Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Trifluridine/tipiracil · 8 trials · 7 indications
Overall survival defined as the observed time elapsed between the date of randomization and the date of death due to any cause. The primary estimand of interest was defined to assess the effect of the randomized treatments on the survival duration in all participants regardless of whether or not intercurrent events had occurred (treatment policy strategy). Analysis was performed using Kaplan- Meier method.
Overall survival defined as the observed time elapsed between the date of randomization and the date of death due to any cause. The primary estimand of interest was defined to assess the effect of the randomized treatments on the survival duration in all participants regardless of whether or not intercurrent events had occurred (treatment policy strategy). Analysis was performed using Kaplan- Meier method. In this outcome measure, data of survival probability at 6 months was reported.
Overall survival defined as the observed time elapsed between the date of randomization and the date of death due to any cause. The primary estimand of interest was defined to assess the effect of the randomized treatments on the survival duration in all participants regardless of whether or not intercurrent events had occurred (treatment policy strategy). Analysis was performed using Kaplan- Meier method. In this outcome measure, data of survival probability at 12 months was reported.
Overall survival defined as the observed time elapsed between the date of randomization and the date of death due to any cause. The primary estimand of interest was defined to assess the effect of the randomized treatments on the survival duration in all participants regardless of whether or not intercurrent events had occurred (treatment policy strategy). Analysis was performed using Kaplan- Meier method. In this outcome measure, data of survival probability at 18 months was reported.
Time elapsed between the randomization and the date of radiological tumour progression (according to RECIST 1.1) or death from any cause.
The occurrence of 3-4 neutropenia in mCRC patients undergoing treatment with the combination of bevacizumab and bi-weekly administration of trifluridine/tipiracil (experimental arm) compared to a conventional administration (control arm).
The progression-free survival (PFS) is the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse.
Response rate CR/PR
The progression free survival (PFS), defined as the time from the date of randomisation until the date of the investigator-assessed radiological disease progression or death due to any cause according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progressive disease (PD) was defined at least a 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) and an absolute increase of at least 5 mm in the sum of lesions or the appearance of new lesions.
Adverse event reporting will be graded following the National Cancer Institute of Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03
Vital sign measurements will include temperature, systolic and diastolic blood pressure, heart rate, and respiratory rate.
| Arm | Type | Description |
|---|---|---|
| Trifluridine/Tipiracil + Bevacizumab | EXPERIMENTAL | Participants were administered 35 milligrams per square meter per dose (mg/m²/dose) trifluridine/tipiracil (FTD/TPI) orally twice a day (BID), within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 an Day 13 to 14), over 2 weeks, followed by a 14-day rest; with bevacizumab (5 milligrams per kilogram \[mg/kg\], intravenous \[IV\] infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks. |
| Trifluridine/Tipiracil | ACTIVE_COMPARATOR | Participants were administered 35 mg/m²/dose of FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest. This treatment cycle was repeated every 4 weeks. |
| S95005 + Bevacizumab | EXPERIMENTAL | - |
| Capecitabine + Bevacizumab | ACTIVE_COMPARATOR | - |
| S95005 | EXPERIMENTAL | Film-coated tablet containing 15 mg of trifluridine and 7.065 mg of tipiracil hydrochloride, or 20 mg of trifluridine and 9.42 mg of tipiracil hydrochloride, taken orally twice a day at the dose of 35 mg/m²/dose. The treatment is given until progression of disease, unacceptable toxicity, investigator decision, patient refusal or until market authorization or reimbursement has been granted by the relevant Authority of the country where that patient is treated or until trifluridine / tipiracil is available by a doctor's prescription or can be accessed from another source or Sponsor decision. |
| Arm A (experimental) - Trifluridine/tipiracil plus bevacizumab biweekly administration | EXPERIMENTAL | Trifluridine/tipiracil: 35 mg/m², twice daily (BId) orally, on days 1-5 and days 15-19; 1 cycle every 28 days. \+ Bevacizumab: 5 mg/kg intravenously (IV) on day 1 and day 15; 1 cycle every 28 days. |
| Arm B (control) - Trifluridine/tipiracil plus bevacizumab conventional administration | ACTIVE_COMPARATOR | Trifluridine/tipiracil: 35 mg/m² Bid orally on days 1-5 and days 8-12; 1 cycle every 28 days. \+ Bevacizumab: 5 mg/kg IV on day 1 and day 15; 1 cycle every 28 days. |
