Immune System-Boosting Drugs, New and Old, Are Explored in Combination Treatments for Lung Cancer

Readers of this blog will already know a thing or two about immunotherapy (immune system-activating drugs) and targeted therapy in lung cancer. Both approaches have benefited many patients in recent years. Now, research is being done to combine immunotherapies with other types of drugs. Of particular interest are immunotherapies that target PD-1, PD-L1, and CTLA4. These drugs, also known as immune checkpoint antibodies, are being tested in combination with other drugs in patients participating in the clinical trials below. Continue reading…

ESMO 2014: Pembrolizumab Shows Promise in Several Solid Tumours

The gist: A new drug called pembrolizumab has shown promise for treating several cancer types, including melanoma and non-small cell lung cancer (NSCLC). Pembrolizumab is an immunotherapy, meaning that it boosts a patient’s own immune system to fight cancer. It has been tested in several clinical trials—research studies with volunteer patients. In one trial, pembrolizumab showed benefits for advanced NSCLC patients. It might be particularly effective for patients whose tumors have high expression of the protein PD-L1. There are ongoing pembrolizumab clinical trials that NSCLC patients can enroll in. Another clinical trial compared different pembrolizumab dosing schedules for melanoma patients. In fact, pembrolizumab, also known as Keytruda, has already been approved by the U.S. Food and Drug Administration (FDA) for certain kinds of melanoma patients.

“Results from the studies of pembrolizumab in advanced non-small-cell lung cancer (NSCLC), melanoma, gastric cancer, urothelial cancer and head and neck carcinoma, presented during the ESMO 2014 Congress (Madrid, Spain), show promising activity and tolerability from this novel monoclonal antibody.

“PD-1 is a negative co-stimulatory receptor expressed primarily on activated T cells. Binding of PD-1 to its ligands inhibits effector T-cell function. Expression of PD-L1 on tumour cells and macrophages can suppress immune surveillance and permit neoplastic growth.

“Pembrolizumab is able to achieve a dual blockade (PD-L1 and PD-L2). It shows no cytotoxic (ADCC/CDC) activity. Pharmacokinetics support dosing every 2 weeks (Q2W) or every 3 weeks (Q3W). Pembrolizumab demonstrated a clinical activity in multiple tumour types…

“The anti-PD-1 antibody pembrolizumab has shown durable antitumour activity and acceptable toxicity in treatment-naïve and previously treated advanced NSCLC patients. Correlation between tumour PD-L1 expression and improved pembrolizumab antitumour activity has been observed. Prof. Edward Garon of the David Geffen School of Medicine at UCLA, Santa Monica, USA presented analysis in 282 patients with treatment-naïve or previously treated advanced NSCLC enrolled in randomised and non-randomised cohorts of the phase I KEYNOTE-001. The results were presented during the Proffered Paper session in metastatic NSCLC.”

FDA Approves Keytruda for Advanced Melanoma

Editor’s note: Before a drug can be widely prescribed in the U.S., it must first be tested in humans and then approved by the U.S. Food and Drug Administration (FDA). Today, the FDA approved a new drug for treating melanoma. The drug is called Keytruda (pembrolizumab). It is for people with melanoma that is advanced or unresectable (can’t be removed by a surgeon) and is not responding well to other drugs. Keytruda is an “anti-PD-1″ immunotherapy drug that boosts a patient’s own immune system to fight cancer. It works by targeting an immune system molecule called PD-1 that can keep the immune system from attacking tumors. It is now the first anti-PD-1 drug to be approved.

“The U.S. Food and Drug Administration today granted accelerated approval to Keytruda (pembrolizumab) for treatment of patients with advanced or unresectable melanoma who are no longer responding to other drugs.

“Melanoma, which accounts for approximately 5 percent of all new cancers in the United States, occurs when cancer cells form in skin cells that make the pigment responsible for color in the skin. According to the National Cancer Institute, an estimated 76,100 Americans will be diagnosed with melanoma and 9,710 will die from the disease this year.

“Keytruda is the first approved drug that blocks a cellular pathway known as PD-1, which restricts the body’s immune system from attacking melanoma cells. Keytruda is intended for use following treatment with ipilimumab, a type of immunotherapy. For melanoma patients whose tumors express a gene mutation called BRAF V600, Keytruda is intended for use after treatment with ipilimumab and a BRAF inhibitor, a therapy that blocks activity of BRAF gene mutations.”