Keytruda, the brand name for pembrolizumab, was the poster child for mesothelioma immunotherapy.
In the past couple of years, its momentum has stalled, stepping aside for similar immune checkpoint inhibitors like Opdivo (nivolumab) and Yervoy (ipilimumab). Opdivo and Yervoy for mesothelioma is FDA-approved, as of October 2020.
A recent clinical trial may not change much, but there are some promising footnotes regarding mesothelioma cases.
The KEYNOTE-158 study released data from the phase 2 investigation, which had 118 malignant pleural mesothelioma patients receive at least one dose of Keytruda. The data shows a benefit for specific types of mesothelioma cases — but far from the majority.
How Keytruda Works for Mesothelioma
Keytruda is a PD-1/PD-L1 checkpoint inhibitor drug. It interrupts the binding of the proteins PD-1 and PD-L1, the former on the immune system’s T-cells and the latter on mesothelioma cells.
Keytruda is FDA-approved for specific cases with high expression of PD-L1.
When these proteins connect, T-cells become ineffective at destroying cancer cells. Keytruda prevents the link and allows T-cells free reign to defend the body properly.
KEYNOTE-158 Study Results for Mesothelioma
In the KEYNOTE-158 study, participants received 200mg of Keytruda intravenously every three weeks, for up to 35 doses.
Of the 118 malignant pleural mesothelioma participants, 77 had PD-L1-positive mesothelioma. In theory, Keytruda should help in these cases.
Of those 77, just six (8%) had an objective response (either tumor stagnation or regression). The median response duration for these six was an impressive 17.7 months. This is a sign that when Keytruda works for mesothelioma, it works exceptionally well.
Keytruda generated an objective response in four of 31 (13%) patients with PD-L1-negative mesothelioma (meaning they didn’t have high levels of the protein). The median response duration was only 10.2 months, though, meaning Keytruda works for less time in PD-L1-negative cases.
The median overall survival among the 118 patients was 10 months, with a peak of 13.4 months. Chemotherapy, by comparison, leads to 12 months median survival in most studies.
By the end of the trial, 96% of the patients discontinued Keytruda, mostly due to disease progression. Of the five who continued the immunotherapy, there’s a good chance they were from the six PD-L1-positive cases with an objective response.
Sources & Author
- Efficacy and safety of pembrolizumab in patients with advanced mesothelioma in the open-label, single-arm, phase 2 KEYNOTE-158 study. The Lancelet. Retrieved from: https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30515-4/fulltext. Accessed: 04/08/2021.
Sources & Author