Bevacizumab Maintenance Versus No Maintenance During Chemotherapy-Free Intervals in Metastatic Colorectal Cancer: A Randomized Phase III Trial (PRODIGE 9)

Abstract

Purpose Conflicting results are reported for maintenance treatment with bevacizumab during chemotherapy-free intervals (CFI) in metastatic colorectal cancer after induction chemotherapy. Patients and Methods In this open-label, phase III, randomized controlled trial, we compared the tumor control duration (TCD) observed with bevacizumab maintenance and with no treatment (observation) during CFI subsequent to induction chemotherapy with 12 cycles of fluorouracil, leucovorin, and irinotecan plus bevacizumab. After disease progression, the induction regimen was repeated for eight cycles, followed by a new CFI. Results From March 2010 to July 2013, 491 patients were randomly assigned. Disease progression or death occurred during induction chemotherapy in 85 patients (17%); 261 patients (53%) had at least one reinduction, 107 (22%) had two reinductions, and 56 (11%) had three or more reinductions. The median TCD was 15 months in both groups; the median progression-free survival (PFS) from randomization was 9.2 and 8.9 months in the maintenance group and observation groups, respectively. The TCD observed in both groups was higher compared with the TCD hypotheses of the trial. The median overall survival (OS) was 21.7 and 22.0 months in the maintenance and observation groups, respectively. In the per-protocol population, defined as patients with at least one reinduction after the first progression, the median duration of the first CFI was 4.3 months in both arms; the median TCD was 17.8 and 23.3 months ( P = .339), the median PFS was 9.9 and 9.5 months, and the median OS was 27.6 and 28.5 months in the maintenance and observation groups, respectively. Multivariable analysis revealed that female gender, WHO performance status ≥ 2, and unresected primary tumors were associated with a shorter TCD. Conclusion Bevacizumab maintenance monotherapy did not improve TCD, CFI duration, PFS, or OS.

A Retrospective Exploration of Targeted Maintenance Therapy in Advanced Colorectal Cancer: Based on the Background of Chinese Patient Assistance Program

“…The prognosis of patients with CRC is poor (2,3); that is, more than half of patients will ultimately develop metastases (4)(5)(6). The median overall survival (OS) in patients with mCRC is ∼30 months (7) due to the availability of several chemotherapy drugs and targeted drugs as well as the development and popularization of multidisciplinary treatment models (8)(9)(10).…”

Do we make progress in elderly patients with metastatic colorectal cancer?

“…Whether the effect on PFS can be ascribed to the use of bevacizumab, capecitabine or the combination is not known. The use of bevacizumab alone as maintenance in the French PRODIGE 9 study did not reveal any superiority [57].…”

Panitumumab‐based maintenance after oxaliplatin discontinuation in metastatic colorectal cancer: A retrospective analysis of two randomised trials

“…28 Furthermore, the PRODIGE 9 Phase III trial of bevacizumab maintenance treatment found no benefit over observation alone, against a range of endpoints. 29 A meta-analysis of bevacizumab-based maintenance therapy reported improvements in time-tofailure-of-strategy and PFS, and a trend to improvements in OS, compared with complete stop. 30 As patients in this analysis of maintenance therapy are anti-EGFR-experienced and a selection bias may therefore exist, this should be borne in mind when considering the observed toxicity profilespatients who discontinued treatment due to unacceptable toxicity were not evaluated.…”