Dr Konstantinos Leventakos Highlights the Challenge of Treating Metastatic SCLC

Immunotherapy has been game changing for treatment small cell lung cancer (SCLC), but the US health care system needs to be better organized in order to speed referrals of patients to centers with the capability to improve outcomes, said Konstantinos Leventakos, MD, PhD, assistant professor of oncology and medicine, Mayo Clinic, Rochester, Minnesota.

In an interview with The American Journal of Managed Care^® (AJMC^®), Leventakos discussed standard treatment options for SCLC, treatment selection for patients, and the role of immunotherapy.

In the first part of the interview, Leventakos discussed diagnosis of SCLC and the need for biomarkers that predict treatment response.

AJMC: What are some of the standard treatment options for small cell lung cancer, and how do they vary depending on the stage and severity of the disease?

Leventakos: Clinically, small cell lung cancer can be limited stage where chemotherapy and radiation are the mainstay or it can be extensive stage where chemotherapy and immunotherapy includes the addition of durvalumab or atezolizumab on top of platinum with etoposide. Symptomatic brain metastasis in the setting of the extensive stage may need radiation as needed. Prophylactic cranial radiation has been evaluated mainly in the limited stage and these patients are suggested to meet with radiation oncology specialists to discuss the options and have close monitoring with MRIs. Regarding immunotherapy in the limited stage, we're still waiting for the results of randomized clinical trials.

AJMC: Can you expand on the limitations of these standard treatment options such as quick relapses and poor long-term outcomes?

Leventakos: In the limited stage, the use of chemotherapy and radiation can cure a minority of patients. In the extensive stage, initially, the majority of patients have a good response to chemotherapy and immunotherapy and, actually, these patients feel better and live longer. With the use of the immunotherapy, we have been able to increase overall survival by about 3 months. It is more interesting that we have increased number of patients that are alive years after the diagnosis. Unfortunately, the majority of patients will relapse.

AJMC: What are some of the challenges associated with treating metastatic small cell lung cancer?

Leventakos: The treatment of metastatic small cell lung cancer is many times challenging, because many patients are symptomatic or have hematologic and biochemical abnormalities due to their disease. Many patients have comorbidities commonly associated with previous or current history of smoking. Small cell lung cancer treatment needs to be done urgently, and delays during the diagnosis can negatively impact the outcome of the treatments. Once small cell lung cancer recurs, second-line treatment is indicated but still more research is needed to optimize these treatments.

AJMC: How do you approach selecting the most appropriate treatment option for individuals with metastatic small cell lung cancer and what factors do you consider when making these decisions?

Leventakos: The treatment of newly diagnosed small cell lung cancer is chemotherapy with immunotherapy for the majority of the patients. There are only minor differences between the 2 FDA-approved agents. Thus, the decision between durvalumab and atezolizumab is made on a case-by-case basis. When it comes to second-line treatment, the options depend on the time between progression and the last dose of chemotherapy of the first-line therapy. In this case, options include repeating the initial chemotherapy, lurbinectedin, topotecan, or other agents.

In our institution, our first step is to evaluate the patient for clinical trials since we all understand the need for more clinical trial data for this disease. All of our patients are evaluated for clinical trials in the newly diagnosed or recurrent stage. If they are not candidates for clinical trials, then we'll proceed with standard treatment as I already described.

AJMC: What role does immunotherapy play in the treatment of metastatic small cell lung cancer and what are the challenges in its development?

Leventakos: Definitely immunotherapy has been game changing in small cell lung cancer. The addition of atezolizumab or durvalumab has improved outcomes. More immunotherapy agents are currently undergoing clinical trials. One recent trial, including tiragolumab presented at ASCO 2022, did not provide additional benefit but more clinical trials are ongoing. For the development not only of immunotherapy but targeted therapies, as well, we need more results.

Given how fast this disease progresses, how urgently patients need treatments, many times we do not perform biopsies in the recurrent stage for clinical reasons. That limits the availability of tissue for better immunologic and genetic characterization of the disease, especially in the recurrent stage where the disease is more aggressive. I strongly believe that better organization of the health care system for early referral of patients to centers with capability of translational and clinical research will improve the outcomes of this disease.