Immunotherapy Findings Positive For Relapsed Malignant Pleural Mesothelioma

Second- or third-line nivolumab monotherapy and nivolumab plus ipilimumab may extend survival for patients with relapsed malignant pleural mesothelioma

medwireNews: Updated MAPS2 trial findings reported at the ESMO 2017 Congress support the role of single-agent or combination immunotherapy in patients with relapsed malignant pleural mesothelioma (MPM).

Adding bevacizumab to first-line pemetrexedcisplatin chemotherapy has been demonstrated to improve overall survival (OS) for patients with MPM but no second-line treatment has previously been shown effective, said presenting author Gérard Zalcman, from Hôpital Bichat-Claude Bernard and Université Paris-Diderot in France.

He reported data for the MAPS2 study showing that patients given nivolumab alone and those given nivolumab plus ipilimumab achieved the primary endpoint of a meaningful increase in the 12-week disease control rate, compared with data from patients in a historical series or non-immunotherapy agent trials.

In all, 63 patients were randomly assigned to receive the programmed cell death protein 1 (PD-1) inhibitor nivolumab 3 mg/kg every 2 weeks, while 61 patients were given nivolumab at the same dose plus the anti-cytotoxic T-lymphocyte associated protein 4 (CTLA4) agent ipilimumab 1 mg/kg every 6 weeks. Both patient groups were treated for 2 years or until disease progression or unacceptable toxicity.

Gérard Zalcman told delegates at the meeting that patient accrual was estimated to take 18 months but was completed in less than 5 months, and at data cutoff in July 2017, disease progression had occurred in 85.2% of nivolumab-treated patients versus 63.6% of those given nivolumab plus ipilimumab.

Toxicity was described as “globally manageable”. Drug-related adverse events occurred in 88.9% of the nivolumab arm and 93.4% of the combined treatment arm, with grade 3 events reported in 12.7% versus 22.9%, and grade 4 events in 0.0% versus 3.3%. There were no drug-related deaths with nivolumab alone, but three in the nivolumab plus ipilimumab group, attributed to fulminant hepatitis, encephalitis and acute kidney failure.

Patient-reported outcome measures indicated a trend towards better quality of life at 12 weeks with nivolumab in terms of global, pain, anorexia and interference items but general and symptom distress scores favoured the combination treatment. However, Gérard Zalcman noted that long-term and longitudinal quality of life study findings are pending.

At 12 weeks, the primary endpoint of disease control rate was 44.4% with nivolumab versus 50.0% with combination therapy for the first 108 eligible patients, with corresponding rates of 39.7% versus 51.6% for the full intention-to-treat population of 125 patients.

Analysis of patients by programmed cell death ligand 1 (PD-L1) expression using a cutoff of 1% or above suggested that positive patients were significantly more likely to respond to treatment than negative patients. When a cutoff of 25% or above was used, both objective response and disease control rates were significantly higher in PD-L1-positive than -negative patients.

Median duration of response was 7.4 months with nivolumab and 7.9 months with nivolumab plus ipilimumab.

Progression-free survival after a median of 15.0 months was 4.0 months with nivolumab versus 5.6 months with the combined therapy. OS data are yet to mature but at 15 months, OS was a median of 13.6 months with nivolumab and unreached in patients given nivolumab plus ipilimumab.

“MAPS2 updated results support the recent National Comprehensive Cancer Network panel decision to recommend the monotherapy or combination therapy as options for second/third line therapy in relapsing MPM patients”, Gérard Zalcman concluded.


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