Trial Outcomes & Findings for Radiation Therapy With or Without Chemotherapy in Patients With Stage I-IIA Cervical Cancer Who Previously Underwent Surgery (NCT NCT01101451)

Last Updated: 2025-05-23

Results Overview

Estimate for probability of RFS at 3 years using Kaplan-Meier method, where RFS is defined as time from protocol registration (and randomization) to the date of first documented recurrence, death, or the date of last contact, whichever occurs first. Patients without recurrence or death were censored at the date of last contact.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

340 participants

Primary outcome timeframe

3 years from randomization

Results posted on

2025-05-23

Participant Flow

GOG-0263 opened to accrual on April 12, 2010, and closed to accrual on April 11, 2022.

Participant milestones

Participant milestones
Measure	Arm I (Radiation) Patients undergo pelvic external-beam radiation therapy (EBRT) or intensity-modulated radiation therapy (IMRT) 5 days a week for 5.5 weeks.	Arm II (Cisplatin + Radiation) Patients receive cisplatin IV over 1-2 hours on day 1 and undergo radiotherapy as in Arm I. Treatment with cisplatin repeats every 7 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	172	168
Overall Study COMPLETED	158	153
Overall Study NOT COMPLETED	14	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm I (Radiation) Patients undergo pelvic external-beam radiation therapy (EBRT) or intensity-modulated radiation therapy (IMRT) 5 days a week for 5.5 weeks.	Arm II (Cisplatin + Radiation) Patients receive cisplatin IV over 1-2 hours on day 1 and undergo radiotherapy as in Arm I. Treatment with cisplatin repeats every 7 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Overall Study Eligible and never treated	0	5
Overall Study Ineligible and treated	12	8
Overall Study Ineligible and never treated	2	2

Baseline Characteristics

Radiation Therapy With or Without Chemotherapy in Patients With Stage I-IIA Cervical Cancer Who Previously Underwent Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (Radiation) n=158 Participants Patients undergo pelvic external-beam radiation therapy (EBRT) or intensity-modulated radiation therapy (IMRT) 5 days a week for 5.5 weeks.	Arm II (Cisplatin + Radiation) n=158 Participants Patients receive cisplatin IV over 1-2 hours on day 1 and undergo radiotherapy as in Arm I. Treatment with cisplatin repeats every 7 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	Total n=316 Participants Total of all reporting groups
Age, Customized 20-29 years	3 Participants n=99 Participants	2 Participants n=107 Participants	5 Participants n=206 Participants
Age, Customized 30-39 years	28 Participants n=99 Participants	47 Participants n=107 Participants	75 Participants n=206 Participants
Age, Customized 40-49 years	62 Participants n=99 Participants	53 Participants n=107 Participants	115 Participants n=206 Participants
Age, Customized 50-59 years	46 Participants n=99 Participants	33 Participants n=107 Participants	79 Participants n=206 Participants
Age, Customized 60-69 years	13 Participants n=99 Participants	17 Participants n=107 Participants	30 Participants n=206 Participants
Age, Customized 70-79 years	5 Participants n=99 Participants	6 Participants n=107 Participants	11 Participants n=206 Participants
Age, Customized >= 80 years	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Sex: Female, Male Female	158 Participants n=99 Participants	158 Participants n=107 Participants	316 Participants n=206 Participants
Sex: Female, Male Male	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	12 Participants n=99 Participants	15 Participants n=107 Participants	27 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	142 Participants n=99 Participants	142 Participants n=107 Participants	284 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=99 Participants	1 Participants n=107 Participants	5 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=99 Participants	2 Participants n=107 Participants	4 Participants n=206 Participants
Race (NIH/OMB) Asian	79 Participants n=99 Participants	87 Participants n=107 Participants	166 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Black or African American	12 Participants n=99 Participants	5 Participants n=107 Participants	17 Participants n=206 Participants
Race (NIH/OMB) White	62 Participants n=99 Participants	58 Participants n=107 Participants	120 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=99 Participants	6 Participants n=107 Participants	8 Participants n=206 Participants

