BACCI: A phase II randomized, double-blind, multicenter, placebo-controlled study of capecitabine (C) bevacizumab (B) plus atezolizumab (A) or placebo (P) in refractory metastatic colorectal cancer (mCRC): An ACCRU network study

Mettu, Niharika B.; Twohy, Erin; Ou, Fang Shu; Halfdanarson, Thorvardur R.; Lenz, Heinz‐Josef; Breakstone, Rimini; Boland, Patrick M.; Crysler, Oxana; Wu, Christina; Grothey, Axel; Nixon, Andrew B.; Bolch, Emily; Niedzwiecki, Donna; Fruth, Briant; Schweitzer, Brock L.; Elsing, A.; Hurwitz, H.; Fakih, Marwan; Bekaii‐Saab, Tanios

doi:10.1093/annonc/mdz246.011

Cited by 63 publications

(55 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, the critical challenge is to develop novel strategy to remodel the immunosuppressive microenvironment in order to target pMMR/MSS mCRC. Although the combination of PD-1 blockade with VEGF (vascular endothelial growth factor) inhibition has been investigated in some clinical trials, randomized studies in mCRC failed to show significant improvement in PFS or OS with this combination (17,18). The antiangiogenic multikinase inhibitor regorafenib has recently been shown to exhibit immunomodulatory activity when combined with ICI in mice model of mCRC, probably via targeting both the VEGF pathway and other immune-modulating molecules such as CSF1R (colony-stimulating factor 1 receptor) (19).…”

Section: Discussionmentioning

confidence: 99%

The Efficacy and Safety of Regorafenib in Combination With Anti-PD-1 Antibody in Refractory Microsatellite Stable Metastatic Colorectal Cancer: A Retrospective Study

Liu

Liu³

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

The Efficacy and Safety of Regorafenib in Combination With Anti-PD-1 Antibody in Refractory Microsatellite Stable Metastatic Colorectal Cancer: A Retrospective Study

Liu

Liu³

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

“…These preliminary Phase I data prompted the initiation of a number of randomized studies evaluating the combination of PD-(L)1 antibodies and anti-VEGF drugs in mCRC. The BACCI study, a placebo-controlled randomized Phase II study, evaluated the addition of atezolizumab to bevacizumab and capecitabine in refractory mCRC (108). Approximately, 86% of randomized patients had MSS mCRC.…”

Section: Mss Colorectal Cancermentioning

confidence: 99%

“…In patients with MSS tumors, the PFS benefit was more pronounced (HR 0.67). Response rate and OS were not significantly increased (108). Maintenance therapy with atezolizumab following induction treatment with FOLFOX plus bevacizumab in first-line mCRC was evaluated in the MODUL study (142).…”

Section: Mss Colorectal Cancermentioning

confidence: 99%

Augmenting Anticancer Immunity Through Combined Targeting of Angiogenic and PD-1/PD-L1 Pathways: Challenges and Opportunities

Hack¹,

Zhu

Wang³

2020

Front. Immunol.

172

132

View full text Add to dashboard Cite

show abstract

“…Consistently, unsatisfactory results were reported with the addition of atezolizumab to the oral fluoropyrimidine capecitabine and bevacizumab in the chemorefractory setting, providing a statistically significant modest improvement in PFS in the BACCI trial (4.4 vs. 3.3 months, HR = 0.72; p = 0.051) [23].…”

Section: Anti-vegf and Chemotherapy + Immune Checkpoint Inhibitorsmentioning

confidence: 65%

Immune Checkpoint Inhibitors in pMMR Metastatic Colorectal Cancer: A Tough Challenge

Marmorino

Boccaccino

Germani

et al. 2020

Cancers

View full text Add to dashboard Cite

The introduction of checkpoint inhibitors provided remarkable achievements in several solid tumors but only 5% of metastatic colorectal cancer (mCRC) patients, i.e., those with bearing microsatellite instable (MSI-high)/deficient DNA mismatch repair (dMMR) tumors, benefit from this approach. The favorable effect of immunotherapy in these patients has been postulated to be due to an increase in neoantigens due to their higher somatic mutational load, also associated with an abundant infiltration of immune cells in tumor microenvironment (TME). While in patients with dMMR tumors checkpoint inhibitors allow achieving durable response with dramatic survival improvement, current results in patients with microsatellite stable (MSS or MSI-low)/proficient DNA mismatch repair (pMMR) tumors are disappointing. These tumors show low mutational load and absence of “immune-competent” TME, and are intrinsically resistant to immune checkpoint inhibitors. Modifying the interplay among cancer cells, TME and host immune system is the aim of multiple lines of research in order to enhance the immunogenicity of pMMR mCRC, and exploit immunotherapy also in this field. Here, we focus on the rationale behind ongoing clinical trials aiming at extending the efficacy of immunotherapy beyond the MSI-high/dMMR subgroup with particular regard to academic no-profit studies.

show abstract

BACCI: A phase II randomized, double-blind, multicenter, placebo-controlled study of capecitabine (C) bevacizumab (B) plus atezolizumab (A) or placebo (P) in refractory metastatic colorectal cancer (mCRC): An ACCRU network study

Cited by 63 publications

References 0 publications

The Efficacy and Safety of Regorafenib in Combination With Anti-PD-1 Antibody in Refractory Microsatellite Stable Metastatic Colorectal Cancer: A Retrospective Study

The Efficacy and Safety of Regorafenib in Combination With Anti-PD-1 Antibody in Refractory Microsatellite Stable Metastatic Colorectal Cancer: A Retrospective Study

Augmenting Anticancer Immunity Through Combined Targeting of Angiogenic and PD-1/PD-L1 Pathways: Challenges and Opportunities

Immune Checkpoint Inhibitors in pMMR Metastatic Colorectal Cancer: A Tough Challenge

Contact Info

Product

Resources

About