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Lenvatinib plus pembrolizumab effective for thyroid cancer subset

MUNICH — The combination of lenvatinib and pembrolizumab appeared effective for a small cohort of patients with metastatic anaplastic or poorly differentiated thyroid carcinoma, according to study results presented at European Society for Medical Oncology Congress.

The combination — which also appeared safe — now will be systematically examined in the phase 2 ATLEP clinical trial, according to Christine Dierks, PhD student and researcher in the department of hematology/oncology at University Medical Center Freiburg in Germany, and colleagues.

The majority of patients with metastatic anaplastic or poorly differentiated thyroid carcinoma have a poor prognosis. They typically only survive a few months despite extensive multimodal treatment. The tumors are highly proliferative and are characterized by numerous somatic mutations, according to study background.

The analysis included eight patients (anaplastic, n = 6; poorly differentiated, n = 2), all of whom had more than 100 somatic mutations as determined by whole-exome sequencing, as well as PD-L1 expression greater than 1%.

Patients received antiangiogenic therapy with lenvatinib (Lenvima, Eisai) dosed at 24 mg/kg once daily and reduced to 14 mg/kg upon development of intolerable side effects, such as uncontrollable high blood pressure, weight loss or loss of appetite. Three to 8 weeks later, patients received the immune checkpoint inhibitor pembrolizumab (Keytruda, Merck) at a fixed dose of 200 mg every 3 weeks.

Treatment durations with the combination ranged from 1 month to 27 months.

Researchers observed no continuous grade 3 or grade 4 toxicities with the combination. Three patients experienced weight loss and three patients developed high blood pressure, but both toxicities were normalized after reductions in lenvatinib dose.

One patient died due to progression of a cervical tumor 5 days after receiving the first pembrolizumab dose. All other patients achieved at least stable disease. Four patients achieved partial response and one patient achieved complete remission.

Six patients remained on therapy at the time of analysis, with treatment durations ranging from 3 months to 27 months.

“The majority of patients are still on therapy, implicating this treatment combination as a safe and effective treatment regimen for this extremely bad prognostic patient cohort,” Dierks and colleagues wrote. – by Jennifer Southall

 

Reference:

Dierks C, et al. Abstract 1824P. Presented at: European Society for Medical Oncology Congress; Oct. 19-23, 2018; Munich.

 

Disclosures: Dierks reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.

MUNICH — The combination of lenvatinib and pembrolizumab appeared effective for a small cohort of patients with metastatic anaplastic or poorly differentiated thyroid carcinoma, according to study results presented at European Society for Medical Oncology Congress.

The combination — which also appeared safe — now will be systematically examined in the phase 2 ATLEP clinical trial, according to Christine Dierks, PhD student and researcher in the department of hematology/oncology at University Medical Center Freiburg in Germany, and colleagues.

The majority of patients with metastatic anaplastic or poorly differentiated thyroid carcinoma have a poor prognosis. They typically only survive a few months despite extensive multimodal treatment. The tumors are highly proliferative and are characterized by numerous somatic mutations, according to study background.

The analysis included eight patients (anaplastic, n = 6; poorly differentiated, n = 2), all of whom had more than 100 somatic mutations as determined by whole-exome sequencing, as well as PD-L1 expression greater than 1%.

Patients received antiangiogenic therapy with lenvatinib (Lenvima, Eisai) dosed at 24 mg/kg once daily and reduced to 14 mg/kg upon development of intolerable side effects, such as uncontrollable high blood pressure, weight loss or loss of appetite. Three to 8 weeks later, patients received the immune checkpoint inhibitor pembrolizumab (Keytruda, Merck) at a fixed dose of 200 mg every 3 weeks.

Treatment durations with the combination ranged from 1 month to 27 months.

Researchers observed no continuous grade 3 or grade 4 toxicities with the combination. Three patients experienced weight loss and three patients developed high blood pressure, but both toxicities were normalized after reductions in lenvatinib dose.

One patient died due to progression of a cervical tumor 5 days after receiving the first pembrolizumab dose. All other patients achieved at least stable disease. Four patients achieved partial response and one patient achieved complete remission.

Six patients remained on therapy at the time of analysis, with treatment durations ranging from 3 months to 27 months.

“The majority of patients are still on therapy, implicating this treatment combination as a safe and effective treatment regimen for this extremely bad prognostic patient cohort,” Dierks and colleagues wrote. – by Jennifer Southall

 

Reference:

Dierks C, et al. Abstract 1824P. Presented at: European Society for Medical Oncology Congress; Oct. 19-23, 2018; Munich.

 

Disclosures: Dierks reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.

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