88
Overall Study Lost to Follow-up	7	1
Overall Study Withdrawal by Subject	27	21
Overall Study Eligibility criteria not fulfilled	0	1
Overall Study Other reasons	1	2

Baseline Characteristics

AZD9291 (Osimertinib) Versus Platinum-Based Doublet-Chemotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Osimertinib 80 mg n=279 Participants Daily single dose of Osimertinib 80mg	Chemotherapy n=140 Participants Platinum-based doublet chemotherapy	Total n=419 Participants Total of all reporting groups
Age, Continuous	61.5 Years STANDARD_DEVIATION 11.64 • n=99 Participants	62.0 Years STANDARD_DEVIATION 11.91 • n=107 Participants	61.7 Years STANDARD_DEVIATION 11.72 • n=206 Participants
Sex: Female, Male Female	172 Participants n=99 Participants	97 Participants n=107 Participants	269 Participants n=206 Participants
Sex: Female, Male Male	107 Participants n=99 Participants	43 Participants n=107 Participants	150 Participants n=206 Participants
Race/Ethnicity, Customized Asian	182 Participants n=99 Participants	92 Participants n=107 Participants	274 Participants n=206 Participants
Race/Ethnicity, Customized Black Or African American	4 Participants n=99 Participants	1 Participants n=107 Participants	5 Participants n=206 Participants
Race/Ethnicity, Customized Other	4 Participants n=99 Participants	1 Participants n=107 Participants	5 Participants n=206 Participants
Race/Ethnicity, Customized White	89 Participants n=99 Participants	45 Participants n=107 Participants	134 Participants n=206 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants

PRIMARY outcome

Timeframe: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).

Population: Full Analysis Set (All randomised patients)

Outcome measures

Outcome measures
Measure	Osimertinib 80mg n=140 Events Daily single dose of Osimertinib 80mg	Chemotherapy n=110 Events Platinum-based doublet chemotherapy
Progression Free Survival (PFS) by Investigator Assessment	10.1 Months Interval 8.3 to 12.3	4.4 Months Interval 4.2 to 5.6

SECONDARY outcome

Timeframe: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).

Population: Full Analysis Set (All randomised patients)

Outcome measures

Outcome measures
Measure	Osimertinib 80mg n=279 Participants Daily single dose of Osimertinib 80mg	Chemotherapy n=140 Participants Platinum-based doublet chemotherapy
Objective Response Rate (ORR) by Investigator Assessment	70.6 % of participants	31.4 % of participants

SECONDARY outcome

Timeframe: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).

Population: Full Analysis Set (All randomised patients)

Outcome measures

Outcome measures
Measure	Osimertinib 80mg n=279 Participants Daily single dose of Osimertinib 80mg	Chemotherapy n=140 Participants Platinum-based doublet chemotherapy
Duration of Response (DoR) by Investigator Assessment	9.7 months Interval 8.3 to 11.6	4.1 months Interval 3.0 to 5.6

SECONDARY outcome

Timeframe: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).

Population: Full Analysis Set (All randomised patients)

Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): \>= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions; Stable disease (SD): Neither sufficient shrinkage to qualify as a response nor sufficient growth to qualify as progression; Progressive Disease (PD): \>= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of \>=5mm (compared to the previous minimum sum) or progression of NTLs or a new lesion. DCR is the percentage of patients with best response of CR, PR or SD at \>=6 weeks, prior to any progressive disease (PD).

Outcome measures

Outcome measures
Measure	Osimertinib 80mg n=279 Participants Daily single dose of Osimertinib 80mg	Chemotherapy n=140 Participants Platinum-based doublet chemotherapy
Disease Control Rate (DCR) by Investigator Assessment	93.2 % of participants Interval 8.3 to 11.6	74.3 % of participants Interval 3.0 to 5.6

SECONDARY outcome

Timeframe: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).

Population: Full Analysis Set (All randomised patients)

Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Tumour size was calculated as the sum of the longest diameters (SLD) of the Target Lesions. Tumour shrinkage is percentage change in tumour size from baseline using RECIST v1.1 tumour response.

