Mesothelioma patients whose disease progressed after receiving a first-line treatment of nivolumab plus ipilimumab achieved a 60 percent objective response rate when treated with second-line pembrolizumab plus lenvatinib therapy. Dutch researchers report that twenty patients experienced a median progression-free survival of 6.9 months and disease control rates of 90 percent at 3 months and 52.6 percent at 6 months.
Mesothelioma Treatment Success Countered by Substantial Toxicity
In a study reported in The Lancet Oncology, mesothelioma researchers from the Netherlands Cancer Institute in Amsterdam reported that patients whose original, first-line treatment with the FDA-approved combination of nivolumab plus ipilimumab had failed were treated with pembrolizumab at 200 mg every 3 weeks plus lenvatinib at 20 mg daily for up to 2 years or until disease progression or unacceptable toxicity.
The single-center phase II PEMMELA study is specifically studying whether a protocol that has shown synergistic activity in preclinical and clinical studies in treating solid tumors will provide positive results for patients diagnosed with mesothelioma. The protocol features pembrolizumab, an anti-PD-1 antibody, and lenvatinib, an antiangiogenic multikinase inhibitor.
Researchers Encouraged by Response In Mesothelioma Patients
The scientists report that one mesothelioma patient experienced a complete response while 11 others showed a partial response to the treatment, which was administered between December 2022 and March 2023. There were 20 study participants in all, and at the median follow-up time of 11.9 months, the researchers found a median response of 8.6 months. Unfortunately, grade 3 or 4 treatment-related adverse events occurred in 85 percent of patients, with the most common side effects including hypertension, fatigue, and musculoskeletal pain, all of which were scored at grade 3 severity. Grade 4 events consisted of hyponatremia, decreased neutrophils, and respiratory failure in one patient each, with treatment-related serious adverse events observed in 35 percent of patients.
The tolerability challenges that came with the treatment resulted in 45 percent of the mesothelioma patients requiring at least one dose reduction of one of the two medications, with two patients (10%) discontinuing treatment due to toxicity. No treatment-related deaths occurred during the study period. Lead investigator Dr. Jacobus A. Burgers of the Department of Thoracic Oncology at the Netherlands Cancer Institute concluded that the study had met its primary endpoint, showing high clinical activity of the pembrolizumab plus lenvatinib combination after first-line nivolumab plus ipilimumab, though with substantial toxicity. He called the drug combination promising for future studies.
If you or someone you love has been diagnosed with mesothelioma, the Patient Advocates at Mesothelioma.net can help point you to helpful resources and support. For more information, contact them today at 1-800-692-8608.
