One year after the FDA approval of 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), results of the LEAP-005 study showed that several other advanced solid tumors, including biliary tract cancer, may also respond to this combination. The results of the LEAP-005 study were presented at the 2020 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. Zarnie Lwin, MBBS, Senior Staff Specialist, Medical Oncology, Cancer Care Services, Department of Medical Oncology, University of Queensland, Herston, Australia, and colleagues studied 187 patients aged ≥18 years with 1 of 6 advanced solid tumors. 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, or biliary tract cancer (excluding ampulla of Vater).
The study participants received lenvatinib 20 mg daily plus pembrolizumab 200 mg every 3 weeks. Treatment was continued for 35 weeks or until confirmed disease progression or unacceptable toxicity. 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 for the CRC cohort with 32 patients), with the intention to expand the number of patients up to 100 for cohorts in which sufficient efficacy was observed. The primary end points were objective response rate (ORR) by blinded central review per Response Evaluation Criteria in Solid Tumors version 1.1 and safety.
At the data cut-off of April 10, 2020, the median follow-up was 8.6 months (range, 1.9-13.1 months). The efficacy was encouraging across all tumor types, with ORRs ranging 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.
The 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. The median duration of response was 3.2 months in glioblastoma multiforme, 5.3 months in biliary tract cancer, and, at the time of cut-off, had not been reached in the other cohorts. 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%) and the least common in patients with glioblastoma multiforme (35%). Grade ≥3 adverse events in the other tumor types 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%); gastric cancer, glioblastoma multiforme, and biliary tract cancer each had a 6% discontinuation rate.
This study is ongoing and, given the promising activity observed across the 6 tumor types, all the cohorts are being expanded to include up to 100 patients for each cohort.
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