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Benefits of Lenvatinib plus Pembrolizumab in Solid Tumors, Including Biliary Tract Cancer

2020 Year in Review: Cholangiocarcinoma — December 19, 2020

First results of the multicohort phase 2 LEAP-005 study suggest that lenvatinib plus pembrolizumab combination immunotherapy has promising antitumor activity in patients with biliary tract cancer.

One year after the FDA approved the combination of lenvatinib (Lenvima), a multikinase inhibitor, plus the immunotherapy pembrolizumab (Keytruda), a PD-1 inhibitor, for the treatment of patients with advanced endometrial cancer that is not microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR), the LEAP-005 study results showed that several other advanced solid tumors, including biliary tract cancer, may also respond to this combination. The LEAP-005 study results were presented at this year’s virtual meeting of the European Society for Medical Oncology (ESMO).

These first results of the phase 2 LEAP-005 study, an open-label, multicohort clinical trial of lenvatinib plus pembrolizumab, were presented as a late-breaking abstract at the ESMO meeting. A total of 187 patients aged ≥18 years with 1 of 6 advanced solid tumors were studied by Zarnie Lwin, MBBS, Senior Staff Specialist, Medical Oncology, Cancer Care Services, Department of Medical Oncology, University of Queensland, Herston, Australia, and colleagues. The 6 solid tumors were triple-negative breast cancer (TNBC), ovarian cancer, gastric cancer, colorectal cancer (CRC that is not MSI-H or dMMR), glioblastoma multiforme, and biliary tract cancer (excluding ampulla of Vater).

Study participants received lenvatinib 20 mg daily plus pembrolizumab 200 mg every 3 weeks. Treatment was continued for 35 weeks or until disease progression was confirmed or toxicity was unacceptable. The tumor cohorts received the combination therapy as second or third line for TNBC, fourth line for ovarian cancer, third line for gastric cancer, and third line for CRC (non–MSI-H/dMMR), second line for glioblastoma multiforme, and second line for biliary tract cancer.

Each cohort included 31 patients (except 32 patients for the CRC cohort). The intention was to expand the number of patients ≤100 for cohorts in which sufficient efficacy was observed. The primary end points were objective response rate (ORR) by safety and blinded central review per Response Evaluation Criteria in Solid Tumors version 1.1.


As of April 10, 2020, the data cutoff date, median follow-up was 8.6 months (range, 1.9-13.1 months). The efficacy was encouraging across all tumor types. The ORRs ranged from 10% to 32% in the following tumor types: 10% in gastric cancer (95% confidence interval [CI], 2-26) and biliary tract cancer (95% CI, 2-26); 16% (95% CI, 6-34) in glioblastoma multiforme; 22% (95% CI, 9-40) in CRC; 29% (95% CI, 14-48) in TNBC; and 32% (95% CI, 17-51) in ovarian cancer.

Disease control rates were 48% in gastric cancer, 68% in biliary tract cancer, 58% in glioblastoma multiforme, 47% in CRC, 58% in TNBC, and 74% in ovarian cancer. Median duration of response was 3.2 months in glioblastoma multiforme, 5.3 months in biliary tract cancer, and not reached in the other cohorts at the time of cutoff. The longest duration of response observed was 10.4+ months, which was seen in a patient with CRC.


The safety of lenvatinib plus pembrolizumab was deemed manageable. The most common grade ≥3 treatment-related adverse events were reported in patients with ovarian cancer (68%). The least common adverse events were reported in patients with glioblastoma multiforme (35%). In patients with other tumor types, grade ≥3 adverse events were 42% in gastric cancer, 48% in biliary tract cancer, 50% in CRC, and 55% in TNBC.

The proportion of patients discontinuing treatment because of adverse events was also highest in patients with ovarian cancer (13%), followed by TNBC (10%) and CRC (9%); discontinuation rate was 6% for patients with gastric cancer, glioblastoma multiforme, and biliary tract cancer.

This study is ongoing and, considering the promising activity observed across the 6 tumor types, all cohorts are being expanded to include ≤100 patients per cohort.

Source: Lwin Z, et al. Ann Oncol. 2020;38(4_suppl). Abstract LBA41.

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