It's also great news for the drug maker Merck, and it came at the ideal time; earlier the same day, the UK's Competition and Markets Authority accused the US-based pharma company of "offering unfair discounts" on infliximab, its blockbuster rheumatoid arthritis and Crohn's disease drug, to "discourage new competitors", according to the Financial Times. By blocking the interaction of PD-1 with PD-L1 and PD-L2, pembrolizumab releases PD-1 pathway-mediated inhibition of the immune response, including the antitumor immune response. In its second approval in a week, the FDA OKs the use of the PD-1 inhibitor to treat adult and pediatric patients with unresectable or metastatic solid tumors that are have a genetic profile called microsatellite instability-high (MSI-H) or mismatch fix deficient (dMMR).
The approval covers patients whose cancer has progressed despite prior treatment and those who have no satisfactory alternative treatment options.
The safety and efficacy of pembrolizumab for this indication was studied in patients with MSI-H or dMMR solid tumors who were enrolled in 1 of 5 uncontrolled, single-arm clinical trials. In some trials, patients were required to have MSI-H or dMMR cancers, while in other trials, a subgroup of patients were identified as having MSI-H or dMMR cancers by testing tumor samples after treatment began. The objective response rate was 36% in patients with colorectal tumors and 46% in patients with the 14 other tumor types.
The designation applies to use of pembrolizumab (Keytruda, Merck) - a humanized monoclonal antibody that blocks the interaction of PD-1 and its ligands - for patients who received at least two lines of chemotherapy.
Richard Pazdur, acting director of the Office of Hematology and Oncology Products in FDA's Center for Drug Evaluation and Research and director of the FDA's Oncology Center of Excellence, said: "This is an important first for the cancer community ..."
According to Pardoll, around 4 percent of advanced cancer cases, or up to 20,000 USA cases every year, have the genetic features involved in the FDA approval.
MSI-H/dMMR tumors are most often found in colorectal, endometrial or gastrointestinal cancers, the FDA said.
Patients were treated with 200-mg pembrolizumab every 3 weeks or 10-mg/kg pembrolizumab every 2 weeks until unacceptable toxicity or either symptomatic disease progression, rapid progression requiring urgent intervention, or progression with a performance status decline. Merck must still conduct studies to confirm the anticipated benefit.
The most common adverse reactions were fatigue, pruritus, diarrhea, decreased appetite, rash, pyrexia, cough, dyspnea, musculoskeletal pain, constipation, and nausea.
Merck's Keytruda, which works by harnessing the body's immune system to attack tumors, has previously been approved to treat several site-specific tumors, including those of the skin and lung.