Small Cell Lung Cancer Spotlight - Episode 17
Ryan Haumschild PharmD, MS, MBA, director of Pharmacy Services at Emory Healthcare and Winship Cancer Institute, spoke with AJMC® about health care resource utilization and clinical decision support in the care of patients with small cell lung cancer (SCLC).
Ryan Haumschild PharmD, MS, MBA, is director of Pharmacy Services at Emory Healthcare and Winship Cancer Institute, where he has wide range of clinical and management responsibilities for one of the nation’s largest academic integrated delivery networks. Winship is Georgia’s only NCI-Designated Comprehensive Cancer Center. Haumschild is a member of the editorial board for The American Journal of Managed Care® (AJMC®) and a board member for the Center for Biosimilars®. He spoke with AJMC® about health care resource utilization and clinical decision support in the care of patients with small cell lung cancer (SCLC).
This interview is lightly edited for clarity.
AJMC®:Let’s start by discussing health care resource utilization. What does it look like for a patient who is newly diagnosed with small cell lung cancer (SCLC), or one who is progressing into the treatment stage? Which areas of the health care system does the patient touch on a day-to-day basis?
Haumschild: Before a patient begins lung cancer treatment, they're going to review the pathology with a lung pathologist. This is critical, because small cell lung cancer responds well to chemotherapy, but it is not always treated surgically. We want to make sure it's not confused with non-small cell lung cancer, because the diseases involve 2 different, distinctive treatment strategies.
We'll also look at the immunohistory and examine the techniques for diagnosis and subclassification. Then, we're going to determine: does this patient have more limited disease, or extensive disease? And we talk about that because there are different therapy approaches based on whether the patient’s disease is limited or extensive. We know that patients with limited disease usually have immediate survival around 24 months and have higher 5-year survival rates around 14%. So, patients that have stage 1 or stage 2 newly diagnosed [SCLC] may be treated with surgery even though it's minimal, but often radiation therapy is something that's included as part of their treatment and health care utilization. Radiation therapy allows us to eradicate disease as much as possible. For those patients that don't wish to pursue surgery, radiation is another opportunity for us to reduce the size of the tumor burden.
We also want to complement that with chemotherapy. Typically, it's going to involve a platinum-based therapy or an etoposide. And currently, we're seeing base 3 drug regimens, such as utilizing 2 chemotherapies—we could use cisplatin or etoposide—combined with immunotherapy, such as atezolizumab or durvalumab. Those are typically the resources we see from an absolute treatment standpoint. We also see scans, and many of these patients who develop neutropenia, or any type of neuropathy will frequently visit the [emergency department]. And unfortunately, their 5-year survival isn't that strong yet, as we're still developing more medications. They will interact more often with an inpatient admission as part of their treatment regimen.
AJMC®:How do you evaluate the value of these treatments in SCLC, particularly when considering some of these new combinations? How do you evaluate the value of combinations with immune checkpoint inhibitors—atezolizumab or durvalumab—in the frontline setting? And then, there's also some newer agents in the second line, such as lurbinectedin. What is considered high value for these treatments?
Haumschild: Right now, high value is anything that's going to improve overall survival. Among current treatments for extensive-stage small cell lung cancer, we have carboplatin and etoposide plus a checkpoint inhibitor. And that's where we're seeing the triplet approach to therapy right now, with atezolizumab or durvalumab as the checkpoint inhibitors. There are a few studies out there that show some improved data. The IMpower study had patients with some of the similar characteristics that we've discussed with metastatic small cell lung cancer.1 And they were randomized either to carboplatin-etoposide, with or without atezolizumab, and what we saw there was that patients that have evidence of response after about 4 cycles were offered atezolizumab and maintenance therapy. What it confirmed it is that both the progression-free survival and the overall survival are superior in the patient population that received atezolizumab in conjunction with carboplatin and etoposide.
That’s really where we start to see that benefit to patients, both clinically and in terms of extending out any type of progression-free survival. When we talk about durvalumab, that’s another great option. Which brings us to studies such as the CASPIAN trial,2 that also utilized and reviewed patients with metastatic small cell lung cancer. That trial had 3 arms, but what investigators looked at most closely was the combination therapy of carboplatin-etoposide or nutritional chemotherapy with durvalumab, compared with patients without. And again, [investigators] found when patients had chemotherapy with durvalumab, it improved their overall survival, which I think is the cornerstone of what we're trying to do for those patients. So, that's really where we're starting to see the value—the addition of the checkpoint inhibitor.
