If you are a mesothelioma patient or a loved one of a mesothelioma patient, you know how essential clinical trials can be. Clinical trials offer an opportunity for potentially more effective treatment for the individual mesothelioma patient, as well as the opportunity to contribute to the larger effort to beat mesothelioma once and for all.
Clinical trials are especially appealing to mesothelioma patients, as many are diagnosed in the later stages of the disease, significantly narrowing their treatment options. Clinical trials give patients and their loved ones the chance to expand their arsenal in the fight against mesothelioma, an opportunity which many going through mesothelioma treatment enthusiastically embrace. Trials already in progress offer new information and hope for mesothelioma patients and their families about potential treatments and improved prognoses on the horizon.
One such clinical trial conducted recently on a new mesothelioma treatment has been very promising. The study, conducted by the Netherland Cancer Institute in Amsterdam, tested the combination of Keytruda (pembrolizumab) and Lenvatinib (sometimes known as Lenvima) as a second-line treatment (a treatment to use when the first recommended treatment isn’t working) for pleural mesothelioma.
Keytruda is a humanized antibody and immunotherapy treatment used to combat a wide range of cancers, and Lenvatinib is a multiple kinase inhibitor, which blocks cancer proteins. The study examined the use of both medications, and the ways that their combined effects may be helpful for mesothelioma patients.
The findings were presented at the IASCL 2022 World Conference on Lung Cancer in Vienna, Austria earlier this summer. One of the lead investigators of the study, Li-Anne Douma, represented the research team in presenting the results to the Conference, and called the findings “better than expected.”
For those new to the subject, clinical studies have four phases. Phase I, which was already completed for this treatment, tested for basic safety of the treatment in humans, ensuring that it is not widely lethal and there are relatively limited serious adverse health effects.
Phase II focuses on the effectiveness of the treatment and the best dosage and delivery method, as well as any potential side effects. That is the phase of treatment that was just completed by the researchers at the Netherlands Cancer Center.
If approved, Phase III of the study will be much larger, and will likely involve volunteers from diverse population sets. It will examine whether the treatment would be both safe and effective for a wide variety of people, gathering more information about potential combinations of treatments, different dosages, and other different treatment components.
If results are promising enough, the treatment may then be approved for a New Drug Application (NDA), which contains the research, data, and findings from all phases. If the FDA (or a similar European regulatory body) signs off on the NDA, the treatment combination will become available on the market.
Phase IV will then occur after the introduction of the treatment to the market, during which researchers will continue to gather data and monitor the treatment as it is applied in much larger and more diverse populations, looking out for any potentially serious health complications that may only arise when larger populations are involved.
As aforementioned, the Netherland Cancer Institute study on Keytruda/Levatinib treatment for pleural mesothelioma is still in Phase II of clinical testing. This round of testing was conducted on 38 patients whose mesothelioma had continued to progress even after receiving standard-of-care treatment (chemotherapy). The study examined the use of Keytruda, which has been well-received in the treatment of several different cancers since it was approved for use in 2020 but has only shown limited success as a sole treatment method (or, as a “monotherapy”) for mesothelioma. Only around 20% of mesothelioma patients were responsive to monotheraputic treatment with Keytruda.
It was hypothesized that what Keytruda needed was an “effective drug partner”, for a combined, interactive effect, or “synergy.” That’s what Lenvatinib was brought in to do. Lenvatinib, which was originally developed to treat thyroid cancer, has been shown to be effective in blocking tumor growth. It is usually prescribed as a monotreatment for hepatocellular carcinoma (a type of liver cancer), and in conjunction with other drugs to treat renal cell carcinoma (a type of kidney cancer).
Lenvatinib is known as “precision medicine”, because it excels at doing something specific (i.e., blocking the growth of tumors) in a limited set of contexts. This study used Lenvatinib’s precision abilities as a partner to Keytruda, treating mesothelioma by targeting certain types of proteins that Keytruda is normally unable to control on its own.
The Keytruda/Lenvatinib combo has already been shown to be effective and has been approved for use in the treatment of endometrial cancer. The hope of the clinical trial was that it could be similarly helpful for the treatment of pleural mesothelioma.
The results were objectively impressive: combined Lenvatinib/Keytruda treatment had a response rate of 58%, which is significantly higher than Keytruda’s monotherapy response rate of around 20%.
Douma stated that she and her team would “like to avoid conclusions being drawn too early”, which is prudent for any study. It should be noted that there is still no effective long-term treatment for most mesothelioma patients. However, the possibility of another helpful second-line treatment for pleural mesothelioma is a source of hope for patients and their families.
If approved for widespread use, the Levatinib/Keytruda treatment would join the quickly increasing roster of potential mesothelioma treatments: in 2020, another immunotherapy combination treatment—Opdivo and Yervoy—was approved for use as a first-line treatment, adding to former standard of care (which until that time, for most mesothelioma patients, included only chemotherapy).
While larger trials and further research is still needed, this development is widely considered to be good news for the mesothelioma community.