PRIMARY outcome

Timeframe: 3 years from randomization

Population: Eligible participants

Outcome measures

Outcome measures
Measure	Arm I (Radiation) n=158 Participants Patients undergo pelvic external-beam radiation therapy (EBRT) or intensity-modulated radiation therapy (IMRT) 5 days a week for 5.5 weeks.	Arm II (Cisplatin + Radiation) n=158 Participants Patients receive cisplatin IV over 1-2 hours on day 1 and undergo radiotherapy as in Arm I. Treatment with cisplatin repeats every 7 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Recurrence-free Survival (RFS) Rate at 3-years	85.4 percentage of participants Interval 79.0 to 90.0	88.5 percentage of participants Interval 82.0 to 93.0

SECONDARY outcome

Timeframe: 3 years from randomization

Population: Eligible participants

Estimate for probability of overall survival at 3 years by Kaplan-Meier method, where overall survival is defined as the time from randomization to time of death due to any cause or the date of last contact, whichever occurs first.

Outcome measures

Outcome measures
Measure	Arm I (Radiation) n=158 Participants Patients undergo pelvic external-beam radiation therapy (EBRT) or intensity-modulated radiation therapy (IMRT) 5 days a week for 5.5 weeks.	Arm II (Cisplatin + Radiation) n=158 Participants Patients receive cisplatin IV over 1-2 hours on day 1 and undergo radiotherapy as in Arm I. Treatment with cisplatin repeats every 7 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Overall Survival (OS) Rate at 3-years	90.3 percentage of participants Interval 84.0 to 94.0	97.2 percentage of participants Interval 93.0 to 99.0

SECONDARY outcome

Timeframe: During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days.

Population: Randomized participants who received any assigned protocol therapy

Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v4.0.

Outcome measures

Outcome measures
Measure	Arm I (Radiation) n=170 Participants Patients undergo pelvic external-beam radiation therapy (EBRT) or intensity-modulated radiation therapy (IMRT) 5 days a week for 5.5 weeks.	Arm II (Cisplatin + Radiation) n=161 Participants Patients receive cisplatin IV over 1-2 hours on day 1 and undergo radiotherapy as in Arm I. Treatment with cisplatin repeats every 7 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. Anemia	1 Participants	6 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. Other blood/lymphatics	0 Participants	4 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. White blood cell decreased	3 Participants	45 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. Platelet count decreased	0 Participants	4 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. Neutrophil count decreased	2 Participants	27 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. Other investigations	7 Participants	8 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. Gastrointestinal	10 Participants	12 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. General and administration site	2 Participants	3 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. Infections/infestations	4 Participants	4 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. Metabolism/nutrition	0 Participants	7 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. Musculoskeletal/connective tissue	1 Participants	0 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. Nervous system	2 Participants	1 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. Psychiatric	1 Participants	1 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. Renal/urinary	2 Participants	2 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. Reproductive/breast	2 Participants	1 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. Skin/subcutaneous	0 Participants	3 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. Vascular disorders	0 Participants	1 Participants

SECONDARY outcome

Timeframe: up to 11 years

Population: Per protocol, patient risk-benefit will be assessed only for a positive study. Based on the results information at the specified significance level, patient risk-benefit was not assessed as pre-specified

The reporting group (2) did not demonstrate improved RFS compared to the reporting group (1) at the pre-specified significance level. Per the protocol, patient risk-benefit will be assessed only for a positive study. This is not assessed due to non-positive study per the protocol.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1. Pre-treatment (baseline), 2. 3 weeks following the first day of treatment, 3. 7 weeks following the first day of treatment, 4. 36 weeks following the first day of treatment.

Population: Eligible patients who completed baseline and at lease one follow-up QOL assessments.

The patient-reported QOL is assessed with the Trial Outcome Index of the Functional Assessment of Cancer Therapy-Cervix (FACT-Cx TOI). The FACT-Cx TOI is ranged 0-116 and a larger FACT-Cx TOI score suggests a favorable QoL.