You also mentioned second-line therapy. What do we do when someone relapses? For a while, topotecan was really the only evidence-based standard of care in second-line therapy. You could have used something like cyclophosphamide, doxorubicin and vincristine, or a platinum rechallenge. But that's really such an antiquated [approach,] and there were not really strong survival data. So, we’ve had a new therapy approved, lurbinectedin.3 It was granted orphan-drug status and it provided an objective response rate of around 35% which is really, really strong. And we saw that initially in a phase 2 trial and then that became confirmed in a phase 3 trial. And so lurbinectedin, to me, represents a potential new treatment for these patients with small cell lung cancer—but that’s especially true those with few options that have basically relapsed in treatment, or they've been exposed to chemotherapy in the front line setting and have failed or progressed.
We've seen some studies with [lurbinectedin] being utilized as a single agent; also, there are studies with a combination with doxorubicin or paclitaxel. But as a single agent, it's demonstrated a pretty strong clinical efficacy with that 35% overall response rate, and it improved the median duration of response at around 5 months, which is significantly better than topotecan, which was historically the second-line treatment.
AJMC®:When we talk about these therapies, what clinical and nonclinical considerations do you find to be of high value in small cell lung cancer? For example, what is a clinically significant increase in survival that you'd love to see in a new agent, or a safety profile that you'd like to see if something new came to market and the sponsors really hoped to make a splash in small cell lung cancer?
Haumschild: The good thing about small cell lung cancer is that there's opportunity for improvement in all those areas—and I think we're always trying to improve that journey for our patients.
We ask, what are the clinical and nonclinical outcomes? Let’s start with clinical: we leverage some of our real-world evidence or some of this additional data coming out of randomized controlled trials, so that we can improve overall survival. I think that's where the biggest opportunity exists. Also important is progression-free survival. We have several different therapies where we look at medium duration of response. How quickly can we see that duration of response to therapy? But to me, I guess the main thing that I think about a lot is the 5-year survival rate, it's still really low for small cell lung cancer patients. As we go through the journey and talk to patients, that's something they recognize can sometimes be less motivating because they know that even going through chemotherapy, even with this innovation of PD-L1 or these new cytotoxic agents, we still have opportunity for improvement.
I think those clinical outcomes are going to drive therapy, but while we're getting there and the way we keep patients on therapy I think is managing the side effect profile. When we look at some of these patients, you want to reduce the amount of abandonment rates. So even though we may not have high 5-year survival rates, how do we reduce abandonment rates—and that's really focusing on the treatment toxicities. When we look at some of these medications, even with the immunotherapies, we think of ototoxicity and neuropathy that are frequently seen with patients, that will cause them to abandon therapy. Or when we think about newer agents in the second-line setting like lurbinectedin, you also want to decrease the amount of neutropenia. So, I think early on, supportive care therapy is going to be important. Improving patient-reported outcomes—because we know those are tied heavily to adherence—and their motivation [to stay on] therapy will create a huge improvement.
The last item, and one of the most important ones, is reducing the amount of financial toxicity. It’s great that we're adding more therapies but if we think about traditionally in small cell lung cancer, there was an immunotherapy. So now as we have triple therapies, patients must come on-site, which requires transportation, it requires monitoring, it requires premedications, and potentially growth factors that are being proposed to them. How do we make sure patients can afford these types of therapies? And I think more we can leverage patient assistance programs, utilizing medication assistance but not just for medication but also coordination and supportive care. I think that's what ultimately is going to support patients and then eventually reduce total cost of care. Because if patients are staying adherent, we're minimizing these side effects. That means fewer emergency department visits and, hopefully, fewer admissions on the inpatient side of care.
AJMC®:Many institutions are using clinical pathways or clinical decision support tools to assist in driving patients and physician towards high-value treatments. When it comes to that shared decision-making process, is your institution using these tools, and if so, can you discuss the support structure in place for small cell lung cancer?
Haumschild: I'm thankful that our institution has embraced shared decision-making. As a matter of fact, it's actually a core value of our organization. I think it’s especially important in small cell lung cancer to make sure that everyone is using the most efficacious treatment. We want to drive the most appropriate utilization in the frontline setting, and one of the ways you do that is complemented with pathways—and pathways that are reinforced through order sets to provide a high standard of care across all our sites, whether you're a subspecialist or you're a community oncologist. The way to work together is to develop disease state working groups where you have shared decision-making between your community oncologist and your aerodigestive or lung subspecialist. That way you can have agreement on what's the best way to treat small cell lung cancer patients. We need to make sure that people are leveraging that triplet therapy with the PD-L1 inhibitor in that frontline treatment setting—and that they are knowing exactly how to pivot to second line to give their patients the best overall survival and progression-free survival. So, within these pathways, it can take away that variability, which allows us to build in some of that side effect management that we know is so important to reduce abandonment rates.
