Dr Tom Stinchcombe Highlights Challenges in Treating SCLC

The lack of biomarkers remains a challenge in small cell lung cancer, but studies are trying to divide patients into subsets to identify those that would benefit most from treatments, explained Tom Stinchcombe, MD, medical oncologist, Duke Cancer Institute.

In an interview with The American Journal of Managed Care® (AJMC®), he discussed the use of real-world evidence, future research priorities, and more.

In the first part of his interview, Stinchcombe had covered second-line treatment options, their side effects, efficacy, and costs.

AJMC: How can health care providers ensure that patients with metastatic small cell lung cancer receive appropriate and timely access to novel therapies?

Stinchcombe: I think this is an important question across all lung cancer. Some of the things that we can do is make sure that the patients are diligently staged and have the appropriate pathological diagnosis up front. With small cell lung cancer, many times the patients are symptomatic and it's an aggressive disease. Our window of opportunity to enroll a patient on trials may be shorter than it is with other diseases. So, we need to have trials readily available, and our trials have to reflect the nature of the disease in terms of the eligibility criteria and making them as convenient as possible for patients to enroll.

AJMC: How can the use of real-world evidence improve the understanding of the treatment landscape for metastatic small cell lung cancer?

Stinchcombe: Most of us recognized our trials are the idealized circumstances in terms of patient selection and the management, but many of our patients would not meet the eligibility criteria for a trial. We're faced with a situation where the patient is present and the data is absent. I think real-world data provides us another venue to collect data on how well these drugs are tolerated, the approximate efficacy in terms of real-world progression-free survival, and treatment duration. So, the efficacy metrics change, but I think they do give us an impression of a broader patient population—maybe more patients with a borderline performance status or slight organ dysfunction.

AJMC: How can biomarkers be used to guide treatment decisions for metastatic small cell lung cancer?

Stinchcombe: This has been one of the biggest disappointments within small cell lung cancer that we haven't really been able to develop a biomarker. Patients with non–small cell lung cancer have benefited tremendously from biomarker-driven care. Even within immunotherapy, the predictive value of PD-L1 status in small cell lung cancer is not validated. That's one of the challenges that we have.

I think there are some interesting studies trying to break these into different subsets of small cell lung cancer. I think there's about 4 different subsets. As an academic community, we've done the retrospective studies, but we have to prospectively collect this data and perform the subtype analysis and really demonstrate that it improves patient outcome either as prognostic information or in predictive value towards immunotherapy, and to determine if there's a subset that benefits more from immunotherapy.

AJMC: What are the priorities for future research and development in the treatment of metastatic small cell lung cancer?

Stinchcombe: The molecular subtypes and defining these into subgroups of small cell lung cancer that may be more susceptible to different immunotherapies or develop other therapies. That's one of the priorities. I think most of us see the checkpoint inhibitors as adding value to chemotherapy, but we would really like to try and see if we can have an additional immunotherapy. I'm speaking specifically about the trials of CTLA-4 and TIGIT agents. The 4-drug combinations didn't really pan out and that's a disappointment.

The other thing that we're going to work on is the bispecific antibodies. There are a number of them in development right now and these have new mechanisms of action and may have a really durable benefit for patients. I think that's our current focus in the second line.

AJMC: What are you working on in small cell lung cancer that you're excited to share?

Stinchcombe: My colleague at Duke, Neal Ready, MD, PhD, heads our small cell lung cancer subgroup of things, and he's looked at a number of antibody-drug conjugates looking at specific markers. SEZ 6 antibody-drug conjugate was one of the trials that we recently had a trial, and there other agents in this class. My hope is that these may improve the therapeutic efficacy to adverse event ratio among small cell lung cancer, and maybe replace standard chemotherapy in the second-line setting. This is a complex task when consider biomarker development and making sure that you have the correct dose. But I think that that's a promising venue. We've seen progress in non–small cell lung cancer with HER2 mutations with antibody drug conjugates. Hopefully, they'll bring another therapeutic option to our small cell lung cancer patients.