Navigating Complexities and Options in the SCLC Treatment Landscape

Federico Albrecht, MD

The current standard of care treatment for patients with small cell lung cancer (SCLC) is chemotherapy in combination with immunotherapy, according to Federico Albrecht, MD. Recent advances in the space are supported by findings from the IMpower133 (NCT02763579) and CASPIAN (NCT03043872) studies.^1,2

In the first study, IMpower133, the PD-L1 inhibitor atezolizumab (Tecentriq) was compared with standard chemotherapy among patients with newly diagnosed extensive stage-SCLC (ES-SCLC). The combination led to improved rates of survival in this patient population.

With the combination of atezolizumab, carboplatin, and etoposide, patients had a median overall survival (OS) of 12.3 months vs 10.3 months with chemotherapy alone. For progression-free survival, rates were 5.2 months with atezolizumab and chemotherapy vs 4.3 months with chemotherapy alone.

Then, in CASPIAN, durvalumab (Imfinzi) added to platinum-etoposide and tremelimumab (Imjudo) given in addition to platinum-etoposide improved OS rates among treatment-naive patients with ES-SCLC, showing a median OS of 13.0 months with the addition of durvalumab compared with 10.3 months with platinum-etoposide alone.

In an interview with Targeted Oncology^TM, Albrecht, oncologist/hematologist at Miami Cancer Institute of Baptist Health South Florida, further discussed advances to treatments for patients with SCLC and considerations when treating difficult cases.

lung with cancer cells: © catalin - stock.adobe.com

Targeted Oncology: What is standard practice on testing for a patient with small cell lung cancer? Who is being cared for at Miami Cancer Institute?

Albrecht: Small cell lung cancer is a highly aggressive neuroendocrine carcinoma, accounting for more or less 15% of all lung cancers that we see at the Miami Cancer Institute. Almost all patients with this type of cancer have a history of smoking, either as current smokers or former smokers. Clinical characteristics of small cell lung cancer that distinguish [it] from non–small cell lung cancers are rapid tumor growth and early metastasis formation, so it has a worse prognosis. Small cell lung cancer is categorized in 2 stages: limited stage and extensive stage. The limited stage is defined when the radiation oncologist could encompass all the disease sites on 1 treatment field.

At the Miami Cancer Institute, our approach after histologic confirmation of small cell lung cancer is to complete the staging process. This includes obtaining a CT scan of the chest, abdomen, and pelvis with IV contrast, or better, a PET scan. We also prioritize the brain MRI to detect early asymptomatic brain metastases or a CT scan if brain MRI is not done, but finding what's going on in the brain is very important. In patients that present with pleural effusion, a limited stage-small cell lung cancer, we always conduct a thoracentesis to ensure accurate determination of the disease extension. To enable rapid initiation to systemic therapy, we ask our skilled thoracic surgeons to promptly place a protocol.

Given that the small cell carcinoma is a systemic disease, early initiation of systemic therapy holds an immense importance. We strongly emphasize the need to avoid any delays in systemic therapy. For example, to accommodate the start of radiation therapy, we ideally start the first cycle of chemotherapy as soon as possible. However, we have to realize that we cannot delay radiation therapy too much. Multiple studies have shown that early concurrent chemoradiation therapy offers significant survival benefits compared with delaying the status of traditional surgery. In small cell lung cancer, there are 2 crucial factors that significantly impact the treatment outcomes. One is the timely initiation of systemic chemotherapy and the second is the prompt completion of radiation therapy. These 2 factors act as risk modifiers, emphasizing the importance in achieving a favorable result. At Miami Cancer Institute, we have a protocol that prioritizes the initiation of treatment for hospitalized patients. Under this protocol, the patients that are hospitalized will start cycle number 1 as soon as the diagnosis is made in the hospital, even before the discharge. Prior, they get a radiation oncology appointment or a radiation oncology consultation.

Can you share a story of a difficult case of small cell lung cancer that you've had?

I encountered a case involving a 67-year-old, heavy smoker, who was still actively smoking at the time of diagnosis. The patient presented with a rapidly progressing small cell lung cancer exceeding extensive mediastinal involvement, liver metastasis, and pulmonary metastasis as confirmed by the staging PET scan. A brain MRI did not reveal any metastasis. Apart from hypercholesterolemia and hypertension, the patient had no significant other comorbidities. Clinically, the patient experienced significant cough, chest pains, and more. Her performance status was assessed as 2 and, in our minds, that is essential to differentiate whether the patients' compromised performance status is attributed to the disease itself or to the cause of the comorbidities. To expedite the initiation of systemic therapy, a thoracic surgeon promptly inserted a protocol.

I made a decision to start this patient rapidly on carboplatin and etoposide in combination with immunotherapyin this case, atezolizumab. Thankfully, the patient responded remarkably well and experienced a rapid alleviation of cough and shortness of breath, with a complete resolution of chest pains just after the first and the second cycles. After cycle number 1, pure oxygen saturation levels improved, shortness of breath improved, and the cough completely resolved. [The patient] was able to completely be cured through 4 cycles of chemotherapy without problems. That is a case where a patient presents with a lot of disease and there is a cure. Daily activities are being affected, but not because the patient has comorbidities. It is because of cancer. Therefore this is a type of patient that you can treat aggressively. With the addition of immunotherapy, that made a huge difference. The patient is doing well and has improved completely to a performance status of 0.

