Changes to the SCLC Treatment Landscape Stirs Up Hope for Oncologists

Sagun Shrestha, MD

After several decades of limited options, patients with small cell lung cancer (SCLC) now have multiple treatment options, including the immune checkpoint inhibitors (ICIs) atezolizumab (Tecentriq), and durvalumab (Imfinzi).

Prior to the FDA approvals of atezolizumab and durvalumab, chemotherapy made up the standard of care for patients with SCLC. The backbone of treatment for these patients was platinum-etoposide chemotherapy.

However, the FDA approved these 2 ICIs in 2019 and 2020, respectively, in combination for patients with extensive-stage SCLC based on findings from the IMpower133 trial (NCT02763579) and CASPIAN study (NCT03043872).

Now, these options have filled this patient population with hope after years of limited options.

“All the drugs equally have a competitive response rate, especially in terms of using them as a maintenance drug. I think that changes how we are or how we have been treating extensive-stage small cell lung cancer,” Sagun Shrestha, MD, told Targeted Oncology^TM, in an interview.

In the interview, Shrestha, medical director of medical oncology at City of Hope Phoenix, evaluated new developments and clinical trials for patients with extensive-stage SCLC.

Targeted Oncology: Can you discuss some of the recent advances in the small cell lung cancer space?

Shrestha: In small cell lung cancer over the last several decades, the treatment of choice has been the same with the platinum-etoposide backbone. Over the last few years, the main change we have had, and the exciting thing is about adding immune checkpoint inhibitors. One of the main drugs we use is atezolizumab [Tecentriq] or durvalumab [Imfinzi], and that has really given more of an improvement in overall survival and decreased the chance of recurrence over time. That has changed the landscape of how we treat extensive-stage small cell lung cancer.

Can you discuss some of the newer studies that are being explored on anti PD-1 therapy in the first-line setting?

There have been several studies going on, but none of them have been FDA-approved yet for early-stage small cell lung cancer. There is the CASPIAN trial with immunotherapy, and the addition of pembrolizumab [Keytruda]. Even now, we can add pembrolizumab as 1 of the other immune checkpoint inhibitors, but we still prefer the atezolizumab and durvalumab at the present time. All of them are showing improvements in overall survival, and a decrease in disease-free progression has been improved by adding immunotherapy.

What are some recent trials that you can highlight in this space?

The CASPIAN trial is 1 which is promising, but all the drugs equally have a competitive response rate, especially in terms of using them as a maintenance drug. I think that changes how we are or how we have been treating extensive-stage small cell lung cancer.

What are some challenges that community oncologists are facing in the space?

Just because of how small cell lung cancer is, they have a very rapid doubling time with a high growth fraction, how most of them present at a late stage, [and] the development of early metastasis, the main thing we face that by the time we see patients is that the majority of are in the late stage of disease. When we are faced with a late-stage disease, even for limited-stage, the median survival is around 15 to 30 months, and the 5-year survival is around 10% to 13%. For extensive-stage, this goes down to a median survival of around 8 to 13 months, and the 5-year survival is just 1% to 2%. Overall, the prognosis is so poor.

At the same time, the small cell lung cancers are very sensitive to chemotherapy and sensitive to radiation. The initial responses we get quickly, a couple even in the first 2 rounds of chemotherapy, and they get a great response. But the problem here is being able to hold the disease-free progression for a longer period. That period is very short. Now, by adding the checkpoint inhibitors, we have been able to improve not just the overall survival, but the disease-free progression.

How do you envision the treatment landscape evolving over the next 5 to 10 years?

We are doing a lot of screening for smokers. For people who are chronic smokers, we are doing the low-dose CAT scans. [This is] like for breast cancer where we do mammograms, that's the standard of care. Now, we are promoting more and saying we need to do low-dose CT scans for patients who are chronic smokers. We can catch them at an earlier stage. That makes a whole lot of difference. In the next 5 to 10 years, we should be able to diagnose small cell lung cancer earlier in these patients, because it is a disease for smokers. If we can have all these patients who are smokers able to do the CAT scan and get them diagnosed early, I think the overall prognosis is going to change. I'm hoping that in the next couple of years we can add the checkpoint inhibitors earlier for the earliest stage, even for stage II. I think that that will change our perspective of how we treat small cells, how their prognosis will be, and how their prognosis will improve.

What advice do you have for community oncologists when treating patients with small cell lung cancer?

Having a team approach is very important. Sometimes we think that for small cell, there is no role for the surgeon or the radiation. That's not the case. I feel that the team approach, having all patients being seen by a medical oncologist, a thoracic surgeon, and a radiation oncologist, makes a whole lot of difference. For instance, most of the time for small cell, we say that surgery is not an option. But if it is stage I or small nodule, still having the surgeon involved and having it removed, I think, gives a better prognosis. Then, the role of radiation. Most of the time, the treatment of choice, especially for extensive-stage disease, is chemotherapy with immunotherapy. For instance, if there is disease which is improved after chemotherapy, adding radiation because they are radiosensitive is an important part. The other is for the earliest stage. If the disease is improved and there is no disease, that response is great. Then adding prophylactic cranial radiation or radiation to the brain to prevent recurrence in the brain is important. The team approach, as we have in like a cancer hospital setting, should be the case in any community practice too.

Apart from that, the support system, like counseling for smoking, is important. I think for every patient who is still a smoker, helping them with smoking cessation is an important part of it. For all our patients who are smokers, we let them have smoke counseling, have the pulmonary rehab, the pulmonologist involved, and have the team approach. I didn't mention the pulmonologist, but they're a big part of it in our hospital. Every patient that comes sees the pulmonologist and the whole team. Seeing the pulmonologist, seeing the rehab, smoking cessation counseling, and the psychological aspect of it, we have a psychologist who sees the patient so that emotional support is there, is another important part of it for when patients are going through it. Whenever [a patient] gets a diagnosis of small cell lung cancer, most of them talk about saying that dense kind of thing, but when they get the support system from everyone, it's not just a medical oncologist treating the patient, but a whole team of people.