From just chemotherapy to molecular and immune focused therapies, the landscape of non-small cell lung cancer (NSCLC) has drastically changed over the course of the last 10 years according to Heather Wakelee, MD.
Heather Wakelee, MD
From just chemotherapy to molecular and immune focused therapies, the landscape of treatment for nonsmall cell lung cancer (NSCLC) has drastically changed over the course of the last 10 years according to Heather Wakelee, MD.
“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,” said Wakelee, MD, associate professor of Medicine (Oncology) at Stanford University Medical Center. “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.”
Wakelee adds that checkpoint inhibitors have also changed the game for NSCLC treatment, citing the inhibitors have made medical professionals start to think of all patients in terms of which immunotherapies will work in each context with each patient.
She also points out that when immunotherapies are used in combination with chemotherapy, the benefit to patients is great.
“By just using [immunotherapies] 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,” she said. “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.”
In 2015 alone, the FDA has authorized marketing for checkpoint inhibitors such as pembrolizumab (Keytruda) and nivolumab (Opdivo) to be used in treatment of patients with pretreated advanced NSCLC across all histologies. Alongside these treatments is also the PD-L1 inhibitor atezolizumab (MPDL3280A), whose data was presented at the 2015 European Cancer Congress. The presentation showed that patients with newly diagnosed metastatic NSCLC had double the expected response when atezolizumab was added to chemotherapy in a phase Ib study.
Regarding challenges in the future treatment of lung cancer with immunotherapies, Wakelee cites the nuances of biomarkers and getting the paradigm of treatment right for patients.
“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,” she said. “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.”