Outcome measures

Outcome measures
Measure	Osimertinib 80mg n=278 Participants Daily single dose of Osimertinib 80mg	Chemotherapy n=131 Participants Platinum-based doublet chemotherapy
Tumour Shrinkage by Investigator Assessment	-46.1 % change from baseline Standard Deviation 29.50	-24.4 % change from baseline Standard Deviation 29.27

SECONDARY outcome

Timeframe: From date of randomization until time of final OS analysis, a median follow-up of 43 months

Outcome measures

Outcome measures
Measure	Osimertinib 80mg n=279 Participants Daily single dose of Osimertinib 80mg	Chemotherapy n=140 Participants Platinum-based doublet chemotherapy
Secondary: Overall Survival (OS)	26.8 Months Interval 23.5 to 31.5	22.5 Months Interval 20.2 to 28.8

OTHER_PRE_SPECIFIED outcome

Timeframe: From date of randomisation until time of final OS analysis, a median follow-up of 43 months

Population: Full Analysis Set (All randomised patients)

Time from randomisation to first subsequent anti-cancer therapy (FST) following randomised treatment discontinuation, or death if no FST administered. Any patient not known to have died nor received any subsequent anti-cancer therapy (ST) was censored at the last time known not to have received ST, ie, the last follow-up visit this was confirmed.

Outcome measures

Outcome measures
Measure	Osimertinib 80mg n=279 Participants Daily single dose of Osimertinib 80mg	Chemotherapy n=140 Participants Platinum-based doublet chemotherapy
Time to First Subsequent Therapy (TFST)	16.0 Months Interval 13.8 to 18.4	6.0 Months Interval 5.2 to 6.9

OTHER_PRE_SPECIFIED outcome

Timeframe: From date of randomisation until time of final OS analysis, a median follow-up of 43 months

Population: Full Analysis set (All randomised patients)

Time from randomisation to second subsequent anti-cancer therapy (SST) following randomised treatment discontinuation, or death if no SST administered. Any patient not known to have died nor received any SST was censored at the last time known not to have received SST, ie, the last follow-up visit this was confirmed.

Outcome measures

Outcome measures
Measure	Osimertinib 80mg n=279 Participants Daily single dose of Osimertinib 80mg	Chemotherapy n=140 Participants Platinum-based doublet chemotherapy
Time to Second Subsequent Therapy (TSST)	20.0 Months Interval 17.2 to 23.2	19.0 Months Interval 16.5 to 22.0

