by Dr. C.H. Weaver M.D. updated 6/2019
Updated findings from the phase 1b KEYNOTE-028 study investigating the use of Keytruda® (pembrolizumab) in small cell lung cancer (SCLC) were recently presented at the 17th World Conference on Lung Cancer. and led to the US Food and Drug Administration's approval.
Lung cancer remains the leading cause of cancer-related deaths worldwide. In the United States, SCLC accounts for 10-20% of all lung cancers. Although progress has been made in recent years, the majority of patients with advanced stage lung cancer still die from their disease. New treatments are needed.
Precision medicine continues to impact the lives of lung cancer patients with research into genomics and genetics leading to unprecedented progress in improving outcomes. Tailored treatments have emerged to match a person’s genetic makeup or a tumor’s genetic profile. As a result, patients with lung cancer now typically receive molecular testing that guides their physicians in determining which therapies are more likely to boost the chances of survival while limiting the potential for adverse effects.
Results from studies evaluating immunomodulatory approaches using anti-PD-1 and anti-PD-L1 antibodies have demonstrated promising results and are advancing the standard of care for lung cancer. PD-1 is a protein that inhibits certain types of immune responses. Drugs that block PD-1, such as Keytruda may enhance the ability of the immune system to fight cancer.
KEYNOTE-028 is an ongoing early stage clinical trial evaluating the safety, tolerability, and anti-tumor activity of Keytruda in more than 450 patients with PD-L1 positive cancers.
The overall response rate (ORR) and duration of response is reported to be 19% with a complete response rate of 2%. Responses were durable for 6 months or longer in 94%, 12 months or longer in 63%, and 18 months or longer in 56% of the 16 responding patients.
The recommended Keyturda dose for SCLC is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Dr. Patrick Ott from the Dana-Farber Cancer Institute had previously reported a response rate of 33.3 percent including one complete response and seven partial responses.
Keytruda was well tolerated and reported side effects were consistent with that observed in previously reported studies. “These long-term data, which show meaningful response rates and durable responses in certain patients with small cell lung cancer, are encouraging,” said Dr. Ott. “With these findings, we are advancing understanding of the potential for immunotherapy to make a difference for these patients.”
A larger trial, KEYNOTE-158, has been initiated to further evaluate Keytruda in advanced SCLC and malignant pleural mesothelioma.
Reference: Ott P, Felip E, Hiret S, et al. Pembrolizumab in Patients with Extensive-Stage Small Cell Lung Cancer: Updated Survival Results from KEYNOTE-028. Presented at the 17th World Conference on Lung Cancer. December 4-7, 2016. Vienna, Austria. Abstract #OA05.01.