Trial Outcomes & Findings for Efficacy and Safety of Selumetinib in Adults With NF1 Who Have Symptomatic, Inoperable Plexiform Neurofibromas (NCT NCT04924608)

NCT ID: NCT04924608

Last Updated: 2026-01-12

Results Overview

Objective response rate is defined as the proportion of participants who have a confirmed CR (defined as disappearance of the target PN, confirmed by a consecutive scan within 3 to 6 months after the first response) or confirmed PR (defined as a target PN volume decrease ≥ 20%, compared to baseline, confirmed by a consecutive scan within 3 to 6 months after the first response) by end of Cycle 16 as determined by ICR per REiNS criteria. Increase in the volume of the target PN by 20% or more compared to baseline or the time of best response after documenting a PR is considered as PD.

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE3
• Target enrollment: 145 participants
• Primary outcome timeframe: From first dose up until progression (if it occurs prior to the end of Cycle 16), or the last evaluable assessment up to and including the end of Cycle 16, excluding MRI during prolonged study intervention interruption (defined as interruption >= 28 days)
• Results posted on: 2026-01-12

Participant Flow

Participant milestones

Measure	Selumetinib 25 mg/m2 Actual Treatment Group	Placebo Actual Treatment Group
Overall Study STARTED	71	74
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	71	74

Reasons for withdrawal

Measure	Selumetinib 25 mg/m2 Actual Treatment Group	Placebo Actual Treatment Group
Overall Study Adverse Event	10	6
Overall Study Lost to Follow-up	1	1
Overall Study Ongoing at the data cut-off date	54	60
Overall Study Progressive Disease	2	0
Overall Study Withdrawal by Subject	3	6
Overall Study Other reason	1	1

Baseline Characteristics

Efficacy and Safety of Selumetinib in Adults With NF1 Who Have Symptomatic, Inoperable Plexiform Neurofibromas

Baseline characteristics by cohort

Measure	Selumetinib 25 mg/m2 n=71 Participants Actual Treatment Group	Placebo n=74 Participants Actual Treatment Group	Total n=145 Participants Total of all reporting groups
Age, Continuous	32.6 Years STANDARD_DEVIATION 11.42 • n=210 Participants	29.8 Years STANDARD_DEVIATION 8.72 • n=19 Participants	31.2 Years STANDARD_DEVIATION 10.19 • n=8 Participants
Sex: Female, Male Female	38 Participants n=210 Participants	32 Participants n=19 Participants	70 Participants n=8 Participants
Sex: Female, Male Male	33 Participants n=210 Participants	42 Participants n=19 Participants	75 Participants n=8 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=210 Participants	9 Participants n=19 Participants	14 Participants n=8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	63 Participants n=210 Participants	63 Participants n=19 Participants	126 Participants n=8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=210 Participants	2 Participants n=19 Participants	5 Participants n=8 Participants
Baseline PAINS-pNF chronic target PN pain intensity score Baseline PAINS-pNF chronic target PN pain intensity score >= 3	50 Participants n=210 Participants	53 Participants n=19 Participants	103 Participants n=8 Participants
Baseline PAINS-pNF chronic target PN pain intensity score Baseline PAINS-pNF chronic target PN pain intensity score < 3	21 Participants n=210 Participants	21 Participants n=19 Participants	42 Participants n=8 Participants
Height	163.517 cm STANDARD_DEVIATION 9.3702 • n=210 Participants	165.798 cm STANDARD_DEVIATION 12.2517 • n=19 Participants	164.698 cm STANDARD_DEVIATION 10.9784 • n=8 Participants
Weight	65.896 kg STANDARD_DEVIATION 15.9763 • n=210 Participants	66.271 kg STANDARD_DEVIATION 17.3971 • n=19 Participants	66.087 kg STANDARD_DEVIATION 16.6596 • n=8 Participants
BSA	1.713 m^2 STANDARD_DEVIATION 0.2319 • n=210 Participants	1.732 m^2 STANDARD_DEVIATION 0.2620 • n=19 Participants	1.722 m^2 STANDARD_DEVIATION 0.2471 • n=8 Participants
Geographical region China	11 count n=210 Participants	13 count n=19 Participants	24 count n=8 Participants
Geographical region Europe (includes France, Germany, Italy, Poland, Russia, Spain, and United Kingdom)	31 count n=210 Participants	30 count n=19 Participants	61 count n=8 Participants
Geographical region Japan	7 count n=210 Participants	8 count n=19 Participants	15 count n=8 Participants
Geographical region Rest of World (includes Australia, Brazil, Canada, and United States)	22 count n=210 Participants	23 count n=19 Participants	45 count n=8 Participants
Race Asian	22 Participants n=210 Participants	23 Participants n=19 Participants	45 Participants n=8 Participants
Race Black or African American	6 Participants n=210 Participants	3 Participants n=19 Participants	9 Participants n=8 Participants
Race White	38 Participants n=210 Participants	43 Participants n=19 Participants	81 Participants n=8 Participants
Race Other	2 Participants n=210 Participants	3 Participants n=19 Participants	5 Participants n=8 Participants
Race Not Reported	3 Participants n=210 Participants	2 Participants n=19 Participants	5 Participants n=8 Participants

