medwireNews: Preliminary results suggest a role for the combination of the CTLA-4 inhibitor tremelimumab and the PD-L1 blocker durvalumab in the treatment of inoperable pleural or peritoneal mesothelioma.
Among the 40 participants of the phase II NIBIT-MESO-1 trial receiving first- or second-line therapy, induction with tremelimumab 1 mg/kg plus durvalumab 20 mg/kg every 4 weeks for four cycles followed by nine cycles of maintenance durvalumab led to an immune-related RECIST objective response rate of 28%. All responses were partial responses, and lasted for a median of 16.1 months.
In 10 (25%) patients, the responses were confirmed by computed tomography at the 6-week mark or later, which was the threshold set by the authors to indicate active treatment.
The immune-related disease control rate was 65%, while the median immune-related progression-free survival was 8 months, with 55% of participants free from progression at 6 months, and 28% at 12 months.
Median overall survival was 16.6 months and the 1-year survival rate was 62%, report Michele Maio (University Hospital of Siena, Italy) and team.
Of note, they found no association between baseline tumoral PD-L1 positivity, defined by any cutoff ranging from 0% to 50%, and any of these outcome measures, but the authors caution that “the study was not powered to detect differences of less than 40% for these thresholds.”
Reporting on the safety, Maio et al note that the combination had “a good safety profile,” with 18% of patients experiencing treatment-related adverse events of grade 3 or 4, of which three led to treatment discontinuation.
They summarize in The Lancet Respiratory Medicine that “[t]he combined use of monoclonal antibodies targeting CTLA4 and PD-1 or PD-L1 might significantly affect the clinical course of patients with malignant mesothelioma.”
And the team concludes: “Further studies are needed to explore this combination in more homogeneous populations of patients with mesothelioma, as well as exploratory studies to investigate the activity of tremelimumab and durvalumab in combination with emerging modulators of the tumour microenvironment.”
Paul Baas and Maria Disselhorst, both from The Netherlands Cancer Institute in Amsterdam, say in an accompanying commentary that “[t]he availability of new checkpoint inhibitors and the interest of pharmaceutical companies in testing drugs for malignant pleural mesothelioma means that the future of these patients looks brighter than ever before.”
They hope the current findings “will help to further establish priorities for research on malignant mesothelioma.”
The commentators continue: “In particular, researchers should focus on biomarkers other than PD-L1, and patient characteristics and biomarkers will need to be studied prospectively to identify subgroups of patients that will benefit from immuno-oncology therapy.”
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