With the Rapid Expansion of NSCLC Therapy Options, Pharmacists Take an Advanced Role on the Care Team

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Whitney Lewis, PharmD, BCOP, discusses how the treatment armamentarium for NSCLC has expanded in recent years and the associated cause for this acceleration.

Pharmacy Times interviewed Whitney Lewis, PharmD, BCOP, director of pharmacy cancer care at Mayo Clinic, on her presentation at the Hematology/Oncology Pharmacy Association (HOPA) Annual Conference 2024 in Tampa, Florida titled “What’s New in NSCLC Therapies? Key Takeaways for Your Pharmacy Practice.” Lewis discusses how the treatment armamentarium for non-small cell lung cancer has expanded in recent years and the associated cause for this acceleration in treatment development.

Pharmacy Times: How has the treatment armamentarium for non-small cell lung cancer (NSCLC) expanded in recent years, and what do you think may be accelerating this expansion?

Whitney Lewis, PharmD, BCOP: I started in lung cancer about 9 years ago, and I always joke to my residents that we don't treat any type of lung cancer—like literally any type—the same now as we did back then. So, I think what we've been really fortunate in that we have finally started to find treatments that are making an impact on our patient population. I think there's a lot of research going into drugs and development, and I think we're really starting to see the benefits of that and we are the beneficiaries of that. So, I think from our patients’ standpoint, we're starting to do widespread molecular profiling. We're a research institute, so almost all of our patients are getting genetic testing on their tumors. So, we're starting to see interesting patterns, we're starting to think about hypothesis-generated questions like, ‘Oh, what might be the reason this population is responding to this or not responding to that.’ And I think with the number of drugs that we've had approved in recent years, be that targeted therapies immunotherapies, we've had antibody drug conjugates, there's been all sorts of great drug development, and I think we’re starting to actually see this help patients, which is also fueling that passion with our partners, the pharmaceutical industry, and patient advocacy groups. So I think it's just a little bit of everything. I think, once you get that spark, we're kind of starting to see the fire.

Image Credit: © catalin - stock.adobe.com

Image Credit: © catalin - stock.adobe.com

Pharmacy Times: What is the role of immune checkpoint inhibitors in NSCLC treatment today, and has this changed in recent years?

Lewis: When I started about 9 years ago, immunotherapy was on clinical trial. And I remember asking my preceptor, ‘Hey, this doesn't seem to work. Why are we studying this?’ And I just hadn't been in the clinic long enough to see the patients that were truly benefiting from these therapies. So yeah, from when I started, it was a second-line option being compared to docetaxel. And now we give immunotherapy upfront to almost every patient unless there's a strong contraindication: Have they had a solid organ transplant? Are there other severe autoimmune issues? Do they have a driver mutation where we should be targeting that instead? But, from our perspective, everyone should be trialed with immunotherapy, so we don't have enough data yet to say which patients are definitively not going to respond. So we always try to give the benefit of the doubt because it's really our patients’ best chance to have a durable long-term response and the toxicity profile for most patients is very tolerable. So, the risk benefit absolutely favors treating patients with immunotherapy.

Pharmacy Times: What are some of the advancements in targeted therapies in recent years?

Lewis: We've had several new drugs approved and some of those drugs maybe aren't brand new, but we also have new indications. For example, lorlatinib [Lorbrena; Pfizer] has sort of moved from second-line ALK to frontline ALK as an option, we just had repotrectinib [Augtyro; Bristol Myers Squibb] approved frontline for ROS1 fusions. We've had trastuzumab deruxtecan [Enhertu; Daiichi Sankyo] FDA approved for HER2, we've had KRAS inhibitors, we've had NTRK inhibitors. So honestly, the number of drugs that we're getting to target specific mutations is starting to just really stack up, it's becoming a little bit hard to keep on top of, which is such a good problem to have. Honestly, we're very excited about that.

There's also new drugs being developed. We're starting to combine current drugs that we've already used with other types of treatments to try to pick our best shot on goal for our first-line therapies. So I think there's a ton of drugs that have been approved, but I would say, kind of notably, we're starting to see drugs that maybe we used more reserved moving up to the frontline setting. And then we also have novel drug approvals, for example, like the repotrectinib for ROS1.

Pharmacy Times: What are some novel therapeutic targets that are getting attention in clinical research recently?

