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AMEBICA

Modified FOLFIRINOX Versus CISGEM Chemotherapy for Patients With Advanced Biliary Tract Cancer (PRODIGE 38 AMEBICA): A Randomized Phase II Study

Phase 2/3N = 191NCT02591030

Population
Patients with locally advanced or metastatic biliary tract cancer and ECOG performance status 0 or 1
Design
Open-label randomised (1:1) phase 2/3 study in 43 French centres of modified FOLFIRINOX (oxaliplatin, irinotecan and infusional fluorouracil) versus cisplatin and gemcitabine (CISGEM) for a maximum of 6 months. The paper reports the phase 2 part: the primary end point was the 6-month progression-free survival rate in the modified intention-to-treat population (patients who received at least one dose), assessed by RECIST version 1.1, with statistical assumptions of a 6-month rate of at least 59% (73% expected). 191 patients were randomly assigned.
Primary endpoint
6-month progression-free survival rate
Arms
  • Modified FOLFIRINOX (experimental): Oxaliplatin, irinotecan and infusional fluorouracil (modified FOLFIRINOX) for a maximum of 6 months
  • Cisplatin and gemcitabine (CISGEM) (control): Cisplatin and gemcitabine (CISGEM) for a maximum of 6 months
People
Phelip JM
Δ 6-month progression-free survival rate−2.7 pointsΔ median OS−2.1 monthsΔ median PFS−1.2 months
Show the numbers
Results reported for AMEBICA
EndpointAnalysisModified FOLFIRINOXCisplatin and gemcitabine (CISGEM)Effect
6-month progression-free survival rateModified intention-to-treat population (patients who received at least one dose): 185 patients, 92 modified FOLFIRINOX and 93 CISGEMprimaryPhelip 202244.6%47.3%The confidence intervals in the abstract are 90% intervals: 35.7 to 53.7 for modified FOLFIRINOX and 38.4 to 56.3 for CISGEM. The abstract states that modified FOLFIRINOX did not meet the primary end point.
OSModified intention-to-treat population (patients who received at least one dose): 185 patientsprimarymedian follow-up 21 monthsPhelip 2022median 11.7 months (9.5–14.2)median 13.8 months (10.9–16.1)Phase 2 part; the abstract names the 6-month progression-free survival rate as the primary end point and gives no hazard ratio or P value for overall survival.
PFSModified intention-to-treat population (patients who received at least one dose): 185 patientsprimarymedian follow-up 21 monthsPhelip 2022median 6.2 months (5.5–7.8)median 7.4 months (5.6–8.7)Phase 2 part; the abstract gives no hazard ratio or P value.
Results reported for AMEBICA
EndpointAnalysisModified FOLFIRINOXCisplatin and gemcitabine (CISGEM)Effect
6-month progression-free survival rateModified intention-to-treat population (patients who received at least one dose): 185 patients, 92 modified FOLFIRINOX and 93 CISGEMprimaryPhelip 202244.6%47.3%The confidence intervals in the abstract are 90% intervals: 35.7 to 53.7 for modified FOLFIRINOX and 38.4 to 56.3 for CISGEM. The abstract states that modified FOLFIRINOX did not meet the primary end point.
OSModified intention-to-treat population (patients who received at least one dose): 185 patientsprimarymedian follow-up 21 monthsPhelip 2022median 11.7 months (9.5–14.2)median 13.8 months (10.9–16.1)Phase 2 part; the abstract names the 6-month progression-free survival rate as the primary end point and gives no hazard ratio or P value for overall survival.
PFSModified intention-to-treat population (patients who received at least one dose): 185 patientsprimarymedian follow-up 21 monthsPhelip 2022median 6.2 months (5.5–7.8)median 7.4 months (5.6–8.7)Phase 2 part; the abstract gives no hazard ratio or P value.
Illustrative — modelled from reported values, not trial data. OS, primary.
0%25%50%75%100%051015202530Months (modelled)
  • Modified FOLFIRINOX (experimental)
  • Cisplatin and gemcitabine (CISGEM) (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsModified FOLFIRINOXCisplatin and gemcitabine (CISGEM)
0100.0%100.0%
958.7%63.6%
1736.5%42.6%
2621.4%27.1%
3512.6%17.2%
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%051015Months (modelled)
  • Modified FOLFIRINOX (experimental)
  • Cisplatin and gemcitabine (CISGEM) (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsModified FOLFIRINOXCisplatin and gemcitabine (CISGEM)
0100.0%100.0%
557.2%62.6%
936.6%43.0%
1420.9%26.9%
1912.0%16.9%
Primary publication: Phelip JM, Desrame J, Edeline J, Barbier E, Terrebonne E, Michel P, et al. Modified FOLFIRINOX Versus CISGEM Chemotherapy for Patients With Advanced Biliary Tract Cancer (PRODIGE 38 AMEBICA): A Randomized Phase II Study. J Clin Oncol. 2022;40(3):262-271. PubMedDOI

Appears in

Sources

  1. Phelip JM, Desrame J, Edeline J, Barbier E, Terrebonne E, Michel P, et al. Modified FOLFIRINOX Versus CISGEM Chemotherapy for Patients With Advanced Biliary Tract Cancer (PRODIGE 38 AMEBICA): A Randomized Phase II Study. J Clin Oncol. 2022;40(3):262-271.

    PubMedDOI