Lung Cancer

Recent Progress in Small-Cell Lung Cancer Therapy

November 2022 – Lung Cancer
Dana Taylor

Lung cancer is divided into 2 main categories. According to the American Cancer Society, the majority, about 85%, of lung cancers are non–small-cell lung cancer (NSCLC), and only about 15% of cases are small-cell lung cancer (SCLC). Each type of lung cancer is further divided into subtypes.

It is important to know the main type of lung cancer, because the treatment for patients with SCLC is very different from the treatment for patients with NSCLC.

Most of the recent progress made in new therapies, including immunotherapies and targeted therapies, has been for patients with NSCLC, but encouraging progress has been finally made in the past 2 years in the diagnosis and treatment of patients with SCLC.

Immunotherapy for Small-Cell Lung Cancer

Charles M. Rudin, MD, PhD

At the 2022 World Conference on Lung Cancer, Charles M. Rudin, MD, PhD, Chief of the Thoracic Oncology Service at Memorial Sloan Kettering Cancer Center in New York City, presented new results from a phase 3 clinical trial called KEYNOTE-604 using the immunotherapy Keytruda (pembrolizumab), a PD-1 inhibitor, in patients with SCLC.

This ongoing study is investigating the benefit of immunotherapy with Keytruda plus chemotherapy compared with chemotherapy plus placebo for the first-line treatment of patients with extensive-stage SCLC.

“The 3-year overall survival rate was more than 2.5 times higher among patients who received pembrolizumab [Keytruda] and [chemotherapy]. Patients who completed 35 cycles of pembrolizumab had durable responses,” Dr. Rudin said.

In this study, patients with untreated extensive-stage SCLC received either Keytruda or placebo for up to 3.5 years (35 cycles), plus 4 cycles of chemotherapy.

The overall survival and the time without disease progression were better with Keytruda plus chemotherapy compared with placebo plus chemotherapy.

About 2 years after completing therapy with Keytruda, the average survival was not reached, meaning that patients were still responding to immunotherapy, and the 2-year survival rate after completing 35 cycles of immunotherapy (a total of 5.5 years) with Keytruda was 72.2%.

These results are encouraging and support the ongoing investigation of using immunotherapy-­based combinations for patients with SCLC, Dr. Rudin noted.

First Immunotherapy for Extensive-Stage Small-Cell Lung Cancer

In March 2020, Imfinzi (durvalumab), a PD-L1 inhibitor became the first immunotherapy, in combination with chemotherapy, to be approved by the FDA for first-line treatment of patients with extensive-stage SCLC.

“Patients with extensive-stage small-cell lung cancer continue to face a poor prognosis, and finding new medicines to improve outcomes in this setting has been a formidable challenge…making this an important new first-line treatment option for patients,” said Jonathan Goldman, MD, Associate Professor of Hematology and Oncology, UCLA Medical Center, Santa Monica, California.

Personalized Medicine in Small-Cell Lung Cancer

Unlike NSCLC, in which many genetic and genomic biomarkers have been discovered and are now being treated with a large number of targeted therapies designed to attack those biomarkers, to date, SCLC has only been associated with a few genomic biomarkers, such as the TP53 gene. But so far, no therapies have been approved for this biomarker for patients with SCLC.

Therefore, no targeted therapies are currently available for patients with this type of lung cancer, but researchers have recently found certain genetic subtypes that may provide a new direction for the treatment of some patients with SCLC.

At the 2022 European Society for Medical Oncology conference and the 2022 World Conference on Lung Cancer, researchers discussed new developments in the diagnosis of SCLC, highlighting new information that may provide new treatment directions in the future. This is a promising step for patients with SCLC.

In recent studies, several genetic, or transcriptional, subtypes of SCLC have been identified, which may lead to personalized therapy, specifically with immunotherapy, for patients with one of those subtypes.

The 4 major transcriptional subtypes identified, based on gene activation in SCLC, are currently labeled SCLC-A, SCLC-N, SCLC-P, and SCLC-I. These 4 subtypes represent a game-changing approach that may help to develop a personalized treatment of patients with SCLC.

Researchers are trying to determine if different subtypes of SCLC react differently to treatment. To date, there have been promising results suggesting that SCLC-I subtypes may have better responses to immunotherapy options, whereas subtypes SCLC-N and SCLC-P may be better treated with targeted therapies. More research is needed before these subtypes in SCLC can be translated into clinical practice for patients, but this is a promising step toward incorporating a personalized approach to the treatment of patients with SCLC.

Metastatic Small-Cell Lung Cancer

William Jeffery Petty, MD

In June 2020, the FDA approved a new treatment called Zepzelca (lurbinectedin), an intravenous alkylating drug, for the treatment of adults with metastatic SCLC that had progressed during or after chemotherapy.

“Seeing first-hand the aggressive nature of small-cell lung cancer, and knowing that the large majority of those diagnosed will experience relapse, I am excited to see an effective new treatment demonstrating durable responses,” said William Jeffery Petty, MD, Professor, Hematology and Oncology, Wake Forest School of Medicine.

“For doctors, patients and their families, Zepzelca is an important and much-needed addition to the treatment landscape for relapsing small-cell lung cancer,” Dr. Petty said.

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Last modified: November 16, 2022

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