The following article features coverage from the European Society for Medical Oncology (ESMO) 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Despite a nearly 4-fold initial response rate advantage over chemotherapy, patients receiving pembrolizumab immunotherapy for malignant pleural mesothelioma (MPM) did not experience longer overall survival (OS) or progression-free duration, according to findings from the randomized, multicenter, open-label phase 3 PROMISE-meso trial (ClinicalTrials.gov Identifier: NCT02991482). The study was presented at the European Society of Medical Oncology (ESMO) Congress 2019 in Spain.1 

“[U]nfortunately, these responses did not delay progression or improve survival,”

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said lead study author Sanjay Popat, MD, of the Royal Marsden Hospital NHS Foundation Trust in London, England, in a press release.2 “These findings are disappointing but, as in previous studies, some patients benefited from immunotherapy for long periods. If we can find out how this happens, we will have a better idea of which patients should preferentially receive this treatment over chemotherapy.” 

While pembrolizumab was not superior to chemotherapy, survival times were similar, suggesting immunotherapy might offer an alternative to chemotherapy, Dr Popat suggested.

The study was the first randomized trial to evaluate the efficacy of pembrolizumab vs single-agent chemotherapy in MPM patients who progressed after or on previous platinum-based chemotherapy, Dr Popat noted. 

Between September 2017 and August 2018, 144 patients were enrolled and randomly assigned in a 1:1 ratio to receive either pembrolizumab (73 individuals) or chemotherapy (71 individuals). At a February 20, 2019, data lock, at a median follow-up of 12 months, OS was 10.7 months vs 11.7 months for pembrolizumab and chemotherapy, respectively (hazard ratio [HR], 1.05; 95% CI, 0.66-1.67; P =.85, not significant). Median progression-free duration was 2.5 months vs 3.4 months (HR, 1.06; 95% CI, 0.73-1.53; P =.76, not significant).

Grade 3 to grade 5 treatment-related adverse events affected 19% and 24% of patients in the pembrolizumab and chemotherapy study groups, respectively, including 1 patient death in each group. The most common adverse event in the pembrolizumab group was fatigue (19%), and nausea and fatigue (27% and 31%) were the most common side effects for chemotherapy. 

“In studies of lung cancer, we have already learned that we can improve results with immunotherapy by combining it with chemotherapy and the same may be true with mesothelioma,” Dr Popat said. “I would advise clinicians to enroll their patients into one of the large ongoing trials of first-line combination treatment so we can get answers as soon as possible about how to improve mesothelioma treatment.”

Disclosure: This study was funded by MSD Merck Sharp & Dohme AG. For a full list of disclosures, please refer to the abstract.

Read more of Cancer Therapy Advisor‘s coverage of the ESMO annual meeting by visiting the conference page.

References

  1. Popat S, Curioni-Fontecedro A, Polydoropoulou V, et al. A multicenter randomized phase III trial comparing pembrolizumab versus standard chemotherapy for advanced pre-treated malignant pleural mesothelioma (MPM) – results from the European Thoracic Oncology Platform (ETOP 9-15) PROMISE-meso trial. Presented at: European Society of Medical Oncology (ESMO) Congress 2019; September 27-October 1, 2019: Barcelona, Spain. Abstract LBA91_PR.
  2. European Society of Medical Oncology (ESMO). Mesothelioma trial suggests immunotherapy as an alternative to chemotherapy [press release]. Published September 20, 2019.