Treatments after progression to first-line FOLFOXIRI and bevacizumab in metastatic colorectal cancer: a pooled analysis of TRIBE and TRIBE2 studies by GONO

Daniele Rossini, Sara Lonardi, Carlotta Antoniotti, Daniele Santini, Gianluca Tomasello, Paola Ermacora, Marco Maria Germani, Francesca Bergamo, Vincenzo Ricci, Salvatore Caponnetto, Roberto Moretto, Alberto Zaniboni, Filippo Pietrantonio, Angela Buonadonna, Giuliana Ritorto, Gianluca Masi, Tiziana Pia Latiano, Stefania Rapisardi, Alfredo Falcone, Chiara Cremolini, Daniele Rossini, Sara Lonardi, Carlotta Antoniotti, Daniele Santini, Gianluca Tomasello, Paola Ermacora, Marco Maria Germani, Francesca Bergamo, Vincenzo Ricci, Salvatore Caponnetto, Roberto Moretto, Alberto Zaniboni, Filippo Pietrantonio, Angela Buonadonna, Giuliana Ritorto, Gianluca Masi, Tiziana Pia Latiano, Stefania Rapisardi, Alfredo Falcone, Chiara Cremolini

Abstract

Background: FOLFOXIRI/bevacizumab (bev) is a first-line regimen of proven activity and efficacy in metastatic colorectal cancer. The upfront exposure to three cytotoxics raises concerns about the efficacy of treatments after progression.

Methods: We performed a pooled analysis of treatments after progression to upfront FOLFOXIRI/bev in patients enrolled in two randomised Phase 3 studies (TRIBE and TRIBE2) that compared FOLFOXIRI/bev to doublets (FOLFOX or FOLFIRI)/bev. Response rate, progression-free survival (2nd PFS) and overall survival (2nd OS) during treatments after progression were assessed. The RECIST response in first line and the oxaliplatin and irinotecan-free interval (OIFI) were investigated as potential predictors of benefit from FOLFOXIRI ± bev reintroduction.

Results: Longer 2nd PFS was reported in patients receiving FOLFOXIRI ± bev reintroduction compared to doublets ± bev or other treatments (6.1 versus 4.4 and 3.9 months, respectively, P = 0.013), and seems limited to patients achieving a response during first line (6.9 versus 4.2 and 4.7 months, respectively, P = 0.005) and an OIFI ≥ 4 months (7.2 versus 6.5 and 4.6 months, respectively, P = 0.045).

Conclusions: First-line FOLFOXIRI/bev does not impair the administration of effective second-line therapies. First-line response and longer OIFI seem associated with improved response and 2nd PFS from FOLFOXIRI ± bev reintroduction, without impacting 2nd OS.

Conflict of interest statement

C.A., D.S., G.T., P.E., M.M.G., F.B., V.R., S.C., R.M., A.B., G.R., G.M., T.P.L. and S.R. declare no competing interests. D.R.: travel, accommodations and expenses—Takeda. S.L.: consulting or advisory role—Amgen, Lilly, Merck Serono and SERVIER. Speakers’ Bureau—Bristol-Myers Squibb, Lilly, Merck Serono, Roche and Servier. Research funding— Amgen and Merck Serono. A.Z.: consulting or advisory role—Amgen, Bayer, Merck Serono and Servier. Speakers’ Bureau—Servier. F.P.: consulting or advisory role—Amgen, Bayer, Lilly, Merck Serono, Roche, Sanofi and SERVIER. Research funding—Bristol-Myers Squibb. A.F.: honoraria—Amgen, Lilly, Merck, Roche and SERVIER. Consulting or advisory role—Amgen, Bayer, Bristol-Myers Squibb, Lilly, Merck, Roche and SERVIER. Research funding—Amgen (Inst), Bayer (Inst), Merck (Inst), MSD (Inst), Roche (Inst), Sanofi (Inst) and SERVIER (Inst). Travel, accommodations and expenses—Amgen, Bayer, Merck, Roche and SERVIER. C.C.: honoraria—Amgen, Bayer, Roche and SERVIER. Consulting or advisory role—Amgen, Bayer and Roche. Speakers’ Bureau—SERVIER. Research funding—Merck. Travel, accommodations and expenses—Roche and SERVIER.

Figures

Fig. 1. TRIBE and TRIBE2 pooled-analysis flowchart.
Fig. 1. TRIBE and TRIBE2 pooled-analysis flowchart.
EGFR: Epidermal Growth Factor Receptor.
Fig. 2. 2nd PFS (a) and 2nd…
Fig. 2. 2nd PFS (a) and 2nd OS (b) according to treatment received after progression to first-line FOLFOXIRI/Bev.
Bev bevacizumab, CI confidence interval.
Fig. 3. 2nd PFS in patients achieving…
Fig. 3. 2nd PFS in patients achieving (a) or not (b) an objective response to first-line FOLFOXIRI/Bev according to treatment received after progression.
Bev bevacizumab, CI confidence interval.
Fig. 4. 2nd PFS in patients achieving…
Fig. 4. 2nd PFS in patients achieving an OIFI ≥ 4 months (a) or
Bev bevacizumab, CI confidence interval.

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