Tisotumab Vedotin vs Chemotherapy in Recurrent or Metastatic Cervical Cancer

Overall survival is defined as the time from the date of randomization to the date of death due to any cause. In the absence of confirmation of death, survival time was censored at the last date the participant was known to be alive.

Time frame: From randomization to date of death due to any cause or censoring date, whichever occurred first (maximum up to 25 months)

Population: ITT analysis set included all randomized participants. Participants were included in the treatment group assigned at randomization regardless of any actual treatment received.

Confirmed objective response rate was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) per RECIST v.1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR was defined as at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The minimum criteria for stable disease (SD) duration are defined as ≥ 5 weeks after the date of randomization. For a response to be considered as confirmed, the subsequent response had to be at least 4 weeks after the initial response. Two-sided 95% exact confidence interval (CI) was computed using the Clopper-Pearson method.

Time frame: From the date of randomization until date of confirmed CR or PR (maximum up to 25 months)

Population: ITT analysis set included all randomized participants. Participants were included in the treatment group assigned at randomization regardless of any actual treatment received.

DOR was defined as the time from the date of the first confirmed objective response (CR or PR that was subsequently confirmed) to the date of the first documented PD per RECIST v1.1 or death from any cause, whichever occurred first. CR was defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR was defined as at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Time frame: From the date of first documented response of CR or PR to the first documented PD or death from any cause, whichever occurred first (maximum up to 25 months)

Population: ITT analysis set included all randomized participants. Participants were included in the treatment group assigned at randomization regardless of any actual treatment received. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure. Only participants who achieved a confirmed CR or PR based on investigator assessment were included in the analysis.

The EORTC QLQ-CX24 questionnaire is meant for use among cervical cancer participants varying in disease stage and treatment modality. The EORTC-QLQ-CX24 questionnaire is composed of 24 questions for which the answers ranged from 1 (Not at all) to 4 (Very much). Four functional scales and 5 symptom scales will be calculated using the EORTC QLQ-CX24 Scoring Manual. The 9 scores computed from the EORTC-QLQ-CX24 questionnaire will be summarized by treatment arm using descriptive statistics.

Time frame: From start of treatment until end of follow-up

EQ5D is a participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state) ; higher scores indicate a better health state.

Time frame: From start of treatment until end of follow-up

The EORTC-QLQ-C30 questionnaire is composed of 30 questions for which the answers ranges either from 1 (not at all) to 4 (very much) for items 1 to 28, or from 1 (very poor) to 7 (excellent) for items 29 to 30. The EORTC QLQ-C30 scale scores will be calculated using the EORTC QLQ-C30 Scoring Manual. These include 5 functional scales, 3 symptom scales, a global health status/QoL scale, and 6 single items. Each of the multi-item scales includes a different set of items (i.e., no item occurs in more than one scale). All of the scales and single-item measures range in score from 0 to 100, with a high scale score representing a higher response level (e.g., a high level of functioning, a high QoL, or a high level of symptomatology/problems)

Time frame: From start of treatment until end of follow-up

The EQ-5D-5L questionnaire is a 5-item self-reported measure of functioning and well-being, which assesses 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension comprises 5 levels (no problems, slight problems, moderate problems, severe problems and extreme problems). Responses to the 5 items are then converted to a weighted health state index (utility score) based on values derived from general population samples. This health utility score is between 0 and 1, where 0 is death and 1 is perfect health.

Time frame: From start of treatment until end of follow-up

An AE was any untoward medical occurrence in a clinical study participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment and with onset date on or before 30 days after the last dose of study treatment.

Time frame: From start of treatment up to 30 days after last dose of study treatment (up to 25 months)

Population: Safety analysis set included all randomized participants who received at least 1 dose of study treatment (tisotumab vedotin or chemotherapy).

PFS per investigator was defined as the time from the date of randomization to the first documentation of disease progression (PD) as assessed by investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1, or death due to any cause, whichever occurred earlier. PD: at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). Participants without evidence of radiographic disease progression or death were censored at the date of last adequate tumor assessment prior to data cut-off date or start of new anti-cancer therapy. Participants with disease progression or death that occurred after 2 or more missed scans were censored at the last adequate tumor assessment prior to missed scans. Participants without post-baseline scan data were censored at the day of randomization.

Time frame: From the date of randomization to first documentation of PD or death due to any cause, or censoring date whichever occurred first (maximum up to 25 months)

Population: ITT analysis set included all randomized participants. Participants were included in the treatment group assigned at randomization regardless of any actual treatment received.

TTR was defined as the time from the randomization date to the date of the first confirmed objective response (CR or PR that was subsequently confirmed). CR was defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR was defined as at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Time frame: From the date of randomization to date of date of the first confirmed objective response (maximum up to 25 months)

Population: ITT analysis set included all randomized participants. Participants were included in the treatment group assigned at randomization regardless of any actual treatment received. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure. Only participants who achieved a confirmed CR or PR based on investigator assessment were included in the analysis.