| Trifluridine/Tipiracil + Oxaliplatin ± nivolumab | EXPERIMENTAL | Trifluridine/Tipiracil will be administered with a 14-day schedule (35 mg/m² twice-daily \[BID\] for 5 days followed by 9 days of recovery) until disease progression or intolerable toxicity. Oxaliplatin will be administered intravenously on day 1 of each treatment cycle (infusion duration: 2 hours), every 2 weeks. The first cycle will be administered at level -1 (70 mg/m²) and then increased to 85 mg/m² (if feasible) from the cycle 2 to 8 or until disease progression, whatever occurs first. In case of limiting-oxaliplatin neuropathy and in all cases after 8 cycles, oxaliplatin will be stopped and Trifluridine/Tipiracil will be continued alone until disease progression or intolerable toxicity. ± nivolumab 240 mg (infusion duration 30 minutes, every 2 weeks) until disease progression or intolerable toxicity for a maximum of 2 years. |
| FOLFOX ± nivolumab | ACTIVE_COMPARATOR | Folinic Acid 400 mg/m² (or 200 mg/m² if L-folinic acid) + oxaliplatin 85 mg/m² (infusion duration: 2 hours) followed by 5-FU bolus 400 mg/m² and then 5-FU 2400 mg/m² as a 46-hour continuous infusion. Treatment repeated every 14 days. In case of limiting-oxaliplatin neuropathy and in all cases after 8 cycles, oxaliplatin will be stopped and 5-FU (simplified LV5FU2 regimen) or capecitabine (1000 mg/m² BID during 2 weeks every 3 weeks) will be continued alone until disease progression or intolerable toxicity. ± nivolumab 240 mg (infusion duration 30 minutes, every 2 weeks) until disease progression or intolerable toxicity for a maximum of 2 years. |
| Treatment | EXPERIMENTAL | Treatment with TAS102 |
| S 95005 + oxaliplatin (+/- bevacizumab or nivolumab) | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Trifluridine/Tipiracil | DRUG | Taken by mouth two times a day, 5 days on/2 days off, over 2 weeks, followed by a 14-day rest |
| Bevacizumab | DRUG | administered every 2 weeks (Day 1 and Day 15) |
| Trifluridine/tipiracil hydrochloride (S95005) | DRUG | Film-coated tablets of S 95005 (35 mg/m²/dose) will be administered orally twice a day (BID), within 1 hour after completion of morning and evening meals, 5 days on/2 days off, over 2 weeks, followed by a 14-day rest; This treatment cycle will be repeated every 4 weeks. |
| Capecitabine | DRUG | Film-coated tablets, Capecitabine (1250 mg/m²/dose) will be administered orally BID on Days 1-14 of each cycle. This treatment cycle will be repeated every 3 weeks. |
| Bevacizumab experimental | BIOLOGICAL | Concentrate for solution for infusion, Bevacizumab (5 mg/kg, IV) administered every 2 weeks (Day 1 and Day 15). This treatment cycle will be repeated every 4 weeks. |
| Bevacizumab control | BIOLOGICAL | Concentrate for solution for infusion, Bevacizumab (7.5 mg/kg, IV) will be administered on Day 1 of each cycle.This treatment cycle will be repeated every 3 weeks. |
| Oxaliplatin | DRUG | Oxaliplatin will be administered intravenously on day 1 of each treatment cycle (infusion duration: 2 hours), every 2 weeks. The first cycle will be administered at level -1 (70 mg/m²) and then increased to 85 mg/m² (if feasible) from the cycle 2 to 8 or until disease progression, whatever occurs first. In case of limiting-oxaliplatin neuropathy and in all cases after 8 cycles, oxaliplatin will be stopped and Trifluridine/Tipiracil will be continued alone until disease progression or intolerable toxicity. |
| FOLFOX regimen | DRUG | Folinic Acid 400 mg/m² (or 200 mg/m² if L-folinic acid) + oxaliplatin 85 mg/m² (infusion duration: 2 hours) followed by 5-FU bolus 400 mg/m² and then 5-FU 2400 mg/m² as a 46-hour continuous infusion. Treatment repeated every 14 days. In case of limiting-oxaliplatin neuropathy and in all cases after 8 cycles, oxaliplatin will be stopped and 5-FU (simplified LV5FU2 regimen) or capecitabine (1000 mg/m² BID during 2 weeks every 3 weeks) will be continued alone until disease progression or intolerable toxicity. |
| Nivolumab | DRUG | Nivolumab 240 mg (infusion duration 30 minutes, every 2 weeks) until disease progression or intolerable toxicity for a maximum of 2 years |
| Trifluridine/tipiracil + bevacizumab | DRUG | Patients were treated withTrifluridine/tipiracil + bevacizumab regimen until they met a discontinuation criterion. |
| Capecitabine + bevacizumab | DRUG | Patients were treated with capecitabine+ bevacizumab regimen until they met a discontinuation criterion. |
| Trifluridine/tipiracil hydrochloride (S 95005) | DRUG | Film-coated tablets containing 15mg of trifluridine and 7.065mg of tipiracil hydrochloride, or 20mg of trifluridine and 9.42mg of tipiracil hydrochloride, given orally at the dose of 25 or 30 or 35 mg/m2/dose, until unacceptable toxicity according to the investigator, disease progression or patient withdrawal. |
Inclusion Criteria: 1. Has histologically confirmed unresectable adenocarcinoma of the colon or rectum (all other histological types are excluded). 2. RAS status must have been previously determined (mutant or wild-type) based on local assessment of tumor biopsy. 3. Has received a maximum of 2 prio...
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