- Medical Updates

Immune checkpoint inhibitors targeting programmed death protein 1 ( PD-1 ) receptor and its ligand, PD-L1, have recently led to significant and durable improvements in the clinical outcomes of some types of cancers including lung cancer.

Pembrolizumab ( Keytruda ) was approved for the treatment of advanced or metastatic non-small-cell lung carcinoma ( NSCLC ) whose disease has progressed after other treatments and with tumors that express PD-L1.

In the phase I KEYNOTE-001 trial, the overall response rate ( ORR ) was 19.4%, the median progression-free survival ( PFS ) and overall survival ( OS ) were 3.7 months and 12.0 months for 495 unselected patients with non-small-cell lung carcinoma.
Strong PD-L1 expression ( greater than or equal to 50% ) was associated with higher overall response rate, longer progression-free survival, and longer overall survival.

The phase II/III randomized KEYNOTE-010 trial demonstrated that Pembrolizumab improved overall survival versus Docetaxel ( Taxotere ) in patients with previously treated non-small-cell lung carcinoma.

Pembrolizumab has demonstrated durable response and prolonged overall survival especially in NSCLC patients with high expression of PD-1, thereby suggests a new treatment paradigm.
However, many issues remain to be explored, including the identification of other robust biomarkers that can accurately predict the immune-responsiveness of tumors.
Along with the identification of predictive biomarkers, further understanding of the tumor microenvironment is necessary to improve treatment outcomes through combinations of immunotherapy or combined with other targeted therapies. ( Xagena )

Lim SH et al, Expert Opin Biol Ther 2016; Epub ahead of print