Outcome measures

Outcome measures
Measure	Arm I (Radiation) n=152 Participants Patients undergo pelvic external-beam radiation therapy (EBRT) or intensity-modulated radiation therapy (IMRT) 5 days a week for 5.5 weeks.	Arm II (Cisplatin + Radiation) n=147 Participants Patients receive cisplatin IV over 1-2 hours on day 1 and undergo radiotherapy as in Arm I. Treatment with cisplatin repeats every 7 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Quality of Life (QOL) as Measured With the FACT-Cx TOI Baseline	83.5 units on a scale Standard Deviation 15.4	80.1 units on a scale Standard Deviation 15.4
Quality of Life (QOL) as Measured With the FACT-Cx TOI 3 weeks	79.0 units on a scale Standard Deviation 16.4	71.4 units on a scale Standard Deviation 15.3
Quality of Life (QOL) as Measured With the FACT-Cx TOI 7 weeks	80.1 units on a scale Standard Deviation 17.0	71.8 units on a scale Standard Deviation 17.1
Quality of Life (QOL) as Measured With the FACT-Cx TOI 36 weeks	88.8 units on a scale Standard Deviation 15.5	88.1 units on a scale Standard Deviation 12.3

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 11 years

Assessed by the number of cycles and amount of chemoradiotherapy administered, treatment span, incidence and duration of treatment delays, reason for delays, and reason why off study therapy.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 11 years

The site(s) of first disease recurrence will be classified as: pelvic-only, extra-pelvic-only or pelvic-and-extra-pelvic and tabulated by treatment group. The test of the hypothesis that the probability of local failure is independent of randomized treatment will be assessed with exact logistic regression adjusted know prognostic factors.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 11 years

Assessed with Exact Logistic Regression adjusted known prognostic factors.

Outcome measures

Outcome data not reported

Adverse Events

Arm I (Radiation)

Serious events: 7 serious events

Other events: 140 other events

Deaths: 20 deaths

Arm II (Cisplatin + Radiation)

Serious events: 9 serious events

Other events: 158 other events

Deaths: 12 deaths

Serious adverse events

Other adverse events

Additional Information

Helen Huang on behalf of Wei Deng Ph.D.

