Spigel Applauds Latest Advances to the Treatment Paradigm During Lung Cancer Awareness Month

David Spigel, MD

The typical prognosis for patients with lung cancer was particularly dismal years ago, but the development of immunotherapy and targeted therapy advances have reenergized this field, which is now considered one of the most exciting fields in oncology today.

The excitement of immunotherapy and targeted therapies is not lost in other cancer types, but these new therapeutic approaches have been able to drastically improve outcomes in patients with lung cancer. The benefits observed with these treatments have also demonstrated the value of testing patients as many mutations and alterations can be found in lung cancer that can be targeted with some of these novel therapeutic approaches.

Some of these alterations that can be detected and targeted in treatment include EGFR, ALK, BRAF, ROS, and RET. Additionally, KRAS and HER2 are becoming important targets in this space, and this doesn’t begin to touch on other things that can be detected with these genomic tests, such as microsatellite instability (MSI) or tumor mutational burden (TMB).

In an interview with Targeted Oncology during Lung Cancer Awareness Month, David Spigel, MD, chief scientific officer at Sarah Cannon Research Institute, shared his insights on the evolving treatment paradigm in lung cancer and how the latest advances have impacted his treatment decisions for patients with lung cancer.

TARGETED ONCOLOGY: Do you first want to discuss some of these advances and how you've seen them evolve?

Spigel: The 2 biggest areas of kind of excitement and advance have been in kind of targeted therapies and in immunotherapy. This is not just lung cancer, but more so all of oncology, but lung cancer, to me, is the example of where that excitement has been.

In targeted therapies, there's been huge advances in technology for sequencing. In my clinic and as part of research, this has been a huge advancement in how we test on the profile. Then what can we do once we find targets has been exciting because for a long time, we had a few targets, EGFR and ALK, but now we've added many to that list. [Specifically], we have ROS, we have BRAF, and we have MET exon 14. Soon we're expecting KRAS, and HER2 is around the corner. I've left out RETalready, which we have approvals in for 2 agents. We have TRK, we have MSI, we have high TMB, and we have PD-L1. We have a lot of biomarkers that we can use to assess how to find a targeted approach for patients that benefit.

Flipping that around, we have immunotherapy where I mentioned a couple of potential biomarkers, such as TMB, MSI, and PD-L1, but there is just a huge kind of array of options in first-line setting of lung cancer treatment. Actually in non–small cell lung cancer, we have advances in stage 3 disease with immunotherapy, and so it's hard to find a place where targeted therapy and immunotherapy aren't a part of an oncologist's daily conversation with a new patient with lung cancer, whether it's small cell or non-small cell.

TARGETED ONCOLOGY: Could you elaborate on some of the common targets we see in lung cancer and the different treatment options for these patients?

Spigel: In terms of the way I approach non–small cell lung cancer treatment, I always consider that there could be a target, and we don't know that because of the patient's history or just looking at them. We have guidance out there that tells us if they have advanced disease, and it's adenocarcinoma, you should broadly sequence them, and I agree with that. However, I think that applies to our patients with squamous cancers as well, and I don't let smoking history interfere with my decision to comprehensively test patients because you can find a lot of different markers.

Broad testing, I believe, is standard of care in any patient with advanced squamous or non-squamous lung cancer, and I do it in small cell as well. Now, if you have access to research, I think it makes a lot more sense for things like small cell where you can steer patients to potential trials. However, I'll be the first to admit, in small cell, that testing doesn't help me make a decision on how to care for those patients, and so for those patients, I'm thinking about it from a research standpoint. I think for non-squamous and squamous lung cancer, there are opportunities that can arise.

TARGETED ONCOLOGY: At this time, do you think testing is being done enough for these patients, or is there still a need to improve on testing methods in the clinic?

Spigel: In oncology, in general, we probably could do a better job just testing more patients. We see this in our own network, where we have some areas where testing is very common, very standard, and in some places, not so much. I think the technology is confusing, and we were kind of always taught in medical school not to order a test unless you know what to do with the results. Sometimes it can be overwhelming to not know what to do with the results. I also appreciate that a lot of these things are not common, and so you test you test, you test, you don't find anything, you feel like that's pretty useless. It's not changing your decision. It's just when you find 1, if you have 1 patient where you find ALK, ROS, RET, it motivates you to keep looking and finding.

I think we could do a better job, but I think 1 technology advancement that will help is when we get to a place where you can do 1-stop shopping, so-to-speak. One test that covers everything, or all the things you need, and it comes back fast. It's easy to get, and so we're kind of there; tissue can find a lot of things, and you can do even immunohistochemistry testing on tissue while you're doing next-generation sequencing testing. The turnaround can be now anywhere from 14 to 21 days. Plasma is easy, and it takes about 5 to 10 days to get a result. You can find even these days TMB and hundreds of potential generic alterations. Plasma is not perfect, it's not the most sensitive test, it's very specific and not the most sensitive, which means when you don't find something, it doesn't mean that something couldn't be there.

I think as those technologies get better and faster and easier, hopefully cheaper, and the turnaround time becomes shorter, we'll all be doing it routinely in all advanced cancer settings. It's my belief.

TARGETED ONCOLOGY: How do you see the field evolving in the coming years?

Spigel: For the last 8 years, it's hard to believe that there are so many promising directions to go with, as we've mentioned in the targeted space and immunotherapy space, but leaving out a lot of other areas that classically are important pathways in drug development, so DNA repair is looking very exciting. We've seen that in breast and ovarian cancer and pancreatic cancer. I think that there's other important biology besides immunotherapy and targeted approaches that can be exploited in lung cancer treatment, and literally hundreds of drugs in development.

I'm excited because I think we can all feel rest-assured, in the next 5 years, that there's going to be other targets that are discovered, other drugs developed. We're going to get better at pairing drugs, understanding mixed drugs together. I think we're going to probably come closer to solving this dilemma of should immunotherapy ever be used in a patient with a targeted driver? And if so, when and how to combine or sequence that therapy?

These other non-targeted non-immunotherapy approaches still play a role for traditional cytotoxic approaches, the antibody-drug conjugates look very exciting, bispecific antibodies, which still employee an immune strategy, so I think those look very promising. Immune effector cell therapy, maybe not CAR T per se, but in the effector cell therapy, delivering T cells into patients with solid tumors, I think remains something to be excited about.

I tell folks, this all the time: I don't think there's a more exciting time to not just be a lung cancer researcher, but to be an oncologist. I would add to it to be a doctor, there's so much good things that we can do now that we just didn't even imagine we could do 15 to 20 years ago. We don't have to wait a decade for these things to mature, and we can see changes in our field in a year. That's fantastic, and it's an exciting time for researchers, for clinicians, hopefully, as well for our patients and their families.

TARGETED ONCOLOGY: What message would you like to share for Lung Cancer Awareness Month with your colleagues and peers in the field?

Spigel: This past June, we saw an amazing number of drugs approved by the FDA. All of that happens because of research. We have to test these drugs to get them out there, and so we have so many opportunities now to give a patient something outside of a study. I'm the first to admit that I got a RET inhibitor for a patient off study or outside of a study setting 2 weeks ago because I couldn't get them on a study, but research is more relevant now maybe than ever because we have opportunities to take advantage of this momentum to build upon this.

We've got a lot of work to do, and in the busy world that we live in, a strange world right now, the number of opportunities off-study to pick up the phone and get a drug available that maybe you couldn't get at 1 point is easier than it's ever been. That's great, but research continues to be pivotal, and without your help and interest, and engagement with patients, it gets harder to do. I appreciate everybody's help and trying to kind of work together to find the next best there.