J Clin Invest: MEK inhibitor cobimetinib combined with PD-L1 inhibitor atezolizumab prolongs PFS in biliary tract cancer (BTC)

MEK inhibitors have limited activity in biliary tract cancer (BTC) as monotherapy, but appear to enhance activity against programmed death ligand 1 (PD-L1) pathway inhibition

MEK inhibitors have limited activity in biliary tract cancer (BTC) as monotherapy, but appear to enhance activity against programmed death ligand 1 (PD-L1) pathway inhibition

This open-label phase II study (NCT03201458) randomized patients with BTC to atezolizumab (anti-PD-L1) monotherapy or in combination with cobimetinib (MEK inhibitor)

This open-label phase II study (NCT03201458) randomized patients with BTC to atezolizumab (anti-PD-L1) monotherapy or in combination with cobimetinib (MEK inhibitor)

From February 2018 to October 2018, 77 patients were enrolled with atezolizumab (n = 39) or atezolizumab + cobimetinib (n = 38)

The trial met its primary endpoint, with a median PFS of 3.

PFS

The ORRs of the combination and single-agent groups were 3.

The ORRs of the combination and single-agent groups were 3.

 Efficacy assessment

TRAEs of any grade occurred similarly in the two groups, with 33 (84.

TRAEs of any grade occurred similarly in the two groups, with 33 (84.

AEs

Taken together, the study showed that atezolizumab + cobimetinib combination therapy prolonged PFS compared with atezolizumab monotherapy, but the low response rates in both groups also indicated the immune- tolerant properties of BTC

Taken together, the study showed that atezolizumab + cobimetinib combination therapy prolonged PFS compared with atezolizumab monotherapy, but the low response rates in both groups also indicated the immune- tolerant properties of BTC

Original Source: Original Source:

Yarchoan M, Cope L, Ruggieri AN, Anders RA, Noonan AM, Goff LW, Goyal L, Lacy J, Li D, Patel AK, He AR, Abou-Alfa GK, Spencer K, Kim EJ, Davis SL, McRee AJ, Kunk PR, Goyal S, Liu Y, Dennison L, Xavier S, Mohan AA, Zhu Q, Wang-Gillam A, Poklepovic A, Chen HX, Sharon E, Lesinski GB, Azad NS.

Yarchoan M, Cope L, Ruggieri AN, Anders RA, Noonan AM, Goff LW, Goyal L, Lacy J, Li D, Patel AK, He AR, Abou-Alfa GK, Spencer K, Kim EJ, Davis SL, McRee AJ, Kunk PR, Goyal S, Liu Y, Dennison L, Xavier S, Mohan AA, Zhu Q, Wang-Gillam A, Poklepovic A, Chen HX, Sharon E, Lesinski GB, Azad NS.
Multicenter randomized phase II trial of atezolizumab with or without cobimetinib in biliary tract cancers.
J Clin Invest.
2021 Dec 15;131(24):e152670.
doi: 10.
1172/JCI152670.
PMID: 34907910; PMCID: PMC8670844.


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