Novel Agents Continue to Make Mark in Lung Cancer

Mark B. Stoopler, MD

The armamentarium of non—small cell lung cancer (NSCLC) treatments has had a dramatic shift toward personalized medicine in recent years, and pivotal ongoing research could individualize it even further.

In 2016 alone, there were several practice-changing decisions. In March, the FDA approved crizotinib (Xalkori) as a treatment for patients with ROS1-positive metastatic NSCLC.

In April, the EGFR inhibitor afatinib (Gilotrif) was approved by the FDA for the treatment of patients with advanced squamous NSCLC following progression on platinum-based chemotherapy.

On the immunotherapy front, the PD-1 inhibitor pembrolizumab (Keytruda) was granted a frontline indication in October 2016 for patients with NSCLC who have greater than 50% PD-L1 expression levels and do not harbor EGFR or ALK abnormalities, in addition to its second-line and beyond approval granted by the FDA in 2015. In the latter approval, patients with NSCLC had PD-L1 expression levels of greater than 1% and progressed on platinum-based chemotherapy and EGFR- or ALK-targeted therapy.

Also in October 2016, the FDA approved atezolizumab (Tecentriq), a PD-L1 inhibitor, as a treatment for patients with metastatic NSCLC who have progressed after a platinum-containing regimen and an FDA-approved targeted therapy for those patients who have EGFR or ALK abnormalities.

OncLive: What did you highlight in this case discussion at the State of the Science Summit on NSCLC?

What are the most important, and current, developments taking place in lung cancer?

Mark B. Stoopler, MD, medical oncology, internal medicine, NewYork-Presbyterian Hospital, was part of a panel discussion during the 2017 OncLive^® State of the Science Summit on Advanced Non—Small Cell Lung Cancer. In an interview at the meeting, he discussed ongoing developments in immunotherapy and his vision for the future of NSCLC treatment.Stoopler: I was part of a panel that presented several interesting cases related to lung cancer. My particular case concerned a patient with sarcomatoid carcinoma of the lung, which is a rare and very aggressive type of lung cancer, for which there haven’t been good treatments in the past. This is because it is a chemotherapy-resistant disease. However, we are now learning that this disease often has genomic alterations and high PD-L1 expression levels, which might make it very amendable to therapy with immunotherapy drugs. Moreover, this patient in particular had amazing response—in a very desperate situation—and is actually doing very well. Unquestionably, the development of many immunotherapy drugs has totally changed the scope, at least for a percentage of patients. It is certainly not for everyone. But, in addition to that, the personalized approach to discovering the genetic mutations that might be driving that particular patient's tumor hasn’t really changed things for another group substantial group of patients.

Speaking of sequencing, how do you typically decide which agent to give in each line of therapy?

What are some ongoing clinical trials in the field of NSCLC that you are anticipating the results of?

What are the main points of your discussion that you hope community oncologists will take away and apply to clinical practice?

Every year, there seems to be more targets that we have that we can gear our therapies towards. We are seeing patients who, in the past, would have predicted to only have 6 to 12 months of survival left. Now, they are sometimes living years with a sequence of treatments. It depends upon what target is present in that patient's particular tumor. If there is a mutation that we can target with an oral therapy, that usually is the first priority to use that kind of treatment. If there isn't, then either chemotherapy or immunotherapy might be used, partly depending on the PD-L1 expression level. I am interested in seeing the results of the combination immunotherapy trials, which have the potential to improve response rates. Perhaps they could even improve duration of response. The main takeaway for oncologists in practice is to be sure that the patient has had their tumor appropriately tested with genetic profiling and PD-L1 testing. That way, we are never missing an opportunity for an effective treatment.