Adverse Events

Osimertinib 80 mg

Serious events: 84 serious events

Other events: 275 other events

Deaths: 188 deaths

Chemotherapy

Serious events: 36 serious events

Other events: 134 other events

Deaths: 93 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 The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review, should the submission for publication be delayed in order to file patent application. The sponsor cannot require changes to the communication and cannot extend the embargo.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Osimertinib 80 mg n=279 participants at risk Daily single dose of Osimertinib 80mg	Chemotherapy n=136 participants at risk Platinum-based doublet chemotherapy
Blood and lymphatic system disorders Anaemia	0.36% 1/279 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	2.2% 3/136 • Number of events 3 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.00% 0/279 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.74% 1/136 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/279 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.74% 1/136 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Blood and lymphatic system disorders Leukocytosis	0.36% 1/279 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.00% 0/136 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Blood and lymphatic system disorders Leukopenia	0.00% 0/279 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.74% 1/136 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Blood and lymphatic system disorders Neutropenia	0.00% 0/279 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.74% 1/136 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Cardiac disorders Angina pectoris	0.00% 0/279 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.74% 1/136 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Cardiac disorders Atrial fibrillation	0.72% 2/279 • Number of events 2 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.74% 1/136 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Gastrointestinal disorders Intestinal ischaemia	0.36% 1/279 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.00% 0/136 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations Pneumonia	2.2% 6/279 • Number of events 6 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.00% 0/136 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Investigations Electrocardiogram QT prolonged	0.36% 1/279 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.00% 0/136 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Musculoskeletal and connective tissue disorders Back pain	0.72% 2/279 • Number of events 2 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.00% 0/136 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Nervous system disorders Epilepsy	0.00% 0/279 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	2.2% 3/136 • Number of events 3 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Nervous system disorders Seizure	0.36% 1/279 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.00% 0/136 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Respiratory, thoracic and mediastinal disorders Lung consolidation	0.36% 1/279 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.00% 0/136 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.72% 2/279 • Number of events 2 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.74% 1/136 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Vascular disorders Deep vein thrombosis	0.36% 1/279 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	2.9% 4/136 • Number of events 4 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Cardiac disorders Cardiac failure	0.72% 2/279 • Number of events 2 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.00% 0/136 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Cardiac disorders Pericardial effusion	0.36% 1/279 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.00% 0/136 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Ear and labyrinth disorders Vertigo	0.36% 1/279 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.74% 1/136 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Gastrointestinal disorders Ascites	0.00% 0/279 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.74% 1/136 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Gastrointestinal disorders Diarrhoea	0.36% 1/279 • Number of events 2 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.74% 1/136 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Gastrointestinal disorders Gastrointestinal disorder	0.00% 0/279 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.74% 1/136 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Gastrointestinal disorders Nausea	0.72% 2/279 • Number of events 2 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	1.5% 2/136 • Number of events 3 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Gastrointestinal disorders Vomiting	1.4% 4/279 • Number of events 4 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.74% 1/136 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
General disorders Asthenia	0.00% 0/279 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.74% 1/136 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
General disorders Chest discomfort	0.36% 1/279 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.00% 0/136 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
General disorders Non-cardiac chest pain	0.36% 1/279 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	1.5% 2/136 • Number of events 2 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
General disorders Pyrexia	0.72% 2/279 • Number of events 2 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	1.5% 2/136 • Number of events 2 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Immune system disorders Contrast media allergy	0.36% 1/279 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.00% 0/136 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations Bronchiolitis	0.36% 1/279 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.00% 0/136 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations Cellulitis	0.00% 0/279 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.74% 1/136 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations Enterocolitis infectious	0.36% 1/279 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.00% 0/136 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations Gastroenteritis	0.36% 1/279 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.00% 0/136 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations Hepatitis B	0.36% 1/279 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.00% 0/136 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations Herpes zoster	0.00% 0/279 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.74% 1/136 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations Lung infection	0.72% 2/279 • Number of events 2 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.00% 0/136 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations Pneumocystis jirovecii pneumonia	0.00% 0/279 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.74% 1/136 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations Pneumonia bacterial	0.36% 1/279 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.74% 1/136 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations Tuberculosis	0.36% 1/279 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	0.00% 0/136 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.

