Patients with squamous or non-squamous metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 and experience disease progression on or following the administration of platinum-containing chemotherapy, can now receive treatment with the drug pembrolizumab (Keytruda).
On October 2, 2015, the US Food and Drug Administration (FDA) granted accelerated approval for pembrolizumab. This monotherapy was also approved September 2014, for treatment of patients with advanced or unresectable melanoma who are no longer responding to other drugs.
Pembrolizumab blocks the PD-1/PD-L1 pathway, resulting in a disease-fighting immune response to kill malignant cells. Research showed that tumor size decreased in 41% of the patients who were treated with the drug. The effect of treatment was noted to last between 2.1 and 9.1 months.
PD-L1 expression is detected with the PD-L1 IHC 22C3 pharmDx test, which detects the expression of PD-L1 in non-small cell lung tumors.
"The durability of response with immune checkpoint inhibitors is exciting and has given new options for our patients," said Naiyer Rizvi, MD, director of thoracic oncology and director of immunotherapeutics, New York Presbyterian Hospital, Columbia University Medical Center, and a principal investigator for the Keytruda lung cancer clinical program, in a Merck press release. "And, with the approval of the first PD-L1 companion diagnostic, we can identify patients who are more likely to experience benefit from Keytruda."
The approved dose for pembrolizumab is 2 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks.
The most common side effects from pembrolizumab include:
- Fatigue (44%)
- Decreased appetite (25%)
- Dyspnea (23%)
- Cough (29%)
Other (more severe) adverse events reported include:
- Immune-mediated effects such as pneumonitis (3.5%), colitis (0.7%), hepatitis, hypophysitis (0.2%), hyperthyroidism (1.8%), hypothyroidism (6.9%), type 1 diabetes mellitus, and nephritis.
- And more clinically significant adverse events: rash, vasculitis, hemolytic anemia, serum sickness, myasthenia gravis, bullous pemphigoid, and Guillain-Barre syndrome.
It's also important to note that pembrolizumab should not be administered to pregnant or breastfeeding women.
Has anyone started using pembrolizumab in this particular lung patient population? If so, how are your patients responding?