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Clinical Trial
. 2015 Oct 6;6(30):30394-407.
doi: 10.18632/oncotarget.4724.

Critical role of bevacizumab scheduling in combination with pre-surgical chemo-radiotherapy in MRI-defined high-risk locally advanced rectal cancer: Results of the BRANCH trial

Antonio Avallone  1 , Biagio Pecori  2 , Franco Bianco  3 , Luigi Aloj  4 , Fabiana Tatangelo  5 , Carmela Romano  1 , Vincenza Granata  6 , Pietro Marone  7 , Alessandra Leone  8 , Gerardo Botti  5 , Antonella Petrillo  6 , Corradina Caracò  4 , Vincenzo R Iaffaioli  1 , Paolo Muto  2 , Giovanni Romano  3 , Pasquale Comella  1 , Alfredo Budillon  8 , Paolo Delrio  9
Affiliations
Clinical Trial

Critical role of bevacizumab scheduling in combination with pre-surgical chemo-radiotherapy in MRI-defined high-risk locally advanced rectal cancer: Results of the BRANCH trial

Antonio Avallone et al. Oncotarget. .

Abstract

Background: We have previously shown that an intensified preoperative regimen including oxaliplatin plus raltitrexed and 5-fluorouracil/folinic acid (OXATOM/FUFA) during preoperative pelvic radiotherapy produced promising results in locally advanced rectal cancer (LARC). Preclinical evidence suggests that the scheduling of bevacizumab may be crucial to optimize its combination with chemo-radiotherapy.

Patients and methods: This non-randomized, non-comparative, phase II study was conducted in MRI-defined high-risk LARC. Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 2 weeks before the start of chemo-radiotherapy, and on the same day of chemotherapy for 3 cycles (concomitant-schedule A) or 4 days prior to the first and second cycle of chemotherapy (sequential-schedule B). Primary end point was pathological complete tumor regression (TRG1) rate.

Results: The accrual for the concomitant-schedule was early terminated because the number of TRG1 (2 out of 16 patients) was statistically inconsistent with the hypothesis of activity (30%) to be tested. Conversely, the endpoint was reached with the sequential-schedule and the final TRG1 rate among 46 enrolled patients was 50% (95% CI 35%-65%). Neutropenia was the most common grade ≥ 3 toxicity with both schedules, but it was less pronounced with the sequential than concomitant-schedule (30% vs. 44%). Postoperative complications occurred in 8/15 (53%) and 13/46 (28%) patients in schedule A and B, respectively. At 5 year follow-up the probability of PFS and OS was 80% (95%CI, 66%-89%) and 85% (95%CI, 69%-93%), respectively, for the sequential-schedule.

Conclusions: These results highlights the relevance of bevacizumab scheduling to optimize its combination with preoperative chemo-radiotherapy in the management of LARC.

Keywords: adjuvant chemotherapy; bevacizumab; locally advanced rectal cancer; preoperative chemo-radiotherapy; vessel normalization.

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Conflict of interest statement

CONFLICTS OF INTEREST

Antonio Avallone: honoraria from Roche for participation in conferences as speaker and in advisory board meetings. All other authors have declared no conflict interest.

Figures

Figure 1
Figure 1. Kaplan-Meier survival curves
Dashed curves represent 95% CIs. A. Progression-free survival for the schedule B. B. Overall survival for the schedule B.
Figure 2
Figure 2. Treatment schedules
See this image and copyright information in PMC

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