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Potential treatment approach in malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM), a malignancy usually associated with long-term asbestos exposure, is notoriously difficult to treat and has a very poor prognosis. To date, no treatment is recommended in MPM patients progressing after 1st-line pemetrexed-platinum doublet; disease control rate (DCR) is <30% with all previously tested drugs in the second line setting. Preliminary results suggested possible activity of anti-PD-1 mAb in 2nd/3rd-line, opposed to single agent anti-CTLA-4 mAb.

In today´s oral abstract session on lung cancer – Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers, a randomized non comparative phase 2 trial was presented, which evaluated the efficacy of anti-PD1 mAb Nivolumab (Nivo)-monotherapy and anti-PD-1 + anti-CTLA-4 (Ipilimumab, Ipi)-combination therapy in MPM.

The trial included 125 patients with PS 0-1 and histologically proven MPM (measurable disease) relapsing after 1 or 2 prior lines including pemetrexed/platinum doublet. Patients received Nivo 3 mg/kg q2w or Nivo 3 mg/kg q2w + Ipi 1 mg/kg q6w until progression or unacceptable toxicity. After twelve weeks, DCR analysis assessed by blinded independent central review in the first 108 eligible patients documented unprecedented DCR-rates of 42.6% with Nivo and 51.9% with Nivo+Ipi. ORR was 16.7% with Nivo and 25.9% with Nivo+Ipi. All grade/G3-4 toxicities were slightly increased in the combination arm vs. Nivo alone.

The current data suggest that mono- and combination-immunotherapy may provide new treatment options and a significant clinical benefit in this difficult cohort.

References

Scherpereel A et al., abstract LBA8507: Second- or third-line nivolumab (Nivo) versus nivo plus ipilimumab (Ipi) in malignant pleural mesothelioma (MPM) patients: Results of the IFCT-1501 MAPS2 randomized phase II trial

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