NRG Oncology

Phone: 7168452318

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Arm I (Radiation) n=170 participants at risk Patients undergo pelvic external-beam radiation therapy (EBRT) or intensity-modulated radiation therapy (IMRT) 5 days a week for 5.5 weeks.	Arm II (Cisplatin + Radiation) n=161 participants at risk Patients receive cisplatin IV over 1-2 hours on day 1 and undergo radiotherapy as in Arm I. Treatment with cisplatin repeats every 7 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Blood And Lymphatic System Disorders - Other	0.00% 0/170 • During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days. All randomized participants who received any assigned protocol therapy were monitored/assessed for serious adverse events and other adverse events. Randomized eligible participants were monitored/assessed for All-Cause Mortality. The All-Cause Mortality that occurred from randomization until 54 RFS events have occurred with a median follow-up 76.5 months (inter-quartile range: 50.3 to 107.7 months) estimated by reverse Kaplan-Meier method.	0.62% 1/161 • During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days. All randomized participants who received any assigned protocol therapy were monitored/assessed for serious adverse events and other adverse events. Randomized eligible participants were monitored/assessed for All-Cause Mortality. The All-Cause Mortality that occurred from randomization until 54 RFS events have occurred with a median follow-up 76.5 months (inter-quartile range: 50.3 to 107.7 months) estimated by reverse Kaplan-Meier method.
Gastrointestinal disorders Colonic Fistula	0.59% 1/170 • During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days. All randomized participants who received any assigned protocol therapy were monitored/assessed for serious adverse events and other adverse events. Randomized eligible participants were monitored/assessed for All-Cause Mortality. The All-Cause Mortality that occurred from randomization until 54 RFS events have occurred with a median follow-up 76.5 months (inter-quartile range: 50.3 to 107.7 months) estimated by reverse Kaplan-Meier method.	0.00% 0/161 • During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days. All randomized participants who received any assigned protocol therapy were monitored/assessed for serious adverse events and other adverse events. Randomized eligible participants were monitored/assessed for All-Cause Mortality. The All-Cause Mortality that occurred from randomization until 54 RFS events have occurred with a median follow-up 76.5 months (inter-quartile range: 50.3 to 107.7 months) estimated by reverse Kaplan-Meier method.
Gastrointestinal disorders Vomiting	0.00% 0/170 • During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days. All randomized participants who received any assigned protocol therapy were monitored/assessed for serious adverse events and other adverse events. Randomized eligible participants were monitored/assessed for All-Cause Mortality. The All-Cause Mortality that occurred from randomization until 54 RFS events have occurred with a median follow-up 76.5 months (inter-quartile range: 50.3 to 107.7 months) estimated by reverse Kaplan-Meier method.	0.62% 1/161 • During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days. All randomized participants who received any assigned protocol therapy were monitored/assessed for serious adverse events and other adverse events. Randomized eligible participants were monitored/assessed for All-Cause Mortality. The All-Cause Mortality that occurred from randomization until 54 RFS events have occurred with a median follow-up 76.5 months (inter-quartile range: 50.3 to 107.7 months) estimated by reverse Kaplan-Meier method.
Gastrointestinal disorders Abdominal Pain	0.59% 1/170 • During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days. All randomized participants who received any assigned protocol therapy were monitored/assessed for serious adverse events and other adverse events. Randomized eligible participants were monitored/assessed for All-Cause Mortality. The All-Cause Mortality that occurred from randomization until 54 RFS events have occurred with a median follow-up 76.5 months (inter-quartile range: 50.3 to 107.7 months) estimated by reverse Kaplan-Meier method.	0.00% 0/161 • During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days. All randomized participants who received any assigned protocol therapy were monitored/assessed for serious adverse events and other adverse events. Randomized eligible participants were monitored/assessed for All-Cause Mortality. The All-Cause Mortality that occurred from randomization until 54 RFS events have occurred with a median follow-up 76.5 months (inter-quartile range: 50.3 to 107.7 months) estimated by reverse Kaplan-Meier method.
Gastrointestinal disorders Nausea	0.00% 0/170 • During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days. All randomized participants who received any assigned protocol therapy were monitored/assessed for serious adverse events and other adverse events. Randomized eligible participants were monitored/assessed for All-Cause Mortality. The All-Cause Mortality that occurred from randomization until 54 RFS events have occurred with a median follow-up 76.5 months (inter-quartile range: 50.3 to 107.7 months) estimated by reverse Kaplan-Meier method.	1.2% 2/161 • During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days. All randomized participants who received any assigned protocol therapy were monitored/assessed for serious adverse events and other adverse events. Randomized eligible participants were monitored/assessed for All-Cause Mortality. The All-Cause Mortality that occurred from randomization until 54 RFS events have occurred with a median follow-up 76.5 months (inter-quartile range: 50.3 to 107.7 months) estimated by reverse Kaplan-Meier method.
