IBCSG 54-16

ETOP IBCSG Partners Foundation

Effingerstrasse 33, Bern, Switzerland, 3008

ETOP IBCSG Partners Foundation, ETOP IBCSG Partners Foundation, +41 31 511 94 00, ibcsg-regulatory@etop.ibcsg.org

ETOP IBCSG Partners Foundation, ETOP IBCSG Partners Foundation, +41 31 511 94 00, ibcsg-regulatory@etop.ibcsg.org

No

No

No

Final

04 Dec 2021

Yes

17 Nov 2021

Yes

23 Nov 2022

Yes

To assess efficacy, as measured by the time to treatment failure (TTF), of the first-line combination treatment with vinorelbine, cyclophosphamide and capecitabine (VEX) in comparison with paclitaxel monotherapy in ER+/HER2–, metastatic or locally advanced breast cancer patients, who have progressed under previous endocrine therapy.

Participating institutions’ ethics committees or Institutional Review Boards approved the trial according to local laws and regulations. All patients gave written informed consent, and the trial was performed in compliance with the Helsinki Declaration. The Data Safety and Monitoring Board reviewed the data from this research throughout the study.

13 Sep 2017

No

Yes

Italy: 140

140

140

0

0

0

0

0

0

91

49

0

Overall Study (overall period)

Randomised - controlled

Yes

Paclitaxel

Concentrate for solution for infusion

Intravenous use

Paclitaxel 90 mg/m2 i.v. days 1, 8, 15 every 4 weeks, according to standard local practice

Cyclophosphamide

Endoxan Baxter

Coated tablet

Oral use

Cyclophosphamide 50 mg orally once daily around 9am

Capecitabine

Film-coated tablet

Oral use

Capecitabine 500 mg, orally 3 times a day (total 1500 mg/day) within 30 minutes after meals (breakfast, lunch, dinner)

Vinorelbine

Capsule

Oral use

Vinorelbine 40 mg orally days 1, 3, 5 each week (Monday, Wednesday, Friday) after lunch

Paclitaxel

Metronomic VEX

Analysis Population Paclitaxel

• Efficacy analysis population: All randomized patients who receive at least one dose of trial treatment. • Safety population: All randomized patients who receive at least one dose of trial treatment will be included in assessments of safety and tolerability. (thus the two populations are the same)

Analysis Population VEX

• Efficacy analysis population: All randomized patients who receive at least one dose of trial treatment. • Safety population: All randomized patients who receive at least one dose of trial treatment will be included in assessments of safety and tolerability. (thus the two populations are the same)

Paclitaxel

Metronomic VEX

Analysis Population Paclitaxel

• Efficacy analysis population: All randomized patients who receive at least one dose of trial treatment. • Safety population: All randomized patients who receive at least one dose of trial treatment will be included in assessments of safety and tolerability. (thus the two populations are the same)

Analysis Population VEX

• Efficacy analysis population: All randomized patients who receive at least one dose of trial treatment. • Safety population: All randomized patients who receive at least one dose of trial treatment will be included in assessments of safety and tolerability. (thus the two populations are the same)

Efficacy and tolerability, measured by time to treatment failure, of metronomic oral vinorelbine plus cyclophosphamide and capecitabine (VEX) versus weekly paclitaxel, using an intent-to-treat analysis approach.

Primary

Assessed at the start of every 4-week (28-day) treatment cycle from randomization to the end of treatment date or discontinuation; median follow-up was 29 months, with a minimum of 0.2 months and maximum of 48.5 months.

Analysis Population Paclitaxel v Analysis Population VEX

133

Pre-specified

0.61

2-sided

Defined as best overall response of complete response (CR) or partial response (PR), or stable disease (SD) (or non-CR/non-PD in the case of non-measurable disease only) lasting for at least 24 weeks (at least 2 scans), measured from randomization until first documentation of progressive disease. Best overall response was defined as best response recorded from randomization across all time points until disease progression. Confirmation of partial or complete response by an additional scan was not requested in this trial. Disease response and progression were assessed according to the revised Response Evaluation Criteria in Solid Tumors (RECIST version 1.1)

Secondary

Tumor measurements were assessed at baseline, and every 12 weeks (± 2 weeks) from randomization until first disease progression on the basis of clinical and radiological tumor assessments, on average approximately 9 months.

PFS was defined as time from randomization until documented disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria or death, whichever occurred first; the death must have occurred within an interval of time corresponding to the interval of tumor re-evaluations. For patients without progression, follow-up was censored at the date of last disease assessment.

Secondary

Tumor measurements were assessed at baseline, and every 12 weeks (± 2 weeks) from randomization until first disease progression on the basis of clinical and radiological tumor assessments, on average approximately 9 months.

Overall survival from time of randomisation will be summarised for each treatment group.

Secondary

From day 1 of cycle 1 until death from any cause (censored at date of last assessment of vital status for patients lost to follow up), assessed up to 36 months from the enrollment of the first patient.

Adverse Events (AEs) were collected from the first dose of trial medication, at day 1 of every treatment cycle, until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication.

AEs were collected from the first dose of trial medication until 28 days after all treatment discontinuation (EOT visit), regardless of whether it is considered related to a medication. The main criterion for tolerability is the occurrence of toxicities and adverse events.

4.0

Analysis Population Paclitaxel

Analysis Population VEX