Expert Explains Keys to Additional Advances in Lung Cancer

Edgardo S. Santos, MD

The field of lung cancer has undoubtedly seen notable advances over the past year—especially with the game-changing November 2016 approval of pembrolizumab (Keytruda) for the frontline treatment of patients with non—small cell lung cancer (NSCLC).

However, Edgardo S. Santos, MD, explains that the research to improve outcomes for patients with NSCLC has only just begun. Developing treatments to target additional pathways, refining PD-L1 use as a biomarker for anti—PD-1/PD-L1 agents, and identifying new biomarkers for patient selection are critical steps needed to build on the foundation of recent advances.

Santos, the medical director for Cancer Research at Lynn Cancer Institute, Boca Raton Regional Hospital, and associate professor of Biomedical Clinical Medicine at Charles E. Schmidt College of Medicine, Florida Atlantic University, discussed ongoing developments in the field at the 2016 OncLive State of the Science Summit on Advanced Non—Small Cell Lung Cancer.

OncLive: What did you highlight in your presentation at the meeting?

What are the most important points for community oncologists to take away from your lecture?

In an interview at the meeting, he discussed the recent landmark progression in lung cancer and the next steps needed to solve unmet challenges.Santos: I discussed what, who, when, and how to treat patients with lung cancer. What are the biomarkers that will provide patients the opportunity to receive either targeted therapy or immunotherapy? I also focused on PD-L1 testing, which is a very exciting topic now in oncology—especially after the phase III clinical trial with pembrolizumab, known as KEYNOTE-024, was positive for improving overall survival in frontline versus chemotherapy.Our focus was to emphasize the importance of testing for, at least, the 4 biomarkers that the NCCN now recommends in its guideline. Those biomarkers are EGFR, ALK, ROS1 and PD-L1. PD-L1, although it is not a perfect biomarker, is the one that has shown in several clinical trials to perhaps be the best tool we have right now to predict which patients will respond better to immunotherapy versus chemotherapy.

What are some of the most exciting advancements in the field?

The other thing to note is how important it is to recognize the acquisition of a good biopsy. By obtaining a good biopsy by different methods—either surgery, bronchoscopy, or a circulating tumor cell-guided biopsy—the important thing is to always keep in mind that we are not only looking for the diagnosis, but for enough material to offer our patients all of these types of novel therapies. Without enough tissue, we will not be able to offer our patients the best therapies available that we have right now.The landscape of the treatment of lung cancer has completely changed recently. This is due to the approval of pembrolizumab in the frontline setting versus chemotherapy in those patients who have more than 50% levels of PD-L1 expression on their tumor. That approval by the FDA recognized the superiority of pembrolizumab over several chemotherapy regimens for both histologies: adenocarcinoma and squamous cell carcinoma.

Now, when I have a patient with stage IV lung cancer in my clinic, it is very gratifying that I can talk to them about targeted therapy, chemotherapy, and also immunotherapy. Right now, at the end of 2016, we are able to expand the options for our patients with good results in terms of efficacy but, importantly, options with low toxicity profiles.

What challenges are researchers still facing?

That’s the most important thing for me, as a thoracic oncologist, to have that opportunity to help many patients with lung cancer and limit chemotherapy. It will still play an important role, but perhaps our patients will have something much better in the first line of treatment.We need to continue working very strong to identify more pathways that we can target. We have EGFR, ROS1, and ALK as genomic alterations for which we have targeted therapies. However, there are more. There are others such as HER2, RET, MET, and BRAF that we could potentially have targeted therapies for. They are not approved yet for first-line treatment, but when a patient has those genomic alterations, we can use it in the second-line setting. We hope that those kinds of alterations or pathways make it to the first-line setting in the near future.

Also, unfortunately, 30% of patients with lung cancer carry out the KRAS mutation and we have still not found a target that shows great efficacy against that big number of patients with that mutation. More research needs to be done in that direction.

What else is important to mention in lung cancer right now?

Of course, we need to continue making progress with immunotherapy. We have seen it with single-agent immunotherapy, but what about in combination? The PD-L1 pathway or the checkpoint inhibitors is only 1 piece of immunotherapy. Now, we need to understand how to better stimulate the immune system and how to attack the cancer cells. However, if we can combine that with other pathways in the immune system and make that effect more powerful while also keeping the toxicities low, that will be great for patients—not only in lung cancer, but cancer in general.In general, I want to emphasize the importance of clinical research—the importance of participating in something that may change the life of many other people who are affected with cancer. When I meet a new patient, I will tell them about clinical trials and try to explain to them how they can expand their options. The standard of care will be there. Of course, you have a good clinical trial when the patient can receive the standard of care plus something else. That is the best clinical trial we can develop. I encourage everyone to continue supporting research in cancer.