Expert Discusses Future of Immunotherapy in Lung Cancer

Heather A. Wakelee, MD

The treatment paradigm for non—small cell lung cancer (NSCLC) has entered a new era, Heather Wakelee, MD, associate professor of Medicine (Oncology) at Stanford University Medical Center, said in an interview with OncLive.

“With the advent of the checkpoint inhibitors, everything is changing for lung cancer,” said Wakelee. “We are now starting to think of all patients in terms of which immunotherapies will work in each context with each patient.”

Several new checkpoint inhibitors have recently been granted marketing authorization form the FDA, including pembrolizumab (Keytruda) and nivolumab (Opdivo), which are both approved for the treatment of patients with pretreated advanced NSCLC across all histologies.

The PD-L1 inhibitor atezolizumab (MPDL3280A) has also shown potential. Data presented at the 2015 European Cancer Congress demonstrated that when atezolizumab was added to chemotherapy in a phase Ib study, patients with newly diagnosed metastatic NSCLC had double the expected response.

OncLive: How has the treatment of lung cancer evolved in recent years?

In her Q/A with OncLive, Wakelee reflected on the evolution of lung cancer treatment and just how significant of an impact immunotherapies may have.Wakelee: Over the last 6 months alone, a whole new paradigm for treatment with immunotherapy has emerged in lung cancer. If we reflect on the previous decade, our focus has really been on molecularly targeted therapies. Fifteen years ago, no one would have ever conceived that we would be targeting treatment the way we are now. When EGFR first came about, we needed to think, all of a sudden, about every patient in the context of what their driver mutation is and determining how to treat that mutation.

What role do you envision for immunotherapies in lung cancer going forward?

We went from just chemotherapy, to the molecular focus, to now the immune focus. Along the way, we have not left chemotherapy or targeted therapy; however, we now have a third way of thinking about treatment.By just using them as single agents in patients who have already received chemotherapy, we are probably only helping 20% of patients. It is the combination of these therapies with each agent that is really the next wave. That's really one of the most promising fronts.

What are some of the biggest challenges that remain regarding the use of immunotherapies in lung cancer?

We also may be able to combine these agents with chemotherapy. Initially, the philosophy was, “If chemotherapy is going to suppress the immune system, we certainly don’t want to be combining it with immunotherapies, which are theoretically ramping up the immune system, because it could negate the effect.” However, the data that we have thus far actually look pretty encouraging for the chemoimmunotherapy combinations.Patient selection is a challenge. There is still a lot of controversy regarding this because we do not yet have a great biomarker. We have a biomarker for PD-L1 testing, but the nuances of it are such that there really isn’t one PD-L1 test. There are many different PD-L1 tests, and they do not all agree with each other. It can be difficult to determine which information is accurate. Even with the best assays, we are still excluding up to 10% or even more of patients who would benefit.

In the future, do you think immunotherapy will become a standard approach to the treatment of lung cancer?

Even with the selection, not everyone is benefitting. Therefore, it is a reasonable biomarker, but it is not a great one in the way we are used to thinking about with molecularly targeted therapy.That is going to be a part of the treatment paradigm for most patients. It is not that way now, but I think that’s where we are heading. The way that we’re going to get there is by combining therapies and finding better biomarkers.