Upfront Immunotherapy Options in Patients with Advanced Small Cell Lung Cancer

Small cell lung cancer (SCLC) remains challenging to treat because of its aggressive nature, and for decades there have been limited therapy advancements. However, in recent years, immunotherapy has transformed the way certain patients can be treated upfront.

Clinical trials combining immunotherapies, or drugs that boost a person’s immune system to help fight the cancer, with chemotherapy have shown positive results for patients with extensive-stage disease. This means that their cancer has spread throughout the lung, to the other lung, to lymph nodes or other parts of the body, such as the brain.

“Essentially, these (combinations) are game-changers that have transformed how we treat patients with extensive-stage SCLC. We have a new standard of care,” Dr. Jason Niu, a thoracic oncologist and director of the Lung Cancer Program at the Banner MD Anderson Cancer Center, said in an interview with OncLive®, a sister publication of CURE®.

Specifically, Niu referred to two clinicals trials, IMpower133 and CASPIAN, which both showed survival benefits for patients.

Findings from the Impower133 trial led to the Food and Drug Administration’s (FDA) approval of Tecentriq (atezolizumab) in combination with chemotherapy in March 2019. Patients saw a 30% reduction in the risk of death. “(Prior to the IMpower133 trial), the median overall survival for patients with extensive-stage SCLC was historically about 10 months,” Niu said. “IMpower133 was the first time, in the past four decades, where there was an increase in overall survival for these patients. Now, most thoracic oncologists have been using atezolizumab (and chemotherapy) for about a year.”

However, he explained that follow-up from this trial has been short so it’s important to follow these patients longer to see the long-term survival benefits.

In the phase 3 CASPIAN trial, the combination of Imfinzi (durvalumab) and chemotherapy lowered the risk of death by 27%, which led to the FDA granting a priority review designation in December 2019. Although not yet approved, the National Comprehensive Cancer Network has recommended its use in the front-line setting, according to Niu.

For patients whose disease progresses following initial treatment, Niu explained that other immunotherapy agents, such as Keytruda (pembrolizumab), Opdivo (nivolumab) and Yervoy (ipilimumab) can be used.

In addition, lurbinectedin, a new chemotherapy compound, has shown encouraging overall survival results. A clinical trial that included 105 patients with platinum-sensitive and platinum-resistant SCLC showed up to a 45% response rate and an 11-month median overall survival.

Patients also seemed to tolerate the drug well. “We mainly see hematologic toxicities, which are manageable from a medical oncology standpoint,” Niu said. “As such, I fully expect this agent to be approved soon.”

Yet the challenge that remains in the front-line setting is identifying potentially targetable biomarkers, Niu explained. “Biomarkers are needed to better inform which patients are most likely to respond to immunotherapy,” he said.