The two-drug combination of Keytruda (pembrolizumab) plus Lenvima (lenvatinib) was associated with prolonged benefit and safety in patients with malignant pleural mesothelioma, according to findings from the phase 2 PEMMELA clinical trial presented at the 2022 World Conference on Lung Cancer.
Preliminary results indicated the objective response rate — which is the percentage of patients whose disease shrunk — was 58%. According to the investigators, 76% of patients required dose reductions.
“This study met its primary end point, showing promising clinical activity of (Keytruda) plus (Lenvima) in patients with recurrent (malignant pleural mesothelioma) who progressed after chemotherapy, with remarkable but no unexpected toxicity,” said Li-Anne Douma, a doctoral candidate at The Netherlands Cancer Institute in Amsterdam who presented the results.
In patients with malignant pleural mesothelioma, there is a large unmet need for effective second-line treatment options. The PD-1 blocker, Keytruda, has shown a response rate up to 20% as monotherapy, whereas Lenvima, a multi-targeted tyrosine kinase inhibitor has synergistic interactions with PD-1 blocking in other tumors.
Because of this, investigators sought to evaluate the clinical activity and toxicity of the two agents in combination as treatment for patients with recurrent malignant pleural mesothelioma in the phase 2 single-arm, open-label, study.
The trial included 38 eligible patients with malignant pleural mesothelioma whose disease progressed after chemotherapy. They received intravenous Keytruda given at a dose of 200 milligrams (mg) once every three weeks plus Lenvima at 20 mg orally once a day.
Enrollment was open to patients aged 18 years or older with malignant pleural mesothelioma. Patients had an ECOG performance status of 0-1 (indicating that their disease had little to no effect on performing daily activities); measurable disease according to the modified RECIST version 1.1, a system of measuring mesothelioma; and had received prior chemotherapy. Those enrolled remained on treatment for up to two years, until unacceptable toxicity, or disease progression evaluated by CT-scan every six weeks.
Objective response rate was defined as the proportion of patients with complete response (complete disappearance of disease), or partial response (shrinking of disease), with secondary end points including safety of the treatment combination, disease control rate at months three and six and progression-free survival (time from treatment until disease gets worse).
At a data cutoff of March 31, 2022, 22 of the 38 patients had reached partial response as best overall response, and 15 of these patients had confirmed partial response of 39.5%. Among the seven patients who had unconfirmed partial response, three can still reach confirmed partial response.
In regard to safety, most of the side effects were deemed mild or moderate and consisted of fatigue (21 patients), hoarseness (21 patients), anorexia (13 patients), diarrhea (13 patients), high blood pressure (five patients) and elevated alanine aminotransferase/ aspartate transaminase levels, which could be an indicator of liver damage (five patients).
Serious or severe treatment-related side effects were observed in 26 patients with the most common serious side effects being high blood pressure in eight patients (24%) and anorexia in three (18%). Additionally, there were two patients with severe myositis (inflamed muscles) as well as 10 patients with 13 treatment-related serious side effects.
Dose reductions or permanent discontinuation of Lenvima treatment were required by 76% of all patients due to toxicity concerns. For Keytruda, two of the 38 patients (8%) had permanent discontinuation on the trial.
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