Treatment Options for NSCLC: A Discussion on Coverage, Clinical Outcomes, and Payer Perspectives

Featuring Martin Dietrich, MD, PhD, Medical Oncologist, US Oncology Network 

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Dr Dietrich: Hello, I'm Dr Martin Dietrich. I'm a medical oncologist with the US Oncology Network in Orlando, Florida. I practice mainly thoracic oncology. I'm a geneticist by training, so those two specialties overlap. And I'm excited to be here. Thank you so much for having me.

For patients with NSCLC, what treatment options are available on the market that you’re aware of that are covered by insurers?

Dr Dietrich: Well, we have a broad range of treatment options. Obviously, chemotherapy is always a backbone for both treatment options combined with immunotherapy and also, more recently, also with targeted therapy. So chemotherapy is sort of the mainstay of traditional drugs. And we've developed into refining our immunotherapies, both as single agents and as combinations. I think that's an opportunity for some of the non-small cell lung cancer subtypes, as well as targeted therapies. We have at least 10 molecular markers that are defining molecular subtypes. And they're all treated differently. They all have different drugs. So there are dozens of different therapies available for non-small cell lung cancer, understanding that lung cancer is a very heterogenous family of diseases that we’re treating. 

There appears to be a gap in EGFR treatments available for patients with NSCLC on most health plans. What clinical outcomes could help payers provide coverage for this treatment regimen? 

Dr Dietrich: So non-small cell lung cancer had its first discovery in the genetic definition of non-small cell lung cancer with the epidermal growth factor receptor, or EGFR, discovery in the early 2000s. It was very clear that this is a subset that responds very well to targeted therapy compared to the chemotherapies that we've had. We've had options that were pill-based and were able to induce responses in metastatic, non-small cell lung cancer patients where we didn't see responses before. They've evolved. We have first, second, and now third generation drugs that have been approved. Two third generation drugs are in the market now. Those are the ones that we predominantly use in the metastatic space. 

The problem with genetic suppression of cancer is that eventually the cancer grows resistant and is able to progress despite targeted therapy because it genetically evolves. So it's an expected process. And depending on the subtype of EGFR. EGFR is not one mutation, but also a very broad family of mutations. We do see higher and lower risk subtypes. Some of them are defined clinically. We see disease that is confined to the chest. But sometimes we also see disease that's widely metastatic, including the brain, which we would define as clinical high risk. And there's some molecular high risk features for patients that have secondary mutations, that may have a mutational type as the primary driver that may be more aggressive at Exon 21. And those actually have a significantly reduced prognosis both in the EGFR spectrum of expectations. And for those, you’re really thinking about additional strategies to up-front determine the prognosis and need for potential treatment escalation. And for those, the combinations have been very helpful. So we want to extend the usefulness of these third generation TKIs in the first line setting and we do have, again, 2 options now in the first line setting to do so. 

A new study was released for a 1L therapy using amivantamab plus lazeritinib in patients with previously untreated EGFR-mutated advanced NSCLC. According to the study, progression-free survival was significantly longer in patients who used this treatment compared to the current standard of care. With these study results in mind, what will payers consider when trying to determine coverage for this drug regimen? Would this drug regimen be a more viable option? 

Dr Dietrich: The combination of amivantamab as a bispecific antibody, the first bispecific antibody in solid-tumor oncology, and lazeritinib is a new combination. There has been some experience with amivantamab for rare EGFR mutations in Exon 20, and previously also for patients that have progressed on first-line treatment of the EGFR. But always with lung cancer, we try to give our best therapies first. And here we evaluated a combination of lazeritinib, a third-generation EGFR TKI, with amivantamab as an antibody that targets EGFR from a different angle, but also targeting EGFR, plus the c-Met receptor which is one of the main mechanisms of resistance in EGFR-driven non-small lung cancer, and thereby producing longer and more durable responses in subsets of lung cancer. I believe we are looking at a progression-free survival benefit that transcends across all subgroups, but it's particularly pronounced in those subtypes that I mentioned previously are more challenging, both clinically and molecularly in terms of their treatment responses. So it is an intensification of treatment. It's certainly more involved than the pills that we used previously. But they also have advantages with regards to efficacy and duration of usefulness in the clinic.

I think it's important when we see an EGFR patient in the clinic to really understand all the nuances of treatment. Again, this involves that clinical assessment, including a radiographic assessment with a PET scan and MRI. As well as understanding molecular features. And again, this is no longer a binary call of EGFR mutation positive or negative, this is much more grey zone now. So, for us, much more understandable that puts prognostic and predictive nature of these mutations. And finding the right treatment for the right patient has gotten really much more complex, but it's exciting to see that we have more options, options that provide more lasting responses compared to our previous standard of care alone. So we're excited to have these options in clinic and to be discussing them with patients when they get unfortunately diagnosed with these very aggressive and metastatic subtypes of lung cancer.