Infections and infestations Infections And Infestations - Other	0.59% 1/170 • During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days. All randomized participants who received any assigned protocol therapy were monitored/assessed for serious adverse events and other adverse events. Randomized eligible participants were monitored/assessed for All-Cause Mortality. The All-Cause Mortality that occurred from randomization until 54 RFS events have occurred with a median follow-up 76.5 months (inter-quartile range: 50.3 to 107.7 months) estimated by reverse Kaplan-Meier method.	0.00% 0/161 • During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days. All randomized participants who received any assigned protocol therapy were monitored/assessed for serious adverse events and other adverse events. Randomized eligible participants were monitored/assessed for All-Cause Mortality. The All-Cause Mortality that occurred from randomization until 54 RFS events have occurred with a median follow-up 76.5 months (inter-quartile range: 50.3 to 107.7 months) estimated by reverse Kaplan-Meier method.
Infections and infestations Kidney Infection	0.59% 1/170 • During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days. All randomized participants who received any assigned protocol therapy were monitored/assessed for serious adverse events and other adverse events. Randomized eligible participants were monitored/assessed for All-Cause Mortality. The All-Cause Mortality that occurred from randomization until 54 RFS events have occurred with a median follow-up 76.5 months (inter-quartile range: 50.3 to 107.7 months) estimated by reverse Kaplan-Meier method.	0.00% 0/161 • During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days. All randomized participants who received any assigned protocol therapy were monitored/assessed for serious adverse events and other adverse events. Randomized eligible participants were monitored/assessed for All-Cause Mortality. The All-Cause Mortality that occurred from randomization until 54 RFS events have occurred with a median follow-up 76.5 months (inter-quartile range: 50.3 to 107.7 months) estimated by reverse Kaplan-Meier method.
Investigations White Blood Cell Decreased	0.00% 0/170 • During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days. All randomized participants who received any assigned protocol therapy were monitored/assessed for serious adverse events and other adverse events. Randomized eligible participants were monitored/assessed for All-Cause Mortality. The All-Cause Mortality that occurred from randomization until 54 RFS events have occurred with a median follow-up 76.5 months (inter-quartile range: 50.3 to 107.7 months) estimated by reverse Kaplan-Meier method.	1.2% 2/161 • During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days. All randomized participants who received any assigned protocol therapy were monitored/assessed for serious adverse events and other adverse events. Randomized eligible participants were monitored/assessed for All-Cause Mortality. The All-Cause Mortality that occurred from randomization until 54 RFS events have occurred with a median follow-up 76.5 months (inter-quartile range: 50.3 to 107.7 months) estimated by reverse Kaplan-Meier method.
Metabolism and nutrition disorders Hypomagnesemia	0.00% 0/170 • During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days. All randomized participants who received any assigned protocol therapy were monitored/assessed for serious adverse events and other adverse events. Randomized eligible participants were monitored/assessed for All-Cause Mortality. The All-Cause Mortality that occurred from randomization until 54 RFS events have occurred with a median follow-up 76.5 months (inter-quartile range: 50.3 to 107.7 months) estimated by reverse Kaplan-Meier method.	0.62% 1/161 • During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days. All randomized participants who received any assigned protocol therapy were monitored/assessed for serious adverse events and other adverse events. Randomized eligible participants were monitored/assessed for All-Cause Mortality. The All-Cause Mortality that occurred from randomization until 54 RFS events have occurred with a median follow-up 76.5 months (inter-quartile range: 50.3 to 107.7 months) estimated by reverse Kaplan-Meier method.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/170 • During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days. All randomized participants who received any assigned protocol therapy were monitored/assessed for serious adverse events and other adverse events. Randomized eligible participants were monitored/assessed for All-Cause Mortality. The All-Cause Mortality that occurred from randomization until 54 RFS events have occurred with a median follow-up 76.5 months (inter-quartile range: 50.3 to 107.7 months) estimated by reverse Kaplan-Meier method.	0.62% 1/161 • During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days. All randomized participants who received any assigned protocol therapy were monitored/assessed for serious adverse events and other adverse events. Randomized eligible participants were monitored/assessed for All-Cause Mortality. The All-Cause Mortality that occurred from randomization until 54 RFS events have occurred with a median follow-up 76.5 months (inter-quartile range: 50.3 to 107.7 months) estimated by reverse Kaplan-Meier method.