PRIMARY outcome

Timeframe: From first dose up until progression (if it occurs prior to the end of Cycle 16), or the last evaluable assessment up to and including the end of Cycle 16, excluding MRI during prolonged study intervention interruption (defined as interruption >= 28 days)

Population: Full analysis set - All patients who are randomized to study intervention

Objective response rate is defined as the proportion of participants who have a confirmed CR (defined as disappearance of the target PN, confirmed by a consecutive scan within 3 to 6 months after the first response) or confirmed PR (defined as a target PN volume decrease ≥ 20%, compared to baseline, confirmed by a consecutive scan within 3 to 6 months after the first response) by end of Cycle 16 as determined by ICR per REiNS criteria.

Increase in the volume of the target PN by 20% or more compared to baseline or the time of best response after documenting a PR is considered as PD.

Outcome measures

Measure	Selumetinib 25 mg/m2 n=71 Participants Actual Treatment Group	Placebo n=74 Participants Actual Treatment Group
Confirmed Partial and Complete Response Rate (ORR) by End of Cycle 16 Using Volumetric MRI Analysis as Determined by ICR (Per REiNS Criteria) in Participants With NF1 Who Have Symptomatic, Inoperable PN.	19.7 Percentage Interval 11.2 to 30.9	5.4 Percentage Interval 1.5 to 13.3

SECONDARY outcome

Timeframe: Baseline and end of cycle 12 of study intervention

Population: Pain full analysis set - subjects randomised to study intervention with a baseline PAINS-pNF chronic target PN pain intensity score \>= 3.

The PAINS-pNF (Pain Intensity Scale for Plexiform Neurofibroma) chronic target PN pain intensity measures the participants' experience of chronic PN-related pain intensity with score from 0 (no chronic tumor pain) to 10 (worst chronic tumor pain). Baseline PAINS-pNF chronic target PN pain score is defined as the average of the available daily PAINS-pNF chronic target PN pain scores in the screening perio, while for Cycle 12, it is defined as the average of the available daily scores for the 28-days cycle up to and including the last day assessment of cycle 12. The difference of the means in the change from baseline at Cycle 12 between selumetinib and placebo in participants with a PAINS-pNF chronic target PN pain score of ≥ 3 at baseline is presented.

Outcome measures

Measure	Selumetinib 25 mg/m2 n=42 Participants Actual Treatment Group	Placebo n=42 Participants Actual Treatment Group
(First Key Secondary) The Difference of the Means in the Change From Baseline in PAINS-pNF Chronic Target PN Pain Intensity Score at Cycle 12 Between Selumetinib and Placebo, Primary Analysis	-2.0 Scores on a scale Standard Error 0.30	-1.3 Scores on a scale Standard Error 0.29

SECONDARY outcome

Timeframe: Baseline and end of cycle 12 of study intervention

Population: Full analysis set - subjects randomised to study intervention

The PAINS-pNF (Pain Intensity Scale for Plexiform Neurofibroma) chronic target PN pain intensity measures the participants' experience of chronic PN-related pain intensity with score from 0 (no chronic tumor pain) to 10 (worst chronic tumor pain). Baseline PAINS-pNF chronic target PN pain score is defined as the average of the available daily PAINS-pNF chronic target PN pain scores in the screening perio, while for Cycle 12, it is defined as the average of the available daily scores for the 28-days cycle up to and including the last day assessment of cycle 12. The difference of the means in the change from baseline at Cycle 12 between selumetinib and placebo participants is presented.