Can you talk about the clinical trial research that supports atezolizumab-containing regimens?

This development, which is the addition of immunotherapy to primary chemotherapy, represents the first major advancement in the management of this disease in the last 30 years. This is important. As you know, small cell lung cancer is an aggressive and rapidly progressing malignancy. While typically responding to initial chemotherapy, it often recurs in a matter of months, resulting in a poor prognosis. Two, crucial phase 3 trials have been conducted in recent years. The first is called IMpower133, which was initially published in the New England Journal of Medicine in 2018, and subsequently updated and published in the Journal of Clinical Oncology. This study demonstrated that adding a PD-L1 monoclonal antibody to the standard treatment of carboplatin and etoposide improved survival. Furthermore, patients were able to continue receiving immunotherapy as maintenance treatment until this progression.

The second study, known as the CASPIAN trial, investigated the use of durvalumab and another PD-L1 monoclonal antibody in combination with carboplatin or cisplatin and etoposide. It was first published in The Lancet and it also received recent updates. Again, both trials showed an improvement in survival rates for the first time in more than 20 years. Both of these agents have now been approved by the FDA and have become the standard of care for patients with extensive-stage small cell lung cancer. Currently, research is underway to determine whether similar benefits can be achieved in patients with limited stage-small cell lung cancers.

Are there any other treatment options that you consider for this patient?

Chemotherapy with immunotherapy is the cornerstone in treatment for small cell lung cancer. The standard of care involves a combination of cisplatin or carboplatin with etoposide and the addition of immunotherapy if the patient has small cell lung cancer, extensive disease. It is important to understand and know the [adverse] effects of these therapies that we can discuss.

Can you share a story of a patient who experienced an adverse event from small cell lung cancer treatment? How did you work with other doctors from multiple disciplines to mitigate this toxicity?

In a 65-year-old patient who was diagnosed with extensive-disease small cell lung cancer, after completing 4 cycles of carboplatin, etoposide, and atezolizumab this month, the patient transitioned to maintenance atezolizumab. During the maintenance phase, she developed an immune-related dermatitis, primarily affecting her hands and palms. The patient suffered from significant pain. Additionally, she experienced worsening shortness of breath and cough. A CT scan of the chest revealed evidence of pneumonitis. I collaborated closely with our dermatology oncology service that we have at Miami Cancer Institute to promptly see and address the patient's condition. The dermatology team initiated topical steroids and antibiotics while our group of experienced pulmonologists evaluated her for immune related pneumonitis.

With the addition of oral steroids, her condition improved rapidly. She became asymptomatic, and her rash and her dermatitis also improved. Once both [adverse] effects or immune-related [adverse] effects were resolved, the patient was able to resume therapy with continued tolerance. It is important to note that patients who develop an immune-related [adverse] effect often experienced a robust immune response against the cancer cells and tended to fare better in the long run. Therefore, we consider these [adverse] effects to be acceptable in the context of achieving an effective immune activation against cancer cells.

What other advice do you have for your peers about treating a patient with small cell lung cancer today?

The most crucial advice I have for my colleagues treating patients with small cell lung cancer is to recognize that small cell lung cancer is a systemic disease, even in cases of limited stage disease. Therefore, it is imperative to initiate systemic therapy promptly, as soon as possible, without any delays. Avoid postponing chemotherapy, systemic chemotherapy to accommodate radiation therapy schedule. Instead, begin chemotherapy and then eventually, that gives time for the radiation oncologist to start readily for cycle number 2.

The other important advice is to not delay the start of radiation therapy either, because both treatments in limited disease-small cell lung cancer are important and, as I say, are important risk modifiers. The sooner you do that, the better the patient's outcome. The other recommendation is to maintain open and fluid communication with the radiation oncologist because radiation therapy plays a vital role in the treatment of lung cancer. Rigorous implementation of the radiation therapy can significantly impact the outcomes of this disease.

Remember that the approach for patients with limited disease-small cell lung cancer has a curative intent. That means we're trying to cure these patients. In the case of extensive stage-small cell lung cancer, we are incorporating immunotherapy. It is crucial to use immunotherapy in every single patient with extensive disease unless there is a contraindication. It is essential to be vigilant of any immune-related [adverse] effects because early intervention can prevent severe complications. Additionally, I would like to remind my colleagues to stay informed about ongoing trials in this field because numerous advancements are being made, and I am confident that we will continue to see improvement in outcomes in this tough disease.

REFERENCES:

1. Horn L, Mansfield A, Szczęsna A, et al. First-Line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018; 379(23):2220-2229. doi: 10.1056/NEJMoa1809064

2. Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus platinum–etoposide versus platinum–etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019;394(10212):1929-1939. doi: 10.1016/S0140-6736(19)32222-6