This week, the United States Food and Drug Administration (FDA) approved the use of Keytruda (pembrolizumab) for the treatment of metastatic small cell lung cancer (SCLC). This is an exciting development, as treatment options and advancements are not as common for SCLC as they are for other cancers, including other lung cancers. Keytruda is intended to be used by individuals with metastatic small cell lung cancer who have had cancer progression after, or while taking, platinum-based chemotherapy. It is also intended to be used by individuals who have previously tried at least one other treatment option.
PD-1/PD-L1 and Keytruda
Keytruda is part of a specific drug category called anti-PD-1 therapy. Normally, in the body, PD-1 is a receptor found on the surface of certain immune cells that helps these cells communicate with one another. PD-1 can bind to another receptor called PD-L1 that can be on the surface of tumor cells, joining the immune cell and tumor cell together. When tumor cells have PD-L1 and this binding happens, the cancer cells may be able to avoid our naturally occurring, cancer fighting immune cells in the body.
Immunotherapy medications that focus on PD-1/PD-L1, like Keytruda, aim to block the cancer’s ability to use the PD-L1 it possesses to avoid our body’s natural cancer killing abilities. Keytruda helps certain immune cells, called T-cells, stay active against cancer cells that may try to suppress them. This may prevent the growth and development of tumor cells within the body. However, it’s possible that these active T-cells can attack other, normal tissues within the body, which may lead to several of Keytruda’s side effects. Some of these potential side effects include transplant rejection, changes in thyroid functioning, and inflammation of the colon, liver, lungs, and kidneys, among other potential issues.
What did the research show?
The approval of Keytruda for SCLC was made based on the results of two multicenter, multi-cohort, non-randomized clinical trials called the KEYNOTE-158 and KEYNOTE-028 trials. The participants involved in the study all had SCLC that progressed while on, or after, platinum-based chemotherapy, and who had previously tried at least one other treatment option before Keytruda. In total, 83 individuals were included in the study and received Keytruda in a 200 mg intravenous dose once every three weeks, or a 10 mg/kg dose intravenously every two weeks. Over 60% of participants had tried two different therapies before Keytruda, and over 30% had tried three or more. Additionally, 60% of participants had past thoracic radiation (radiation to the chest region) and over 50% had past brain radiation for the treatment of their metastatic SCLC.
In the trials, Keytruda treatment was continued for 24 months, or until an unacceptable adverse effect or cancer progression occurred. The researchers measured objective response rate (ORR) and duration of response (DOR) using a modified measurement tool called the Response Evaluation Criteria in Solid Tumors (RECIST). Overall, the results suggested that there was a 19% ORR for those taking Keytruda, with 17% having a partial response, and 2% having a complete response. Almost 95% of participants given Keytruda had a DOR of six months or longer, while 63% and 56% had a DOR of 12 months or longer and 18 months or longer, respectively. The longest measured DOR was 35.8+ months, and the shortest was 4.1 months. These response rates suggest that Keytruda may be an effective treatment option for those with SCLC. More studies are needed to determine the full benefits of Keytruda for this group.
Common side effects
Keytruda has previously been approved for the treatment of other solid tumors, and the safety and adverse effects found during this study were similar to those found for other types of cancer treated with Keytruda. The most common side effects of Keytruda were fatigue, itching, nausea, constipation, cough, changes in thyroid functioning, and decreased appetite. Keytruda was recently approved for use in non-small cell lung cancer (NSCLC) as well and is made by Merck & Co.
FDA Approves Merck’s KEYTRUDA® (pembrolizumab) as Monotherapy for Patients with Metastatic Small Cell Lung Cancer (SCLC) with Disease Progression on or After Platinum-Based Chemotherapy and at Least One Other Prior Line of Therapy. Merck & Co. https://www.mrknewsroom.com/news-release/prescription-medicine-news/fda-approves-mercks-keytruda-pembrolizumab-monotherapy-patie. Published June 18, 2019. Accessed June 19, 2019.
FDA Approves Pembrolizumab for Metastatic Small Cell Lung Cancer. U.S. FDA. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-metastatic-small-cell-lung-cancer. Published June 18, 2019. Accessed June 19, 2019.
Columbus, G. Pembrolizumab Approved by FDA for Previously Treated Metastatic SCLC. https://www.targetedonc.com/news/pembrolizumab-approved-by-fda-for-previously-treated-metastatic-sclc. Published June 18, 2019. Accessed June 19, 2019.