Outcome measures

Measure	Selumetinib 25 mg/m2 n=57 Participants Actual Treatment Group	Placebo n=62 Participants Actual Treatment Group
(First Key Secondary) The Difference of the Means in the Change From Baseline in PAINS-pNF Chronic Target PN Pain Intensity Score at Cycle 12 Between Selumetinib and Placebo, Supplemental Analysis	-1.6 Scores on a scale Standard Error 0.22	-0.9 Scores on a scale Standard Error 0.21

SECONDARY outcome

Timeframe: Baseline and end of Cycle 12 of study intervention

Population: Full analysis set - subjects randomised to study intervention

PlexiQoL (Plexiform Neurofibroma Quality of Life scale) is a patient-derived QoL measure specific to adults with NF1-associated PNs. It assesses the impact of PNs on patients' ability to fulfil their human needs. The measure consists of 18 dichotomous items with 0 =Not True and 1 = True. PlexiQoL total scores were calculated by the sum of all items to a maximum of 18, with lower scores indicating better quality of life. The change from baseline to the end of each cycle in PlexiQoL total score was derived as the PlexiQoL total score at the cycle 12 minus baseline PlexiQoL total score and presented.

Outcome measures

Measure	Selumetinib 25 mg/m2 n=57 Participants Actual Treatment Group	Placebo n=59 Participants Actual Treatment Group
(Second Key Secondary Endpoint) The Difference of the Means in the Change From Baseline in PlexiQoL Total Score at Cycle 12	-0.4 Scores on a scale Standard Error 0.45	-0.3 Scores on a scale Standard Error 0.44

Adverse Events

Selumetinib 25 mg/m2

Serious events: 10 serious events

Other events: 70 other events

Deaths: 0 deaths

Placebo

Serious events: 9 serious events

Other events: 54 other events

Deaths: 0 deaths

Serious adverse events

Measure	Selumetinib 25 mg/m2 n=71 participants at risk Actual Treatment Group	Placebo n=74 participants at risk Actual Treatment Group
Infections and infestations Cellulitis	2.8% 2/71 • Number of events 2 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	0.00% 0/74 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Infections and infestations Pneumonia	1.4% 1/71 • Number of events 2 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	0.00% 0/74 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Infections and infestations Urinary tract infection bacterial	0.00% 0/71 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	1.4% 1/74 • Number of events 1 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Injury, poisoning and procedural complications Accident	0.00% 0/71 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	1.4% 1/74 • Number of events 1 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Injury, poisoning and procedural complications Joint dislocation	1.4% 1/71 • Number of events 1 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	0.00% 0/74 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/71 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	1.4% 1/74 • Number of events 1 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neurofibrosarcoma	1.4% 1/71 • Number of events 1 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	4.1% 3/74 • Number of events 3 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neurofibrosarcoma recurrent	1.4% 1/71 • Number of events 1 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	0.00% 0/74 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Nervous system disorders Headache	1.4% 1/71 • Number of events 2 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	0.00% 0/74 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Nervous system disorders Paraparesis	1.4% 1/71 • Number of events 1 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	0.00% 0/74 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Nervous system disorders Seizure	0.00% 0/71 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	1.4% 1/74 • Number of events 1 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Psychiatric disorders Psychiatric decompensation	1.4% 1/71 • Number of events 1 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	0.00% 0/74 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Renal and urinary disorders Nephrolithiasis	0.00% 0/71 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	1.4% 1/74 • Number of events 2 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/71 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	1.4% 1/74 • Number of events 1 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.4% 1/71 • Number of events 1 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	0.00% 0/74 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Gastrointestinal disorders Dental caries	0.00% 0/71 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	1.4% 1/74 • Number of events 1 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.

