Checkpoint Inhibitors Nivolumab and Pembrolizumab Gain Traction in NSCLC Treatment

December 1, 2015
Greg Kennelty

The PD-1 inhibitors pembrolizumab and nivolumab should be considered for all patients with advanced NSCLC, said Roman Perez-Soler, MD.

"I will give nivolumab or pembrolizumab [to patients with NSCLC] because I have to because it is the best I have." - Roman Perez-Soler, MD

Roman Perez-Soler, PhD

The PD-1 inhibitors pembrolizumab (Keytruda) and nivolumab (Opdivo) should be considered for all patients with advanced non—small cell lung cancer (NSCLC), especially in the second-line setting, said Roman Perez-Soler, MD.

"These drugs have been a gift for thoracic oncologists," said Perez-Soler, chairman of the Department of Oncology and chief of the Division of Medical Oncology at Montefiore Medical Center, Albert Einstein College of Medicine of Yeshiva University, in an interview withTargeted Oncologyat the 10th Annual New York Lung Cancer Symposium. "Because of these drugs our patients are going to live significantly longer. Our tool bag is now much more interesting. We used to have just a hammer and a screwdriver, now we have all sorts of tools."

As it currently stands, nivolumab is approved by the FDA as a second-line therapy for patients with NSCLC regardless of PD-1 expression levels. The approval was based on data from the phase III CheckMate-057 trial, where at the end of an 18-month analysis it was shown that the overall survival (OS) rate with nivolumab was 28%, versus 13% with docetaxel, in patients with squamous NSCLC.

Pembrolizumab has also been approved by the FDA, though for pretreated patients with advanced PD-L1-positive NSCLC with a companion diagnostic being the PD-L1 IHC 22C3 pharmDx test. A ≥50% PD-1 expression level in patients is currently requisite to receive pembrolizumab.

Contrasting that requirement, Perez-Soler says the recent KEYNOTE-10 study could change that. In the study, pembrolizumab was compared to docetaxel in patients expressing PD-L1 on >1% of their tumor cells. Researchers then assessed a subgroup of "strongly PD-L1—positive" patients defined as those expressing PD-L1 on ≥50% of their tumor cells.

"At this point pembrolizumab is tied to a biomarker test, but the new KEYNOTE-10 trial shows that the benefit is for all patients with above 1% PD-1 expression, so I think they are going to change that," he said. "The FDA is going to say that pembrolizumab is approved for patients with more than 1%. This will greatly increase the amount of patients that can receive this drug."

Data from the study showed an improved OS rate in both groups, as well as a better progression-free survival (PFS) in high PD-L1 expressing patients. In patients with <50% PD-L1 expression, PFS was improved with pembrolizumab, but the data was not statistically significant.

"One question that comes up is 'can we exclude any patients from treatment with these drugs?'' The answer is no. The reason is because patients with no expression of PD-L1 in the tumors, still respond, not as often, but there is an 8% to 10% response rate and some of these responders are really strong. We don’t understand why that is but it is the reality," said Perez-Soler.

"Patients typically progress in two or three months. The initial drugs, typically chemotherapy, shrink the tumor but then it comes back and the same drug cannot kill it. The most important thing now is to try and move these therapies to the frontline because they are non-toxic and might be more effective. These therapies could also be used in combination with chemotherapy. That has been studied and so far the results look fairly promising."

Perez-Soler says despite both nivolumab and pembrolizumab being viable options in patients with NSCLC, there is no clear evidence on which is a better treatment. He adds ultimately, oncologists should rely on personalizing treatments for each patient and use one of the two drugs accordingly.

"At this point, I would suggest that oncologist could use either of them. We should wait for the superiority trials to tell us one is better than the other because it has been proven with an experiment," he said. "We need evidence. It may be that all are equally good and then we will not need to choose one over the other. One drug is given every 3 weeks [pembrolizumab] and one is given every 2 weeks [nivolumab], so perhaps if they are proven to be equal that may prove to be the most important factor in the end."