The U.S. Food and Drug Administration today granted accelerated approval for Keytruda (pembrolizumab) to treat patients with advanced (metastatic) non-small cell lung cancer (NSCLC) whose disease has progressed after other treatments and with tumours that express a protein called PD-L1. Keytruda is approved for use using a companion diagnostic, the PD-L1 IHC 22C3 pharmDx evaluation, the first test designed to find PD L1 expression in non-small cell lung tumours.
Lung cancer is the leading source of cancer death in the United States, with diagnoses and 158,040 new an estimated 221,200 , according to the 2015 departures in National Cancer Institute. NSCLC is the most common form of lung cancer.”Our growing understanding of underlying molecular pathways and how our immune system interacts with cancer is leading to significant advances in medicine,” said Richard Pazdur, M.D., manager of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Now’s acceptance of Keytruda gives physicians the capability to target particular patients who may be most likely to reap the benefits of this drug.”
Keytruda operates by targeting the cellular pathway called PD-1/PD-L1 (proteins found on the body’s immune cells and some cancer cells). Keytruda may help the body’s immune system fight the cancer cells by blocking this pathway. In 2014, Keytruda was approved to take care of patients with advanced melanoma following treatment with ipilimumab, a form of immunotherapy. Another drug, Opdivo (nivolumab), made by Bristol-Meyers Squibb, also targets the PD-1/PDL1 pathway and was approved to treat squamous non-small cell lung cancer (a certain type of NSCLC) in 2015.
The security of Keytruda was analyzed in 550 patients with advanced NSCLC. The most common side effects of Keytruda contained tiredness, reduced appetite, shortness of breath or impaired breathing (dyspnea) and cough. Keytruda additionally has the capacity to cause severe side effects that result from the immune system effect of Keytruda (known as “immune-mediated side effects”).
The effectiveness of Keytruda for this use was presented in a subgroup of 61 patients enrolled in a larger facility, open-label, multi-part study. The subgroup consisted of patients with advanced NSCLC that progressed following platinum-based chemotherapy or, if appropriate, targeted treatment for certain genetic mutations (ALK or EGFR). This subgroup also had PDL1 positive tumours predicated on the outcomes of the 22C3 pharmDx diagnostic test. Study participants received 10 mg/kg of Keytruda three or every two weeks. The important outcome measure was general response rate (percent of patients who experienced complete and partial shrinkage of their tumors). Tumors shrank in 41 percent of patients treated with Keytruda and also the effect continued between 2.1 and 9.1 months.
In the 550 study participants with advanced NSCLC, severe immune-mediated side effects occurred involving the lungs, colon and hormone-producing glands. Other uncommon immune-mediated side effects were rash and inflammation of blood vessels (vasculitis). Because it may cause harm to a developing fetus or newborn baby, women who are breastfeeding or indeed pregnant shouldn’t take Keytruda. Across clinical studies, a disorder in which the body’s immune system attacks part of the peripheral nervous system (Guillain-Barre Syndrome) additionally happened.
The FDA gave Keytruda breakthrough treatment designation for this indicator because Merck attested through preliminary clinical signs that the drug may provide a considerable improvement over available therapiesreatments. The drug also received priority review status, which is granted to drugs that, at the time the application was submitted, possess the capacity to be an important improvement in safety or effectiveness in the therapy of a serious affliction.
Keytruda was approved under the agency’s accelerated approval program, which enables the approval of a drug to treat a serious or life-threatening disease predicated on clinical data demonstrating the drug has an effect on a surrogate endpoint reasonably likely to predict a clinical benefit to patients. While confirmatory clinical trials are conducted by the company, this program supplies earlier patient access to promising new drugs. An improvement in survival or disease-associated symptoms in patients being treated with Keytruda has not yet been established.
Keytruda is marketed by Merck & Co., based in Whitehouse Station, New Jersey and the PD-L1 IHC 22C3 pharmDx diagnostic test is marketed by Dako North America Inc. in Carpinteria, California.
Lung cancer is the No. 1 cancer killer, with 221,200 new cases and 158,000 deaths anticipated this year in the U.S., according to the National Cancer Institute.
Article by Erica Woo
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