It always seemed like a matter of when — not if — Keytruda would be approved for mesothelioma.
The “when” is now here — but only for some mesothelioma patients.
The United States Food and Drug Administration (FDA) approved the brand-name immunotherapy drug for specific cases of pleural mesothelioma, among other solid-tumor cancers. Keytruda is the brand name of the drug pembrolizumab, which has been featured in a number of mesothelioma clinical trials.
The FDA’s approval occurred Tuesday, June 16, 2020. This date is a little more than one year after the FDA granted approval for a tumor treating fields device for pleural mesothelioma. The NovoTTF-100L System device, which has been rebranded Optune Lua, received FDA approval in May 2019 for specific cases of pleural mesothelioma.
If you have pleural mesothelioma and wish to learn if you’re eligible for the FDA’s Keytruda treatment guidelines, email our patient advocates. Karen Ritter (firstname.lastname@example.org) can help you get in touch with one of the many cancer centers around the country to learn your options in fighting your diagnosis.
Details of FDA’s Approval of Keytruda for Mesothelioma
Keytruda’s approval is also based around specific cases: metastatic (spreading) or unresectable mesothelioma, with no other treatment options. The FDA granted approval for Keytruda in cases where the mesothelioma has progressed “following prior treatment.”
The approval is also based around arguably the most important aspect: tumor mutational burden, which is often shortened to the acronym TMB. The approval is for cases involving tumor mutational burden-high (TMB-H). In mesothelioma, the high TMB is due to high levels of PD-L1.
High expression of this protein is common in mesothelioma. The PD-L1 protein receptor interacts with the human body’s T-cells, which have PD-1 proteins and receptors. When these two receptors connect, the T-cells dismiss the mesothelioma cells as harmless. The immune system is subdued, and tumors are allowed to grow and spread without much resistance.
Mesothelioma immunotherapy treatment may help address this issue.
Keytruda is a checkpoint inhibitor immunotherapy drug that targets the PD-L1/PD-1 pathway. Keytruda is the medicinal blockade that prevents these receptors from connecting, which helps the T-cells clearly see mesothelioma cells as dangerous.
The FDA’s approval comes on the heels of a recent study involving Keytruda for TMB-H cancers. There were 102 participants meeting this characteristic, and the overall response rate among them was 29%. The researchers broke down the details of the responses among the TMB-H population:
- 24% had a partial response (meaning their disease shrunk slightly).
- 5% had a complete response (meaning their disease shrunk significantly, or completely).
The study also compared how Keytruda helped TMB-H patients and non-TMB-H patients:
- 26.4% of TMB-H patients had progression-free survival for one year, compared to just 14% of the non-TMB-H patients.
- 18.9% of TMB-H patients had progression-free survival for two years, compared to just 6.5% of people with non-TMB-H cancers.
Not all specialists believe immunotherapy drugs like Keytruda are a saving grace for mesothelioma. Dr. Raja Flores, the chief thoracic surgeon at Mount Sinai Hospital in New York, said there is disappointment in Keytruda’s effect on mesothelioma.
“Surgery still is the most effective treatment to reduce tumor volume,” Dr. Flores said.
In the reported Keytruda study, median overall survival was actually higher (13 months versus 11.7 months) for the non-TMB-H group. However, people with TMB-H cancers had a better chance of lengthy survival: Around 34% survived for two years, compared to just 31% of non-TMB-H patients.
Unfortunately, TMB-H was not common among the mesothelioma patients in this study. This rare cancer was the most common of the non-TMB-H group, accounting for 12.7% of those patients. Most mesothelioma cases do not have high TMB due to not expressing a significant amount of the PD-L1 protein.
Dr. Marwan Fakih, the lead investigator of the trial, spoke to the website Targeted Oncology about the FDA’s approval of Keytruda.
“I believe the FDA made the right decision to approve pembrolizumab based on these findings,” said Dr. Fakih, who’s also a medical oncologist at the City of Hope Cancer Treatment and Research Center in California.
“However, much still needs to be learned regarding the extent of benefit within each of these tumor types and others.”
In 2019, Keytruda was the focus of a phase 3 clinical trial. The results were discouraging, with patients receiving the treatment having a median survival of 10.7 months. By comparison, the group of people receiving just chemotherapy survived for 11.7 months.
Still, many specialists and researchers kept hope in Keytruda for mesothelioma.
“Don’t give up on immunotherapy,” Dr. Ezra Cohen, a medical oncologist who treats pleural mesothelioma, said at that time. “There is that initial disappointment. … It’s just a matter of figuring it out.”
In 2019, Mesothelioma Guide welcomed Dr. Cohen on a podcast to discuss immunotherapy for mesothelioma.
Keytruda received its first FDA approval in 2017 for non-small cell lung cancer. This cancer type had the largest percentage of TMB-H patients in the aforementioned study. Keytruda has since been approved for other specific cancers.
Sources & Author
- FDA approves pembrolizumab for adults and children with TMB-H solid tumors. U.S. Food and Drug Administration. Retrieved from:
https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-adults-and-children-tmb-h-solid-tumors. Accessed: 06/17/2020.
- FDA Approves Pembrolizumab for TMB-High Solid Tumors. Targeted Oncology. Retrieved from:
https://www.targetedonc.com/view/fda-approves-pembrolizumab-for-tmb-high-solid-tumors. Accessed: 06/17/2020.
- FDA Approves Second Biomarker-Based Indication for Merck’s KEYTRUDA® (pembrolizumab), Regardless of Tumor Type. Merck. Retrieved from:
https://investors.merck.com/news/press-release-details/2020/FDA-Approves-Second-Biomarker-Based-Indication-for-Mercks-KEYTRUDA-pembrolizumab-Regardless-of-Tumor-Type/default.aspx. Accessed: 06/18/2020.
Sources & Author