Despite New Agents in SCLC, Prolonged Survival Remains an Unmet Need

In a Pharmacy Times® interview, Megan May, PharmD, BCOP, FHOPA, FAPO, clinical oncology pharmacy specialist with Baptist Health Lexington, discussed the evolving treatment landscape for patients with small cell lung cancer (SCLC), including those with extensive stage (ES-SCLC) and limited-stage (LS-SCLC) disease. She notes optimism with new treatments in the space, lurbinectedin (Zepzelca; Jazz Pharmaceuticals) tarlatamab (Imdelltra; Amgen), after not seeing any changes in decades. Despite these innovations, there is still an ongoing need to improve the survival rates of patients because of the disease’s aggressiveness. May urges health care professionals to stay up to date on ongoing developments as these agents are studied further.

Pharmacy Times: Can you introduce yourself?

Megan May, PharmD, BCOP, FHOPA, FAPO: My name is Megan May, I'm a clinical oncology pharmacy specialist at Baptist Health Lexington in Lexington, Kentucky. We are a large community hospital, and I am primarily in an outpatient cancer center.

Pharmacy Times: How has the treatment landscape for SCLC evolved in recent years?

May: So, compared to non-small cell lung cancer (NSCLC), SCLC has not had as many breakthroughs in therapeutics, but the first-line treatment using a platinum [and] etoposide combination has remained mostly unchanged for the last 30 years until recently. Fortunately, now we have the addition of immunotherapy to chemotherapy that's improved outcomes in treatment-naive [patients with] extensive stage SCLC (ES-SCLC). So, there's 2 main stages for SCLC, we have limited-stage SCLC (LS-SCLC) and ES-SCLC.

To start with LS-SCLC, like I said, there haven't been major advances in LS-SCLC for decades, until recently. The current standard of care is concurrent chemotherapy and radiotherapy, but most patients will relapse within 2 years of treatment, and the median overall survival (OS) is about 25 to 30 months. Consolidation therapy with a PD-1 immune checkpoint inhibitor durvalumab (Imfinzi; AstraZeneca) for up to 24 months is set to become the new standard of care for these patients with LS-SCLC. These findings were presented at [American Society of Clinical Oncology] (ASCO) Congress 2024, and it showed that the phase 3 ADRIATIC trial (NCT03703297) represented the first major practice change in the treatment of LS-SCLC in nearly 40 years.

Historically, the treatment of first-line ES-SCLC was platinum-based chemotherapy in combination with etoposide; second-line treatment was topotecan (Hycamtin; GSK). The development of immune checkpoint inhibitors in this setting has finally changed this treatment algorithm. Now in the frontline setting, we have carboplatin or cisplatin with etoposide plus either atezolizumab (Tecentriq; Genentech) or durvalumab for 4 to 6 cycles, followed by atezolizumab or durvalumab as a maintenance therapy until disease progression.

For years, the only things we had in the second-line setting [were] topotecan or irinotecan (Camptosar; Pfizer), but as of [June] 2020, we now have the [accelerated] approval of lurbinectedin (Zepzelca; Jazz Pharmaceuticals), and then more recently, in 2024, we have the approval of tarlatamab (Imdelltra; Amgen), both in the second-line setting. So now, we have 4 agents we can choose between. The use of these agents has been shifting to the newer agents with lurbinectedin and tarlatamab, because they do have a better toxicity profile, and so, it's really exciting to have more agents in this space now.

Pharmacy Times: In what ways have immune checkpoint inhibitors changed first-line treatment for SCLC, and what factors determine if patients are a good candidate?

May: The durable benefit observed with the addition of either a PD-1 or PD-L1 inhibitor to platinum and etoposide has really modified the therapeutic strategies that we recommend in patients with the LS-SCLC or ES-SCLC after several decades. This is particularly remarkable in such an aggressive disease, where historically, it had been challenging to overcome the long-term survival benefit obtained with a platinum/etoposide combination. Up to 6 weeks from completing radiotherapy until the start of immune checkpoint inhibitor consolidation is what is recommended. There's some data that even says the sooner the better, and you can start immunotherapy within 2 weeks of post-radiation therapy. This is particularly good for patients that have a good performance status, if they have residual thoracic disease, and they have low-bulk extra thoracic metastatic disease.

Pharmacy Times: What are the most critical gaps that still need to be addressed in SCLC research?

May: The entire space of small cell lung cancer is still a high unmet need, because, though we do have these newer agents that are in our treatment algorithm, there's still a high unmet need to prolong survival in these patients due to the aggressiveness of this disease. Some other things that I think are gaps that are going to hopefully be coming to light [are] what is the appropriate sequence of these new agents. Specifically, like we talked about with tarlatamab and lurbinectedin, how do you make that decision between which one is best for your patients, and we really need to be personalizing treatment for our patients with SCLC.

Another important gap that I think we're quickly filling is setting up these cancer clinics in order to be able to administer the bispecific antibodies like tarlatamab. We really need to make sure these clinics have the infrastructure so they're able to best care for the patients and be able to administer these more novel agents for patients that have SCLC, so they're getting the best treatment.

Pharmacy Times: Any final or closing thoughts?

May: I think SCLC is a really exciting topic right now, you know, we did not have many advances for decades, and now we've had several in just the last few years. So, it really is a hopeful treatment that we're seeing that can hopefully help these patients that, in the past, really did not have a positive outcome to be looking for. And so, I just encourage everyone to continue to research these medications, and then for clinical practitioners, making sure we stay most up to date on the treatment algorithm, since it is now continuously updating in the patients with both LS-SCLC and ES-SCLC.