Musculoskeletal and connective tissue disorders Chest Wall Pain	0.59% 1/170 • During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days. All randomized participants who received any assigned protocol therapy were monitored/assessed for serious adverse events and other adverse events. Randomized eligible participants were monitored/assessed for All-Cause Mortality. The All-Cause Mortality that occurred from randomization until 54 RFS events have occurred with a median follow-up 76.5 months (inter-quartile range: 50.3 to 107.7 months) estimated by reverse Kaplan-Meier method.	0.00% 0/161 • During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days. All randomized participants who received any assigned protocol therapy were monitored/assessed for serious adverse events and other adverse events. Randomized eligible participants were monitored/assessed for All-Cause Mortality. The All-Cause Mortality that occurred from randomization until 54 RFS events have occurred with a median follow-up 76.5 months (inter-quartile range: 50.3 to 107.7 months) estimated by reverse Kaplan-Meier method.
Nervous system disorders Seizure	0.00% 0/170 • During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days. All randomized participants who received any assigned protocol therapy were monitored/assessed for serious adverse events and other adverse events. Randomized eligible participants were monitored/assessed for All-Cause Mortality. The All-Cause Mortality that occurred from randomization until 54 RFS events have occurred with a median follow-up 76.5 months (inter-quartile range: 50.3 to 107.7 months) estimated by reverse Kaplan-Meier method.	0.62% 1/161 • During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days. All randomized participants who received any assigned protocol therapy were monitored/assessed for serious adverse events and other adverse events. Randomized eligible participants were monitored/assessed for All-Cause Mortality. The All-Cause Mortality that occurred from randomization until 54 RFS events have occurred with a median follow-up 76.5 months (inter-quartile range: 50.3 to 107.7 months) estimated by reverse Kaplan-Meier method.
Psychiatric disorders Suicidal Ideation	0.59% 1/170 • During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days. All randomized participants who received any assigned protocol therapy were monitored/assessed for serious adverse events and other adverse events. Randomized eligible participants were monitored/assessed for All-Cause Mortality. The All-Cause Mortality that occurred from randomization until 54 RFS events have occurred with a median follow-up 76.5 months (inter-quartile range: 50.3 to 107.7 months) estimated by reverse Kaplan-Meier method.	0.00% 0/161 • During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days. All randomized participants who received any assigned protocol therapy were monitored/assessed for serious adverse events and other adverse events. Randomized eligible participants were monitored/assessed for All-Cause Mortality. The All-Cause Mortality that occurred from randomization until 54 RFS events have occurred with a median follow-up 76.5 months (inter-quartile range: 50.3 to 107.7 months) estimated by reverse Kaplan-Meier method.
Renal and urinary disorders Urinary Tract Obstruction	0.59% 1/170 • During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days. All randomized participants who received any assigned protocol therapy were monitored/assessed for serious adverse events and other adverse events. Randomized eligible participants were monitored/assessed for All-Cause Mortality. The All-Cause Mortality that occurred from randomization until 54 RFS events have occurred with a median follow-up 76.5 months (inter-quartile range: 50.3 to 107.7 months) estimated by reverse Kaplan-Meier method.	0.62% 1/161 • During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days. All randomized participants who received any assigned protocol therapy were monitored/assessed for serious adverse events and other adverse events. Randomized eligible participants were monitored/assessed for All-Cause Mortality. The All-Cause Mortality that occurred from randomization until 54 RFS events have occurred with a median follow-up 76.5 months (inter-quartile range: 50.3 to 107.7 months) estimated by reverse Kaplan-Meier method.
Reproductive system and breast disorders Vaginal Pain	0.59% 1/170 • During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days. All randomized participants who received any assigned protocol therapy were monitored/assessed for serious adverse events and other adverse events. Randomized eligible participants were monitored/assessed for All-Cause Mortality. The All-Cause Mortality that occurred from randomization until 54 RFS events have occurred with a median follow-up 76.5 months (inter-quartile range: 50.3 to 107.7 months) estimated by reverse Kaplan-Meier method.	0.00% 0/161 • During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days. All randomized participants who received any assigned protocol therapy were monitored/assessed for serious adverse events and other adverse events. Randomized eligible participants were monitored/assessed for All-Cause Mortality. The All-Cause Mortality that occurred from randomization until 54 RFS events have occurred with a median follow-up 76.5 months (inter-quartile range: 50.3 to 107.7 months) estimated by reverse Kaplan-Meier method.