Mark Socinski, MD
There is great enthusiasm about the role of immune checkpoint inhibitors in cancer treatment. The recent approval of nivolumab in the non–small cell lung cancer (NSCLC) setting marks a unique shift in the treatment landscape of this malignancy, one that harnesses the patient’s own immune system to target the tumors.
The challenge in using these agents, according to experts who participated in a recent OncLive
Peer Exchange program, is pinpointing ways of identifying which patients will reap the greatest benefit.
Led by moderator Mark A. Socinski, MD
, the panel of clinical and research experts discussed the burgeoning and evolving field of immunotherapy and personalized medicine during a Peer Exchange session entitled “Aiming for Precision Medicine in NSCLC.”
Immunotherapy: An Intuitive Approach
Thomas E. Stinchcombe, MD
Immunobiologists have successfully identified the underlying mechanisms related to tumor induced immune suppression on the infiltrating lymphocytes and immune cells in the tumor microenvironment. The understanding of these mechanisms has led to several therapeutic insights, including the programmed death receptor-1 (PD-1).
PD-1 is a type 1 transmembrane protein expressed on immune cells, and tumors can express the PD-1 ligands, PD-L1 and PD-L2. In general, tumor cells express PD-L1, which binds to PD-1, causing T cells not to attack the tumor. PD-1/PD-L1 inhibitors block this interaction, allowing for an immune response. Thus, the development of mechanisms to combat either PD-1 or PD-L1 intuitively makes sense.
Along with nivolumab, which was approved for NSCLC in March, a number of PD-1/PD-L1 checkpoint inhibitors are in clinical trials. These antibodies include pembrolizumab which, like nivolumab, targets PD-1, and MPDL3280A and MEDI4736, which are aimed at PD-L1.
These agents work by blocking the interaction between PD-1 and PD-L1. The data for these agents produce a consistent response rate ranging from 15% to 25%, Socinski noted. One of the remarkable things about the response, he added, is the durability of many of these responses.Thomas E. Stinchcombe, MD
, reviewed the findings from the phase II CheckMate-063 and the phase III CheckMate-017 trials, which led to the approval of singleagent nivolumab in heavily pretreated patients with advanced squamous cell NSCLC. In the CheckMate-063 trial, the objective response rate with nivolumab, at an 11-month follow-up, was 15%. The estimated 1-year survival rate was 41% and the median overall survival (OS) was 8.2 months.1
Additionally, CheckMate-017 demonstrated that nivolumab extended OS compared with docetaxel in patients with pretreated squamous cell NSCLC (Table)
“I think most of us are eagerly awaiting to see the full presentation of this data because it does have the potential to be a practice-changing trial,” said Stinchcombe.
Patterns of Response With Immunotherapy
Table. Survival Statistics in Pivotal Nivolumab NSCLC Trial2
NSCLC indicates non–small cell lung cancer.
While a subgroup of patients are reaping benefits from immunotherapy, one issue that oncologists must be cognizant of is pseudoprogression.Roy S. Herbst, MD, PhD
, and Heather A. Wakelee, MD
, discussed the phenomenon of pseudoprogression, during which 10% to 20% of tumors will grow before they start to shrink. They discussed strategies for assessing the difference between pseudoprogression and actual progression, including scans.
Roy S. Herbst, MD, PhD
Herbst also described how different patient and tumor characteristics, including smoking status, histologies, and mutations, might exhibit different responses to immunotherapy.
In contrast to the lack of success with many other current therapies, studies are finding activity with immunotherapy in patients with squamous lung cancer, who are smokers, and in tumors that harbor KRAS
mutations.Toxicities With Immunotherapy