New Therapeutic Options Can Prolong Survival in Patients with Mutated Non-Small Cell Lung Cancer


Historically, there are many hard-to-treat mutations of non-small cell lung cancer.

Whitney E. Lewis, PharmD, BCOP, a clinical pharmacy specialist at the University of Texas MD Anderson Cancer Center, Houston, Texas, discusses novel therapeutics for patients with non-small cell lung cancer (NSCLC), health literacy, interpreting clinical data to understand toxicity risk, and much more about NSCLC with Pharmacy Times for our live coverage of the Hematology/Oncology Pharmacy Association (HOPA) Annual Conference 2023, Phoenix, Arizona, March 29 to April 1, 2023.

PT Staff: Could you discuss some recent clinical trials and how outcomes have impacted the NSCLC treatment landscape?

Whitney E. Lewis, PharmD, BCOP: It's been really exciting to be in the lung cancer clinic for the last several years. I like to tell my residents that we don’t treat any type of lung cancer the same as we do when I started about 8 years ago. So we've had a lot of great breakthrough discoveries in both the adjuvant setting for early-stage patients as well as in the metastatic setting.

So, before we used to just give adjuvant chemotherapy after patients would have surgery, we now have 2 indications for checkpoint inhibitors for patients who have received a curative resection. We also have adjuvant Osimertinib (TAGRISSO®; AstraZeneca) for patients with estimated glomerular filtration rate (eGFR) mutations who've had a curative resection from the Adaura trial. So, PEARLS/KEYNOTE-091 and IMpower010 trial and Adaura have completely reshaped the landscape for patients that are curable in terms of a surgical reset resection. And we also (it's not necessarily new data) but we also have a 5-year overall survival (OS) update for patients that received adjuvant durvalumab for patients who got concurrent chemotherapy radiation.

In addition to patients that got a surgical resetting resection. We also have the PACIFIC study that has now a 5-year overall survival update for patients that can also get adjuvant immunotherapy for a year after curative intent, chemotherapy radiation. And for the metastatic setting, we have brand new checkpoint inhibitor indications. So, we now have from the POSEIDON regimen, we have durvalumab and tremelimumab in combination with chemotherapy. So that's really exciting for us because they looked specifically at a couple of subgroups that were more traditionally considered hard to treat. So, patients that have STK11, and K1 mutation. And those patients had a great response.

And it's again, kind of considered more difficult to treat mutation, so that's been great for those patients. We have new chemotherapy, checkpoint inhibitor combinations, and, very exciting, we have some new tyrosine kinase ihibitor (TKIs) for patients that have Kirsten rat sarcoma viral oncogene homolog (K-RAS) G12C mutations, which is actually one of the most common mutations in NSCLC but has historically been considered a mutation that's more prognostic than therapeutic. And now we have drugs that have good response rates that can be used after patients fail chemo-immunotherapy and prolong survival. So that's a huge win for the non-small cell landscape.

PT Staff: What factors in clinical practice limit the number of patients with NSCLC who are eligible for early-stage clinical trials? (How does this impact outcomes?)

Whitney E. Lewis, PharmD, BCOP: So I don't know that I think it impacts patient clinical outcomes. But you know, we're a referral center. So we get a lot of patients from the community who want to come for a second opinion, and don't necessarily have the means to stay in a foreign city for several weeks or even months, depending on what the recommended treatment would be. There's not as much funding for patients that have NSCLC as there are for other types of cancers, we don't necessarily have our own foundation that provides a lot of financial support. So I do think that that is a factor.

Occasionally health literacy can be a factor. And for some of our early-stage patients, occasionally, they're quite young and still working. So it's not necessarily a population of only retired people who don't have other obligations, to make work on their normal schedule as well. So additionally, a lot of these patients are older, so they may not fit the criteria for a clinical trial in terms of performance status, if they're experiencing a lot of symptoms from their cancer, their baseline kidney or renal function may not be up to par for what we would consider an ideal clinical trial candidate. So I think there's actually a lot of factors that go into that, as well as many patients just see their community doctor, and don't think to go to a big Cancer Center and think that they may have additional options if they were to pursue that.

PT Staff: How can patients become more informed about clinical trials and eligibility factors?

Whitney E. Lewis, PharmD, BCOP: I think a lot of patients, you know, it, it's still a generation of I do what the doctor tells me they're not necessarily googling everything. So I think some of it may just be, you know, they're not aware that there could potentially be options. Even just talking to my mom last week, she was under the impression that clinical trials are just for people that have no other options, not necessarily something early stage that we're trying to change that treatment landscape and create more options. So I think there's maybe a little bit of a an understanding gap for patients in the community as well.

PT Staff: How are pharmacists able to predict the toxicity profile of different adjuvant and neoadjuvant monotherapies? How can this help prevent/maintain drug toxicities?

Whitney E. Lewis, PharmD, BCOP: I think clinical pharmacists do play a crucial role. We really are considered the drug experts on the team. So you know, when I'm talking to my physicians about what the treatment plan is for this patient, we do a lot— we're looking at what the patient's comorbidities are, what their other medications are, we want to look at their kidney liver functions. So, you know, we kind of look at all of that as well as the patient as a whole, such as “what's their performance status?” And we're intimately familiar with clinical trials. So of course, we're reading them just like the physicians are, but with a slightly different scope. So we want to look and see like, “Okay, well, what was the percentage of, of this toxicity? And how many patients had a high-grade toxicity? And what can we do proactively to try to help prevent that? Which patients may be at more risk for that?”

I think we don't necessarily predict it, but we do look at the clinical trial and try to interpret that based on what we know about the patient and try to integrate that information and kind of see like who may be at a higher risk for what we try to look at all of our patients is individuals and not necessarily a cookie cutter approach. You know, everybody is a little bit different. Everybody has slightly different medications they may be on or comorbidities or other things that they're just anxious about and you know, even just patient anxiety can sometimes help manifests some toxicities, for example, like gastrointestinal (GI) upset nausea. So a lot of that individualized patient teaching and trying to reassure them and comfort them can be really helpful too.

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