PRODIGE 9: trial | Bending the Curve: Trial by Trial

PRODIGE 9

Multicenter Phase III Randomized Study of FOLFIRI Plus Bevacizumab Following or Not by a Maintenance Therapy With Bevacizumab in Patients With Non-Pretreated Metastatic Colorectal Cancer

Phase 3N = 491NCT00952029

Population

Previously untreated metastatic colorectal cancer

Design

Open-label randomised phase 3 trial comparing tumour control duration with bevacizumab maintenance versus no treatment (observation) during chemotherapy-free intervals after induction with 12 cycles of fluorouracil, leucovorin and irinotecan (FOLFIRI) plus bevacizumab; after progression the induction regimen was repeated for eight cycles, followed by a new chemotherapy-free interval. 491 patients were randomly assigned between March 2010 and July 2013; progression or death occurred during induction chemotherapy in 85 (17%).

Arms

Observation (control): No treatment during chemotherapy-free intervals
Bevacizumab maintenance (experimental): Bevacizumab maintenance during chemotherapy-free intervals

People

Aparicio T

Δ median Tumour control duration0 monthsΔ median PFS+0.3 monthsΔ median OS−0.3 monthsΔ median Tumour control duration−5.5 months

Show the numbers

Results reported for PRODIGE 9
Endpoint	Analysis	Bevacizumab maintenance	Observation	Effect
Tumour control durationAll randomised patients (analysis population not stated in the abstract)	primaryAparicio 2018	median 15 months	median 15 months	Median tumour control duration was 15 months in both groups, higher than the trial's hypotheses according to the abstract. No hazard ratio or interval is given in the abstract.
PFSAll randomised patients (analysis population not stated in the abstract)	primaryAparicio 2018	median 9.2 months	median 8.9 months	Progression-free survival from randomisation; no hazard ratio or interval is given in the abstract.
OSAll randomised patients (analysis population not stated in the abstract)	primaryAparicio 2018	median 21.7 months	median 22 months	No hazard ratio or interval is given in the abstract.
Tumour control durationPer-protocol population (at least one reinduction after the first progression)	exploratoryAparicio 2018	median 17.8 months	median 23.3 months	P=0.339Median duration of the first chemotherapy-free interval was 4.3 months in both arms; per-protocol progression-free survival 9.9 and 9.5 months and overall survival 27.6 and 28.5 months (maintenance and observation).

Results reported for PRODIGE 9
Endpoint	Analysis	Bevacizumab maintenance	Observation	Effect
Tumour control durationAll randomised patients (analysis population not stated in the abstract)	primaryAparicio 2018	median 15 months	median 15 months	Median tumour control duration was 15 months in both groups, higher than the trial's hypotheses according to the abstract. No hazard ratio or interval is given in the abstract.
PFSAll randomised patients (analysis population not stated in the abstract)	primaryAparicio 2018	median 9.2 months	median 8.9 months	Progression-free survival from randomisation; no hazard ratio or interval is given in the abstract.
OSAll randomised patients (analysis population not stated in the abstract)	primaryAparicio 2018	median 21.7 months	median 22 months	No hazard ratio or interval is given in the abstract.
Tumour control durationPer-protocol population (at least one reinduction after the first progression)	exploratoryAparicio 2018	median 17.8 months	median 23.3 months	P=0.339Median duration of the first chemotherapy-free interval was 4.3 months in both arms; per-protocol progression-free survival 9.9 and 9.5 months and overall survival 27.6 and 28.5 months (maintenance and observation).

Illustrative — modelled from reported values, not trial data. Tumour control duration, primary.

Show curves

Bevacizumab maintenance (experimental)
Observation (control)

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

Data table (modelled values)

Months	Bevacizumab maintenance	Observation
0	100.0%	100.0%
9	66.0%	66.0%
19	41.6%	41.6%
28	27.4%	27.4%
38	17.3%	17.3%

Illustrative — modelled from reported values, not trial data. PFS, primary.

Show curves

Bevacizumab maintenance (experimental)
Observation (control)

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

Data table (modelled values)

Months	Bevacizumab maintenance	Observation
0	100.0%	100.0%
6	63.6%	62.7%
12	40.5%	39.3%
17	27.8%	26.6%
23	17.7%	16.7%

Appears in

2006 Stop-and-go and maintenance therapy: OPTIMOX1 to PRODIGE 9

Sources

Aparicio T, Ghiringhelli F, Boige V, Le Malicot K, Taieb J, Bouché O, et al. Bevacizumab Maintenance Versus No Maintenance During Chemotherapy-Free Intervals in Metastatic Colorectal Cancer: A Randomized Phase III Trial (PRODIGE 9). J Clin Oncol. 2018;36(7):674-681.
PubMed DOI