Advancing NSCLC Care: Targeted Strategies, Real-World Barriers, and the Future of Treatment Pathways

Dr. Rajat Thawani, a thoracic oncologist at OHSU Knight Cancer Institute, discusses groundbreaking advances in lung cancer treatment—highlighting the promise of antibody-drug conjugates (ADCs), the critical role of biomarker testing, and the nuanced challenges clinicians face in delivering timely, individualized, and guideline-aligned care amid a rapidly evolving therapeutic landscape.

Rajat Thawani, MD: I am Dr Rajat Thawani. I am a thoracic oncologist at OHSU Knight Cancer Institute in Portland, Oregon. I treat lung cancer, and I also do phase 1 clinical trials.

From your perspective, what are the most significant recent innovations in the treatment landscape for non-small cell lung cancer (NSCLC)?

Dr Thawani: That's a very loaded question. There's a lot happening in lung cancer. It ranges from targeted therapies to immunotherapies, to antibody-drug conjugates (ADCs), and I think all 3 of them individually are developing at a rapid pace. What we're seeing more and more of in lung cancer is development of ADCs.

It's a targeted way of giving chemotherapy, where a chemotherapy is attached to an antibody, and the antibody deposits on the cancer or it gets attracted to certain proteins that are expressed on the cancer. It's able to deposit that chemotherapy to the cancer cell in a more concentrated and targeted fashion. That way we're able to give higher doses of chemotherapy that we weren't able to give before.

There are different kinds of targets that are being approached to target this ADC. We're testing them in different kinds of lung cancer and different kinds of patients. There's a lot of research in this space that is exciting, that we recently saw at ASCO last month.

What are the major real-world challenges clinicians face in getting patients timely access to biomarker testing and targeted therapies?

Dr Thawani: That's a really important question. We have moved to relying on biomarkers significantly in lung cancer. For example, once a patient gets diagnosed with lung cancer, we truly have to wait for next-generation sequencing (NGS) testing and PD-L1 testing to make decisions on what treatment to offer to the patient.

One of the biggest barriers that clinicians face, but also that patients face, is waiting for the test to be done. For the test to be done, we need the tumor to go to a lab that can extract DNA, and sometimes RNA, and get biomarker testing done. That can take a couple of weeks.

Waiting for that biomarker test to be complete and then using that biomarker test to offer targeted therapy to patients takes time. That is probably one of the biggest challenges. If you can imagine, from a patient's perspective, they know that they have cancer and they're not able to start treatment while waiting for the test. For physicians, we send these tumors out for testing and sometimes there’s not enough for DNA extraction or they fail to report a result. Those challenges are real and can affect patient care.

We have some alternatives with liquid biopsies that are getting better and faster. It's getting better, but tissue is always an issue. It truly remains one of the major challenges. At this point, most people who treat lung cancer frequently know that they have to wait for biomarker testing. We're getting better there, but we'll still have to wait for that NGS.

What are the most significant considerations when integrating immunotherapy into treatment plans for patients with oncogenic driver mutations?

Dr Thawani: That's also a very interesting question. If you think about most oncogenes, these patients do not end up getting immunotherapy as a standard-of-care option right now. If you think of EGFR, ALK, ROS1, NTRK, and a lot of others, most of these patients do not get immunotherapy because immunotherapy does not work. That is probably the most significant consideration for this group of patients.

Now, there are certain other oncogenes, like MET exon 14 skipping mutations and BRAF V600E mutations where immunotherapy may be useful in a certain subset of patients. We still haven't clearly established which patients should and should not get immunotherapy out of this subgroup of patients with oncogenes, but more and more we're going toward targeted therapies first because targeted therapies work. We're leaving intravenous (IV) treatments like chemotherapy and immunotherapy for later, but that's not universal. There are many reasons why a lot of patients cannot get targeted therapy because of comorbidities or potential side effects.

