Favourable Phase Ib Results For Pembrolizumab In Malignant Pleural Mesothelioma

KEYNOTE-028 findings add to evidence for a role for pembrolizumab in the treatment of malignant pleural mesothelioma

medwireNews: Select patients with malignant pleural mesothelioma could derive benefit from treatment with the programmed death 1 (PD-1) inhibitor pembrolizumab, preliminary KEYNOTE-028 results suggest.

“Pembrolizumab appears to be well tolerated and might confer anti-tumour activity in patients with PD-L1 [programmed cell death ligand 1]-positive malignant pleural mesothelioma”, the investigators report in The Lancet Oncology.

The phase Ib study included 25 patients with locally advanced or metastatic pleural mesothelioma with PD-L1 expression in at least 1% of tumour cells. The patients had all previously received chemotherapy and had an ECOG performance status of 0 or 1.

Pembrolizumab 10 mg/kg was given every 2 weeks for 2 years or until confirmed progression or unacceptable toxicity; treatment lasted for a median of 5.1 months, although at data cut off 48% of the patients had used the drug for at least 6 months and median follow-up was 18.7 months.

The majority (64%) of patients experienced at least one treatment-related adverse event, with grade 1 nausea the most common side effect reported by five patients, followed by fatigue and dry mouth in three patients each.

Grade 2 fatigue and arthralgia were each reported by three patients and pruritus by two, while there were single cases of grade 3 decreased appetite, dyspnoea, pyrexia, alanine aminotransferase elevation, iridocyclitis, decreased neutrophil count and thrombocytopenia.

One patient required a dose reduction following grade 2 elevation in γ-glutamyltransferase and a grade 3 elevation in alanine aminotransferase, while immune-related adverse events resulted in dose interruption in three patients, all of whom later returned to treatment.

Using RECIST criteria, there were no complete responses to pembrolizumab therapy but 20% of patients had a partial response and 52% of patients achieved stable disease, lasting a median of 5.6 months.

Overall, 40% of patients derived a clinical benefit, defined as a complete or partial response or stable disease for at least 6 months, say Evan Alley, from the University of Pennsylvania in Philadelphia, USA, and co-authors.

Median duration of response to treatment was 12.0 months. “Three of the reported responses were ongoing and one patient continued to derive clinical benefit at the time of data cutoff, suggesting durability of response”, the researchers comment.

Median progression-free survival was 5.4 months, with 45.8% and 20.8% of patients remaining free from progression at 6 and 12 months, respectively. Median overall survival was 18.0 months with corresponding 6- and 12-month rates of 83.5% and 62.6%.

“The results from this phase 1b KEYNOTE-028 trial, showing clinical benefit in a proportion of patients with PD-L1-positive malignant pleural mesothelioma, indicate that further assessment of pembrolizumab in this patient group is warranted”, the researchers summarise.

Several phase II trials of pembrolizumab in malignant pleural mesothelioma are now underway, including the KEYNOTE-158 basket trial assessing biomarkers of pembrolizumab response, the KEYNOTE-139 study of fixed-dose pembrolizumab as second-line therapy and an active-comparator trial comparing first-line combinations of pembrolizumab, cisplatin and pemetrexed .


Alley EW, Lopez J, Santoro A, et al. Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial. Lancet Oncol; Advance online publication 10 March 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30169-9

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