Other adverse events

Measure	Selumetinib 25 mg/m2 n=71 participants at risk Actual Treatment Group	Placebo n=74 participants at risk Actual Treatment Group
Gastrointestinal disorders Vomiting	25.4% 18/71 • Number of events 33 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	8.1% 6/74 • Number of events 7 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
General disorders Fatigue	19.7% 14/71 • Number of events 14 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	13.5% 10/74 • Number of events 10 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
General disorders Oedema peripheral	15.5% 11/71 • Number of events 14 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	1.4% 1/74 • Number of events 1 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
General disorders Pyrexia	7.0% 5/71 • Number of events 6 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	4.1% 3/74 • Number of events 3 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Infections and infestations Covid-19	15.5% 11/71 • Number of events 12 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	20.3% 15/74 • Number of events 16 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Infections and infestations Paronychia	12.7% 9/71 • Number of events 9 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	4.1% 3/74 • Number of events 3 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Infections and infestations Upper respiratory tract infection	7.0% 5/71 • Number of events 7 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	6.8% 5/74 • Number of events 6 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Blood and lymphatic system disorders Anaemia	7.0% 5/71 • Number of events 6 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	10.8% 8/74 • Number of events 10 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Investigations Alanine aminotransferase increased	15.5% 11/71 • Number of events 12 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	6.8% 5/74 • Number of events 6 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Investigations Aspartate aminotransferase increased	18.3% 13/71 • Number of events 17 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	5.4% 4/74 • Number of events 5 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Investigations Blood creatine phosphokinase increased	45.1% 32/71 • Number of events 40 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	5.4% 4/74 • Number of events 6 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Investigations Ejection fraction decreased	7.0% 5/71 • Number of events 5 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	2.7% 2/74 • Number of events 3 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Investigations Protein urine present	0.00% 0/71 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	5.4% 4/74 • Number of events 5 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Investigations Weight increased	5.6% 4/71 • Number of events 4 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	4.1% 3/74 • Number of events 3 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Metabolism and nutrition disorders Decreased appetite	1.4% 1/71 • Number of events 1 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	9.5% 7/74 • Number of events 7 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Psychiatric disorders Insomnia	5.6% 4/71 • Number of events 4 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	0.00% 0/74 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Musculoskeletal and connective tissue disorders Arthralgia	4.2% 3/71 • Number of events 3 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	10.8% 8/74 • Number of events 8 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Gastrointestinal disorders Abdominal pain	8.5% 6/71 • Number of events 8 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	5.4% 4/74 • Number of events 4 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Musculoskeletal and connective tissue disorders Back pain	7.0% 5/71 • Number of events 5 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	1.4% 1/74 • Number of events 1 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Musculoskeletal and connective tissue disorders Myalgia	5.6% 4/71 • Number of events 4 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	1.4% 1/74 • Number of events 1 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Musculoskeletal and connective tissue disorders Pain in extremity	7.0% 5/71 • Number of events 6 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	10.8% 8/74 • Number of events 9 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Nervous system disorders Headache	9.9% 7/71 • Number of events 8 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	12.2% 9/74 • Number of events 18 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Gastrointestinal disorders Constipation	9.9% 7/71 • Number of events 7 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	1.4% 1/74 • Number of events 2 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Respiratory, thoracic and mediastinal disorders Cough	5.6% 4/71 • Number of events 4 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	5.4% 4/74 • Number of events 4 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.6% 4/71 • Number of events 4 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	2.7% 2/74 • Number of events 2 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Skin and subcutaneous tissue disorders Acne	7.0% 5/71 • Number of events 6 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	0.00% 0/74 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Skin and subcutaneous tissue disorders Alopecia	18.3% 13/71 • Number of events 14 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	10.8% 8/74 • Number of events 8 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Skin and subcutaneous tissue disorders Dermatitis acneiform	59.2% 42/71 • Number of events 49 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	10.8% 8/74 • Number of events 9 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Skin and subcutaneous tissue disorders Dry skin	18.3% 13/71 • Number of events 15 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	5.4% 4/74 • Number of events 5 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Skin and subcutaneous tissue disorders Pruritus	9.9% 7/71 • Number of events 7 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	6.8% 5/74 • Number of events 7 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Skin and subcutaneous tissue disorders Rash	15.5% 11/71 • Number of events 16 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	4.1% 3/74 • Number of events 3 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Skin and subcutaneous tissue disorders Rash maculo-papular	5.6% 4/71 • Number of events 4 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	1.4% 1/74 • Number of events 1 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Gastrointestinal disorders Diarrhoea	42.3% 30/71 • Number of events 50 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	12.2% 9/74 • Number of events 9 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Gastrointestinal disorders Dry mouth	7.0% 5/71 • Number of events 5 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	2.7% 2/74 • Number of events 2 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Gastrointestinal disorders Nausea	25.4% 18/71 • Number of events 19 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	16.2% 12/74 • Number of events 14 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.
Gastrointestinal disorders Stomatitis	9.9% 7/71 • Number of events 8 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.	4.1% 3/74 • Number of events 3 • All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group. All-cause mortality was reported for all subjects. Adverse events were reported for subjects who received at least one dose of study drug and include AEs that start prior to and worsen after treatment or with an onset or worsening date on or after the date of first selumetinib dose up to and including 30 days after the date of last selumetinib dose. All TESAE, and non-serious TEAEs for a preferred term at a frequency of \> 5% in any treatment group during the randomized period are presented.

Additional Information

Global Clinical Lead

AstraZeneca Clinical Study Information Center

Phone: 1-877-240-9479

Email: information.center@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place