I would say that what oncogene comes up in the NGS report is probably the most significant consideration for immunotherapy. Most of the oncogenes seen in people who have not smoked in the past and develop lung cancer are less likely to respond to immunotherapy. On the other hand, some of these oncogenes can be seen in patients who have smoked in the past, and there I would say immunotherapy probably still has a role. This is an area that is still being explored, to be determined.

How can payers and providers collaborate to ensure patients receive the most appropriate targeted therapy without unnecessary financial burden or access delays?

Dr Thawani: The barriers that payers and providers have for a collaboration are that payers don't have enough information on why we're using a certain test. There are often delays in trying to get the most appropriate targeted therapy for these patients, and we don't want to wait. We already wait for biomarker testing; if we have to wait longer for therapies, it just adds more time until treatment can actually begin. Sometimes patients might have to pay out of pocket until the issues get resolved.

Having clear guidance on what targeted therapies are supposed to be offered to patients, following those guidelines, and having good criteria on why physicians are offering certain therapies to patients to decrease the prior authorizations that physicians struggle with [is important]. I'm sure that if you ask a payer—and I don't know their perspective totally—they probably have certain things that we could do better. The easiest thing would be for us to sit down and discuss what the barriers are on both our sides and try to navigate them.

Right now, from a purely physician standpoint, there are delays in prior authorizations or getting approval for drugs that the patient needs. Maybe we're not describing in detail in our notes why we're offering a drug; maybe that's the reason, and we can be better at that, but right now time is crucial for most of these patients. It's not just the disease, but you can imagine the anxiety of sitting on a diagnosis and not getting treatment.

How are clinicians balancing guideline-based care with real-world complexities such as comorbidities, performance status, and social determinants of health?

Dr Thawani: That's a very complex question. Most guidelines do not include real-world problems and complexities like comorbidities and performance status and patients' social determinant of health. It's hard to include them because it's just so complex.

What we strive to do is know more about our patients and know more about the drugs that we are offering them so that we're able to navigate if the patients are going to be able to tolerate the drug, if they're going to be able to stay on the drug for long enough, what barriers they might face on the drug, or, if there are multiple options, which drug they're probably going to be able to rely on or be compliant with or be able to take regularly.

A lot of times, we have to choose between an IV drug or an oral drug. Some patients might prefer oral drugs so that they don't have to come in, and their barrier might be transport. Some patients might forget to take drugs and have no transportation barrier. For them, an IV treatment might make more sense.

There are a lot of different aspects that are too real and too hard to incorporate in guidelines. This is why having an experienced physician or oncologist who's working with you is helpful, who understands the barriers that patients face but also knows the drugs and the potential side effects and tries to match expectations and real-world scenarios with your care.

With increasing complexity in the NSCLC treatment landscape, how are providers adapting treatment pathways to reflect new approvals and real-world factors?

Dr Thawani: Lung cancer is getting harder and harder to treat, which is why people like me have a job. We're only focusing on 1 or 2 diseases. We had an approval yesterday for a drug, and these approvals keep coming and making the treatment landscape more and more complicated. When I say complicated, it's actually a good thing because patients have more options and they're living longer than they did maybe a decade ago.

We have guidelines that we follow, and those guidelines are pretty quickly updated with approvals and data that come through. At the same time, even if you want to do a one-time second opinion with someone who's an expert in this disease category that you might have, I think it makes sense because they're more up to date with the data, they have more knowledge about the potential side effects, and it's probably worth a one-time discussion, whether it's in person or virtually.

Physicians and oncologists truly are trying to keep up with the literature, but it's changing so quickly that just having an expert in lung cancer be available to you is definitely helpful. We work with our community oncologists very closely, who we have a lot of respect for because they see all different kinds of cancer. They're closer to the community, they see a lot more patients, and they're serving a lot more patients pretty close to where they are rather than academic oncologists who are separated out by distance or time from patients. Having a team that supports you through treatment is going to be crucial as this gets more and more complex.