Keytruda Shows Promise in Advanced Small Cell Lung Cancer

Previously treated patients with advanced small cell lung cancer (SCLC) benefitted from immunotherapy, according to recent study findings presented at the 2019 American Association for Cancer Research Annual Meeting.

Researchers found that patients who had at least two lines of prior therapy responded well and experienced manageable side effects when treated with Keytruda (pembrolizumab), an immune checkpoint inhibitor given intravenously. Keytruda binds to PD-1, a type of protein, blocking it, which helps the immune system kill cancer cells. The immunotherapy agent has shown success and received approval from the Food and Drug Administration (FDA) for other cancer types, such as melanoma and advanced non-small cell lung cancer.

“Up to 70% of patients with SCLC have advanced disease at diagnosis,” Hyun Cheol Chung, M.D., Ph.D., professor at Yonsei Cancer Center, Yonsei University College of Medicine in Seoul, Republic of Korea, said in a press release. “Current treatment guidelines specify a variety of first- and second-line treatment options. However, for patients who require third-line therapy, there are no specific recommendations and prognosis is very poor.”

In the study, the researchers used data from two clinical trials — KEYNOTE-028 and KEYNOTE-158 — that examined the use of Keytruda in patients with SCLC. KEYNOTE-028 included patients with PD-L1—positive tumors only and KEYNOTE-158 included anyone with PD-L1 expression.

From the two trials, 83 patients were eligible for analysis. Most patients were men, median age was 62 and 64% received two prior lines of therapy.

Based on the pooled analysis, 19.3% of patients had a partial (14 patients) or complete (two patients) responses to Keytruda. And nine of the 16 patients had responses that lasted at least 18 months. At 24 months, the median progression-free survival, or time from treatments to disease worsening or progression, was 13%. Overall survival was 21%.

“There are some patients with small cell lung cancer who get a very nice response to this therapy. It’s not uniform. But when it happens, it appears to be durable and very valuable,” study author Janice M. Mehnert, M.D., director of the Phase I/Investigational Therapeutics Program at Rutgers Cancer Institute of New Jersey, said in an interview with CURE®.

Grade 3 and 5 side effects were seen in the patient population (10 and 3 patients, respectively). Grade 5 side effects included pneumonia, insufficient blood flow to the gastrointestinal tract and brain disease, damage or malfunction. Immune-related side effects or infusion reaction were experienced by 21% of patients. Five patients discontinued treatment because of side effects. “It’s like you’re aggravating your immune system to wake it up and fight your cancer, but sometimes you aggravate it so much you wind up getting a side effect that’s a result of your immune system being turned on,” Mehnert said. “Across the board, we know that these side effects happen and most of the time they’re manageable.”

Based on these data, the FDA granted a priority review to the new supplemental Biologics License Application for Keytruda, which could lead to a faster approval of the drug for patients with advanced SCLC.

Last month, the FDA approved the first immunotherapy for initial treatment of patients with extensive-stage SCLC: Tecentriq (atezolizumab) in combination with chemotherapy showed an overall survival of 12.3 months compared with 10.3 months in patients who received chemotherapy alone.

“We know that (immunotherapy) is active. But we have to learn how to optimize it,” said Mehnert. “We still have clinical trials that we need to conduct. And from there the holy grail is biomarkers. How do you figure out when the patient is in front of you in the office that this is going to work and spare them chemotherapy? How do we know when we need to give one drug versus two drugs?”