Lewis: One of our most exciting approvals has been looking at patients that have exon 20 insertion mutation. So that's kind of in like the pack domain of EGFR. So historically, we've always sort of had some steric hindrance because of the change in the conformation to the binding site to that EGFR. And now we historically had 2 drugs approved for that, mobocertinib [Exkivity; Takeda] which is unfortunately undergoing an FDA withdrawal, but also amivantamab [Rybrevant; Johnson & Johnson], which is very exciting for this patient population that historically we know that we should be able to target it, but we really haven't been able to do that. So, I think that's kind of been one of our most exciting FDA approvals has been amivantamab first in the second line setting and now moving it up to frontline in combination with chemotherapy and really kind of getting a strong benefit there, and then also expanding that because it is a bispecific molecule and knowing that that may also help benefit some of our patients that may have a more classical sensitizing EGFR mutations. One of the most common mechanisms of resistance to EGFR is actually MET [mesenchymal epithelial transition] amplification. And so since amivantamab binds to both of those, it's actually a very logical leap to go to once patients have potentially progressed on osimertinib and express that MET amplification. So that's been exciting, and then we're also looking at that in the second line with chemotherapy and in the frontline with chemotherapy and a TKI. So I think that's been one of our most exciting molecularly driven things.

We're also looking at HER3 with patritumab deruxtecan [HER3-DXd; Daiichi Sankyo]. So that'll be really exciting to see. It's preclinically looking very good. It'll be nice to see when the final data reads out, but [it may be] another option for third-line for patients that have EGFR mutation. So, I think right now, they're kind of getting a lot of attention. But there's also other ALK inhibitors that are being studied, other ROS1 [directed therapies]. So, it's, it's a great time, if you have lung cancer, and you have a mutation, there's a lot of drugs undergoing development right now that may potentially benefit.

Pharmacy Times: How might clinical research in the field of NSCLC be impacted by the push to advance health equity and inclusion in clinical trials in recent years?

Lewis: That's a great question. We are a referral center, so we do see patients with a wide array of socioeconomic backgrounds. I always say, we see some of the poorest patients in Houston, and the richest patients in the world. And we're very lucky in Houston that it is a very multicultural area, that's not necessarily the case everywhere. So I would hope that that would mean that, with a push towards having more diversity, equity inclusion, that there will be more grants for some of these patients who may have difficulty traveling to larger centers, and really start to have that population that we at least see in clinical practice, again, being a very diverse population in general where I work, and start to see clinical trials that reflect that in practice.

On the other hand, you also want to make sure that you're not delaying patients getting enrolled on clinical trials, waiting for some of that, too. So, I'm hoping that it'll be a very positive thing. I think it's something that's very important for our patients. We've had occasional patients expressed that there's not really very many patients like me on this trial, are you sure it's going to work for me? And that's a very good question. Because we can't tell you 100% for sure there's nothing that would suggest that it would be less efficacious, but we'd love to have that data to tell you in practice. But on the other hand, we also want these drugs out as quickly as possible with that data. So, you also want to try to push to get as much accrual as possible as quickly as possible to.

Pharmacy Times: What are some areas you would recommend pharmacists focus education among care teams and patients on NSCLC treatment expansion?

Lewis: I think that's a great question. One of the areas that I spend a lot of time in my clinic—and I have clinic 5 days a week, a lot of my providers might only have clinic one day a week, and otherwise, they're very focused on their research and their other academic responsibilities. I spend a lot of my time helping manage the patients with toxicities, rather than simply trying to educate the providers on what some of the toxicities are, which I do think is very important, because they're the ones that are kind of floating the idea of the drug to the patient first. So obviously, we want them to be very well informed about what that toxicity profile looks like. I think also just establishing yourself as the go-to resource to help them manage those toxicities is one of the best ways that we can try to be involved and more integrated in those multidisciplinary teams. Yes, we certainly want to educate, but we also want to make sure that we are available as a resource to really also help because no one will ever be able to match our knowledge of drug-drug interactions, dose adjustments for organ dysfunction, and things like that. But with all of the new targeted therapies, a lot of these have very unique side effects that we're not necessarily used to thinking about or having to manage. We're also seeing some younger patients. So kind of reminding the physicians to, ‘Hey, have you talked to this patient about fertility preservation, for example,’ and just kind of trying to help fill in that gap with a different perspective that that we all bring to the table between our MDs, APPs, the pharmacists, just kind of trying to focus on that drug knowledge, toxicities, acquisition of the drug, sometimes we're helping provide forms or making sure that people get connected in the right way to help with drug company assistance for patients that may not be able to afford their medications can be really helpful too.

So honestly, we wear a lot of hats. It's a little bit hard to narrow down. But I would say if I had to pick my top 3, we want to do provider counseling on some of these toxicities. Also, what are the approvals of the drug and exactly how are we allowed to use them because that can get a little bit muddied sometimes too. And then just kind of helping manage some of the drug-drug interactions.

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