Other adverse events
Measure	Osimertinib 80 mg n=279 participants at risk Daily single dose of Osimertinib 80mg	Chemotherapy n=136 participants at risk Platinum-based doublet chemotherapy
Blood and lymphatic system disorders Anaemia	11.5% 32/279 • Number of events 38 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	25.7% 35/136 • Number of events 45 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Blood and lymphatic system disorders Leukopenia	5.0% 14/279 • Number of events 33 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	5.1% 7/136 • Number of events 12 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Blood and lymphatic system disorders Neutropenia	5.0% 14/279 • Number of events 24 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	12.5% 17/136 • Number of events 26 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Blood and lymphatic system disorders Thrombocytopenia	6.5% 18/279 • Number of events 30 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	7.4% 10/136 • Number of events 15 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Ear and labyrinth disorders Tinnitus	0.72% 2/279 • Number of events 2 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	5.1% 7/136 • Number of events 7 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Eye disorders Lacrimation increased	0.36% 1/279 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	5.9% 8/136 • Number of events 10 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Gastrointestinal disorders Abdominal pain upper	3.6% 10/279 • Number of events 13 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	8.1% 11/136 • Number of events 11 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Gastrointestinal disorders Constipation	17.9% 50/279 • Number of events 56 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	35.3% 48/136 • Number of events 94 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Gastrointestinal disorders Diarrhoea	44.1% 123/279 • Number of events 226 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	10.3% 14/136 • Number of events 21 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Gastrointestinal disorders Nausea	22.9% 64/279 • Number of events 75 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	48.5% 66/136 • Number of events 144 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Gastrointestinal disorders Stomatitis	17.2% 48/279 • Number of events 70 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	16.2% 22/136 • Number of events 26 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Gastrointestinal disorders Vomiting	15.1% 42/279 • Number of events 53 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	19.9% 27/136 • Number of events 49 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
General disorders Asthenia	8.2% 23/279 • Number of events 29 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	14.0% 19/136 • Number of events 25 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
General disorders Fatigue	19.4% 54/279 • Number of events 66 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	29.4% 40/136 • Number of events 60 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
General disorders Malaise	4.3% 12/279 • Number of events 14 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	10.3% 14/136 • Number of events 21 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
General disorders Non-cardiac chest pain	8.2% 23/279 • Number of events 24 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	4.4% 6/136 • Number of events 6 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
General disorders Oedema peripheral	5.7% 16/279 • Number of events 21 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	11.8% 16/136 • Number of events 23 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
General disorders Pyrexia	10.4% 29/279 • Number of events 36 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	9.6% 13/136 • Number of events 15 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations Nasopharyngitis	12.2% 34/279 • Number of events 45 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	5.1% 7/136 • Number of events 7 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations Paronychia	20.8% 58/279 • Number of events 72 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	1.5% 2/136 • Number of events 2 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations Upper respiratory tract infection	12.9% 36/279 • Number of events 61 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	7.4% 10/136 • Number of events 10 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations Urinary tract infection	8.6% 24/279 • Number of events 32 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	4.4% 6/136 • Number of events 9 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Investigations Alanine aminotransferase increased	8.2% 23/279 • Number of events 34 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	12.5% 17/136 • Number of events 25 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Investigations Aspartate aminotransferase increased	7.5% 21/279 • Number of events 33 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	11.8% 16/136 • Number of events 23 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Investigations Blood creatinine increased	5.7% 16/279 • Number of events 20 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	6.6% 9/136 • Number of events 15 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Investigations Neutrophil count decreased	6.1% 17/279 • Number of events 31 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	11.8% 16/136 • Number of events 38 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Investigations Platelet count decreased	7.2% 20/279 • Number of events 32 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	15.4% 21/136 • Number of events 34 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Investigations Weight decreased	5.7% 16/279 • Number of events 17 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	5.1% 7/136 • Number of events 7 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Investigations White blood cell count decreased	7.9% 22/279 • Number of events 38 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	8.8% 12/136 • Number of events 36 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Metabolism and nutrition disorders Decreased appetite	24.0% 67/279 • Number of events 78 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	36.0% 49/136 • Number of events 87 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Metabolism and nutrition disorders Hypoalbuminaemia	1.4% 4/279 • Number of events 6 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	5.1% 7/136 • Number of events 9 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Musculoskeletal and connective tissue disorders Arthralgia	9.0% 25/279 • Number of events 30 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	5.1% 7/136 • Number of events 8 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Musculoskeletal and connective tissue disorders Back pain	15.1% 42/279 • Number of events 52 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	10.3% 14/136 • Number of events 20 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	7.5% 21/279 • Number of events 25 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	5.9% 8/136 • Number of events 8 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Nervous system disorders Dizziness	7.9% 22/279 • Number of events 26 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	8.8% 12/136 • Number of events 16 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Nervous system disorders Dysgeusia	3.2% 9/279 • Number of events 9 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	8.8% 12/136 • Number of events 13 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Nervous system disorders Headache	11.8% 33/279 • Number of events 44 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	11.8% 16/136 • Number of events 19 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Psychiatric disorders Insomnia	9.3% 26/279 • Number of events 28 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	10.3% 14/136 • Number of events 16 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Respiratory, thoracic and mediastinal disorders Cough	21.5% 60/279 • Number of events 72 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	14.7% 20/136 • Number of events 21 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.
Respiratory, thoracic and mediastinal disorders Dyspnoea	12.5% 35/279 • Number of events 40 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.	13.2% 18/136 • Number of events 20 • AEs from start of study drug until 28 days post treatment discontinuation up to 4 years and 7 months (at the time of analysis) Systematic assessment due to regular investigator assessment at study visits.