The programmed death (PD-1) inhibitor pembrolizumab (Keytruda, Merck & Co) has been granted approval by the US Food and Drug Administration (FDA) for use in lung cancer, becoming the second immunotherapy available for this tumor type.
The accelerated approval is for use in patients with advanced non–small cell lung cancer (NSCLC) across all histologies whose disease has progressed on or after platinum-containing chemotherapy, as well as a targeted agent in epidermal growth factor receptor– or anaplastic lymphoma kinase–positive patients.
The PD-1 inhibitor was approved along with a companion diagnostic, the PD-L1 IHC 22C3 pharmDx test, which is the first test designed to detect PD-L1 expression in non–small cell lung tumors.
Today's approval was based in part on data from the KEYNOTE-001 trial, which led to the drug being granted a breakthrough therapy designation by the FDA in October 2014. The results showed that pembrolizumab had an overall response rate of nearly 20% among 495 previously treated and treatment-naive patients with advanced or metastatic NSCLC. The overall response rate was much higher, at 45.2%, among a cohort of patients with high PD-L1-expressing NSCLC.
The median duration of response exceeded 1 year (12.5 months) in all responders, regardless of the degree of PD-L1 expression. Median overall survival was 12.0 months (95% confidence interval [CI], 9.3 - 14.7 months) for all patients, 9.3 months (95% CI, 8.4 - 12.4 months) for previously treated patients, and 16.2 months (95% CI, 16.2 months - not reached) for previously untreated patients.
"Our growing understanding of underlying molecular pathways and how our immune system interacts with cancer is leading to important advances in medicine," said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research, in a statement. "Today's approval of Keytruda gives physicians the ability to target specific patients who may be most likely to benefit from this drug."
Breast-feeding or pregnant women should not take pembrolizumab because it may cause harm to the fetus or newborn baby, according to the FDA.
The most common adverse effects of Keytruda included fatigue, decreased appetite, shortness of breath or impaired breathing (dyspnea), and cough. Keytruda also has the potential to cause severe immune-mediated adverse effects.
Pembrolizumab is now the second FDA-approved PD-1 inhibitor in lung cancer and the first across all NSCLC histologies. The first immunotherapy for lung cancer to attain approval was nivolumab (Opdivo, Bristol-Myers Squibb), which has now shown a significant overall survival benefit compared with chemotherapy in two large phase 3 clinical trials.
It was approved in March 2015 for use in advanced/metastatic squamous NSCLC with progression on or after platinum-based chemotherapy. This approval was based on the CheckMate 017 study, which showed median OS of 9.2 months with nivolumab vs 6.0 months with docetaxel.
Nivolumab is also awaiting approval for use in nonsquamous NSCLC, based on the CheckMate 057 study, after having shown "unprecedented" survival, with a median overall survival of 12.2 months with nivolumab vs 9.4 months with docetaxel (hazard ratio, 0.73; P = .00155).
However, in these trials, the response to nivolumab did not appear to correspond with increasing levels of PD-L1 expression.
A number of other immunotherapies are also in late-stage development for use in lung cancer, including atezolizumab (previously known as MPDL3280A, under development by Genentech), from which phase 2 results were recently reported, and from which phase 3 results are awaited.
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Cite this: FDA Approves Pembrolizumab for Lung Cancer - Medscape - Oct 02, 2015.