LBA20 - FOLFOXIRI plus bevacizumab (bev) plus atezolizumab (atezo) versus FOLFOXIRI plus bev as first-line treatment of unresectable metastatic colorectal cancer (mCRC) patients: Results of the phase II randomized AtezoTRIBE study by GONO

Background

FOLFOXIRI/bev is an upfront therapeutic option for selected mCRC pts. Immune checkpoint inhibitors (ICIs) reported remarkable achievements in dMMR but not in pMMR mCRC. The association of cytotoxics and bev may promote the sensitivity to ICIs increasing the exposure of neoantigens, inducing immunogenic cell death, and increasing the immune infiltration in tumor microenvironment while reducing the activity of Tregs.

Methods

AtezoTRIBE was a prospective, open label, phase II, comparative trial in which initially unresectable mCRC patients, irrespective of MMR status, were randomized 1:2 to receive up to 8 cycles of FOLFOXIRI/bev (arm A) or FOLFOXIRI/bev/atezo (arm B), followed by maintenance with 5-FU/bev or 5FU/bev/atezo until disease progression. The primary endpoint was PFS. Assuming a median PFS of 12 months in arm A, 201 patients and 129 events were required to detect a HR of 0.66 in favour of arm B with 1-sided α and β errors of 0.10 and 0.15. Trial info: NCT03721653.

Results

From November 2018 to February 2020, 218 pts were enrolled (arm A/B: 73/145) in 22 Italian sites. Main pts’ characteristics were (arm A/B): right-sided 44%/44%, synchronous metastases 89%/86%, liver-only 22%/22%, RAS mutant 71%/73%, BRAF mutant 14%/8%, dMMR 7%/6%. At a median follow up of 19.9 mos, 159 (arm A/B: 60/99) PFS events were collected. A significant advantage by the addition of atezo was observed in PFS (13.1 vs 11.5 mos, HR 0.69, 80%CI 0.56-0.85, p=0.012), but not in ORR (59% vs 64%, p=0.412). No safety issues were evident. Significant interaction effect between MMR status and treatment arm was found (p=0.010). In the pMMR subgroup (N=199, arm A/B: 67/132), 147 (arm A/B: 54/93) PFS events were collected. Significantly longer PFS was reported in arm B (12.9 vs 11.4 mos, HR 0.78, 80%CI 0.62-0.97, p=0.071).

Conclusions

The primary endpoint was met: the addition of atezo to FOLFOXIRI/bev prolongs PFS of mCRC patients. While the magnitude of benefit is significantly higher in dMMR tumors, signals of efficacy are reported also in the pMMR subgroup. Translational analyses to identify predictive biomarkers are ongoing.

Clinical trial identification

NCT03721653.

Editorial acknowledgement

Legal entity responsible for the study

G.O.N.O. Group.

Funding

G.O.N.O. Group.

Disclosure

C. Cremolini: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Servier; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Expert Testimony: Amgen; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: Bayer; Financial Interests, Institutional, Invited Speaker: Servier; Financial Interests, Institutional, Invited Speaker: Merck. D. Rossini: Financial Interests, Personal, Invited Speaker: Takeda. F. Pietrantonio: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: Serono; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Servier; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Institutional, Funding: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Merck Serono; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Servier; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Funding: AstraZeneca. S. Lonardi: Financial Interests, Personal, Speaker’s Bureau: Amgen; Financial Interests, Personal, Speaker’s Bureau: Merck; Financial Interests, Personal, Speaker’s Bureau: Serono; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly & co; Financial Interests, Personal, Speaker’s Bureau: Merck Serono; Financial Interests, Institutional, Funding: Amgen; Financial Interests, Institutional, Funding: Merck Serono. A. Falcone: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: Merck Serono; Financial Interests, Personal, Invited Speaker: Celgene; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Funding: Amgen; Financial Interests, Institutional, Funding: Merck Serono. All other authors have declared no conflicts of interest.