Disclosure: Mark G. Kris, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AstraZeneca; Roche/Genentech; Ariad Pharmaceuticals

Received a research grant from: Pfizer Inc; PUMA; Roche/Genentech

This is Mark Kris, going over developments in small cell lung cancer in 2024 that have advanced therapy in the field. I think the most dramatic one is the long overdue emergence of checkpoint inhibitors.

With durvalumab following concurrent chemotherapy and radiation for limited-stage small cell lung cancer showing clear benefits in extensive stage disease, it seems to me we're going to see the same benefits with limited stage disease. In the clinical trial reported this year, there was a near doubling of overall survival, from 33 to 66 months, by the addition of durvalumab after concurrent chemotherapy and radiation in limited-stage small cell lung cancer. I think that is now our new standard of care.

Complicating things, though, are the data. Looking at atezolizumab in limited-stage patients, the benefit was not as clear. This raises the question of: Which drug do you use? You have every reason to think that atezolizumab would be as effective as durvalumab.

Clearly, both drugs have been shown to be effective in extensive-stage patients and are standards of care. However, we have conflicting data. I think we know what to do with our patients in this situation, but we don't quite know how to process the data from atezolizumab. It's been presented, but more data are going to come out to help us understand that.

Another and more difficult decision for us is the appearance of tarlatamab. This is our first bispecific T-cell engager for the treatment of lung cancers. I think people have seen clear benefit from this agent. There is a 40% major response rate. Those responses are generally meaningful for the patients. They're durable -- more than half of the responses last 6 months, about a quarter last more than 9 months, and they're clearly important.

However, there are other drugs available in this area. Many chemotherapy drugs have activity, and depending on how long after the initial benefit the recurrence occurs, our go-to is to repeat the standard drugs we started at, either cisplatin or carboplatin and etoposide. The benefits there are usually very evident, and the greater the time from the conclusion of initial therapy to the recurrence, the more likely it is to help.

Balancing against the clear benefit of tarlatamab in 40% of patients and the long responses is the disease-free survival, which is less than 5 months. Balancing against the 40% response rate is the 50% incidence of cytokine release syndrome.

Again, many patients with recurrent, small cell lung cancer are not well. I think, particularly in those patients who have had the standard etoposide and platinum agents, this can be a tough decision on the appropriateness of those therapies [since] most institutions require hospitalization and [there is] also the adverse effects of therapy as well.

Particularly in light of the other therapies available, repeating the initial therapy and other agents, when you look at the phase 2 activity of drugs second line for small cell [lung cancer], many drugs have activity in the 20%-40% range. Exactly how much additional benefit comes from a drug like tarlatamab is something that we're going to have to figure out as time goes on. There are no randomized data at this point.

This is another tough decision for doctors. For patients, this is another therapy that can be helpful, but which patients are the right ones? Should tarlatamab be the second treatment or maybe the third? That's a tough decision and it's one we're going to have to make.

In 2024 for small cell [lung cancer], there's a clear benefit of durvalumab in limited-stage disease. Tarlatamab is another drug that can provide benefit to our patients, but how to choose patients, particularly for the tarlatamab, is another tough decision point for us. Again, you have to enlist the patient as to what their expectations are and what degree of adverse effects they would be willing to face to achieve that benefit, which frankly, doesn't affect the majority of patients.

That's a tough decision, and one that we're going to have to make. We're going to have to explain and work through our discussions with patients in order to decide if it represents the best therapy.