2859 - Treatments (tx) after progression to first-line FOLFOXIRI + bevacizumab (bev) in metastatic colorectal cancer (mCRC) patients (pts): A pooled analysis of TRIBE and TRIBE-2 studies by GONO.

Background

FOLFOXIRI + bev is regarded as a valuable option in the first-line tx of mCRC pts. A possible concern for the adoption is the feasibility and efficacy of tx after progression, and especially the reintroduction of the same agents used upfront. The aim of the study was to evaluate the efficacy of tx after progression among pts treated with first-line FOLFOXIRI + bev in the phase III TRIBE (NCT00719797) and TRIBE2 (NCT02339116) studies. The impact of the oxaliplatin and irinotecan free interval (OIFI), defined as the time from the last administration of oxaliplatin and irinotecan to disease progression, on the efficacy of tx after progression was also investigated.

Methods

Data about tx received after progression including 2^ndPFS (i.e. the time from 2^nd line tx start to disease progression or death) were collected. The efficacy of tx after progression according to the duration of the OIFI was explored. A cut-off value of 4 months was adopted.

Results

Out of 586 pts treated with upfront FOLFOXIRI + bev, 520 progressed. Among 409 (79%) pts who received a tx after progression, 168 (41%) received FOLFOXIRI ± bev (Group A) and 241 (59%) received other tx (Group B), including FOLFOX or FOLFIRI ± bev or other agents not used in first line in 124 and 117 cases, respectively. Anti-EGFR moAbs were administered in 68 cases.

Pts in Group A experienced significantly longer 2^nd PFS than pts in Group B (median 2^nd PFS: 6.1 vs 4.2, HR 0.76, 95%CI 0.62-0.94; p = 0.012). Pts with an OIFI ≥ 4 mos (n = 279) had longer 2^nd PFS than those with an OIFI < 4 mos (n = 130) independently of the second-line tx (6.1 vs 3.7 mos: HR 0.54, 95%CI 0.42-0.69; p < 0.001). In the subgroup of pts with an OIFI ≥ 4 mos FOLFOXIRI ± bev (n = 125) was associated with longer 2^nd PFS compared to other tx (n = 154) (7.2 vs 5.5 mos; HR 0.75, 95% CI 0.58-0.97; p = 0.029). Conversely, in pts with an OIFI < 4 mos no significant difference was shown between Group A (n = 43) and B (n = 87) (4.4 vs 3.2; HR 0.94, 95%CI 0.65-1.36; p = 0.75).

Conclusions

Tx after progression to first-line FOLFOXIRI + bev were feasible. Pts with longer OIFI showed better 2^nd PFS and seemed to derive more benefit from the reintroduction of the triplet.

Clinical trial identification

TRIBE NCT00719797 TRIBE2 NCT02339116.

Editorial acknowledgement

Legal entity responsible for the study

G.O.N.O.: Gruppo Oncologico Nord Ovest.

Funding

Has not received any funding.

Disclosure

S. Lonardi: Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Merck Serono; Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Speaker Bureau / Expert testimony: Servier. D. Santini: Advisory / Consultancy: Amgen; Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche; Advisory / Consultancy: MSD; Advisory / Consultancy: Eisai; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Janssen; Advisory / Consultancy: Merck. A. Falcone: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (institution), Advisory / Consultancy: Lilly; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Servier. C. Cremolini: Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy: Amgen; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Servier. All other authors have declared no conflicts of interest.