Ultimately, it allows us to continue to monitor our real-world evidence as more therapies come forward. We can include these data in pathways, and we can make updates those pathways as we get more institution-specific data to make sure that we're keeping in mind diverse populations. I think the last thing about pathways is that you can leverage real-world evidence to address health equity and reach underserved patients. You can make sure that you have pathways that fit not just the entire patient population but are considered [responsive] to the most underserved populations. So, that's what we do. It allows us to be effective, and it allows that patient to receive that same high level of care, whether they go to a subspecialist or community oncologist that's close to their home.
AJMC®: I'd like to dive a little bit deeper into the topic of shared decision-making. How are pharmacists and physicians and perhaps other practitioners at your institution collaborating and having the shared decision-making approach with patients? What is their role in driving high-quality outcomes in small cell lung cancer?
Haumschild: You've got to include multiple people of the care team, and I think that multidisciplinary approach allows patients to be most successful. How do we incorporate pharmacists? Well, pharmacists sit elbow to elbow with that physician provider as well as that advanced practitioner, as well as the clinic nurse—so they're seeing that patient in person. I think that's so valuable. But in addition, they’re also doing work on the back end, so they're developing order sets, they're developing monographs for these medications, and they're making sure that we're including the latest information, whether it be from [National Comprehensive Cancer Network] guidelines, from abstracts, or from research that we're doing internally here. With all that, you must build in not only great treatment pathways, but you must build in education for the patient. The reason I say that is if the patient expects one thing and you're not educating them on that subsequent therapy, ultimately, they could be confused. They may not feel good about dose reductions, and they may want to stop altogether.
So, our pharmacists actually sit in clinic. They work up patients next to their physicians and then they give recommendations on the treatments once those scans and a definitive diagnosis comes back from pathology. But in addition to that, we build out patient-specific education so the patient knows what their journey may be like. We educate them on why we're doing chemotherapy. Maybe we discuss why we're adding on a checkpoint inhibitor, and why immunotherapies are now providing additional benefit to the patient—and what side effects to anticipate. And we educate them on the supportive care medications we're providing them so that if there's any weight-limiting toxicities, they can report those to us. But they also have the medications on hand to take them to reduce any type of toxicity progression and ultimately, we talked on the importance about adherence. Stay adherent to your therapy but if you're having side effects when you do any type of dose reductions, let us know. That might be a normal part of your patient care journey. It doesn't mean that you're going to have less efficacious treatment. It just means you're going to be able to stay on treatment longer. And so, our pharmacists provide this education and lastly monitor these patients and do check-ins based on their different cycles to make sure that we're titrating their doses appropriately. And if there's any financial toxicity, we're engaging the right members of our patient assistance team to get them engaged and reporting that out through the electronic medical record and the provider.
AJMC®: Are there any other thoughts on the topic of small cell lung cancer that you’d like to share with your colleagues or our audience here at AJMC®?
Haumschild: Treatment of small cell lung cancer is changing, and we've got to make sure we’re on board and adopting those newer, innovative therapies earlier. But we also must recognize that with small cell lung cancer, not everyone's an expert. So, how do we leverage some of these pathways, or some of these order sets or standard approaches, into care so that we offer practitioners who see multiple solid tumor disease states the information they need to start patients on the right therapy early on? How do we incorporate education?
Patients are on the same page, and they have shared expectations around treatment. I think that's obviously extremely important. Again, how do we look forward to seeing the research breaking on some of these immunotherapies, so that we can leverage this information when these therapies are ready to be added to formulary? And then lastly, how do we leverage efficacy data from different cooperative group trials, such as atezolizumab and chemoradiation or durvalumab and some of these newer therapies, to provide better overall survival and reduce a lack of response in the second line or later?
And then lastly, I think we've got to be cost-conscious about these therapies. We've got to recognize that we can maybe take on some of these therapies on the front end. We worry about that patient’s out-of-pocket costs, but we might be able to decrease total cost of care if we get patients on the right therapy sooner. And then at the end of the day, we must recognize that there's high mortality for 5-year mortality, and 5-year survival rates are rather low right now, so we need to continue to enroll patients in clinical trials as appropriate to add to the body of data to provide more therapies for these patients.