Summary
First-line pembrolizumab plus etoposide significantly improved progression-free survival (PFS) and prolonged overall survival (OS) among patients with extensive-stage small cell lung cancer (ES-SCLC) when compared to placebo plus etoposide, according to data presented during an oral presentation at the ASCO 2020 Annual Meeting (Abstract 9001).
“SCLC is a very aggressive disease—one for which there have been few advances in the last 30 years,” noted study author Charles M. Rudin, MD, PhD, Chief of Thoracic Oncology Service and Co-Director of the Druckenmiller Center for Lung Cancer Research at Memorial Sloan Kettering Cancer Center.
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Original Article
Pembrolizumab Plus Chemo Improves Survival in Extensive-Stage Small-Cell Lung Cancer
Oncology Times
By Catlin Nalley
First-line pembrolizumab plus etoposide significantly improved progression-free survival (PFS) and prolonged overall survival (OS) among patients with extensive-stage small cell lung cancer (ES-SCLC) when compared to placebo plus etoposide, according to data presented during an oral presentation at the ASCO 2020 Annual Meeting (Abstract 9001).
“SCLC is a very aggressive disease—one for which there have been few advances in the last 30 years,” noted study author Charles M. Rudin, MD, PhD, Chief of Thoracic Oncology Service and Co-Director of the Druckenmiller Center for Lung Cancer Research at Memorial Sloan Kettering Cancer Center.
“It has been thought that immunotherapy may be a benefit to these patients,” he continued. “In particular, there's been data in recurrent disease demonstrating significant responses with pembrolizumab, some of which are durable, which led ultimately to its FDA approval for third-line or later use in metastatic SCLC.”
Study Details
KEYNOTE-604, a double-blind, phase III study, was designed to evaluate whether the addition of pembrolizumab to first-line chemotherapy in newly diagnosed ES-SCLC patients could improve outcomes.
The researchers randomized 453 patients with previously untreated ES-SCLC and no untreated CNS metastases 1:1 to pembrolizumab (200 mg Q3W) or saline placebo for up to 35 cycles plus 4 cycles of standard-dose etoposide. Primary endpoints included OS and PFS in the ITT population. Secondary objectives were overall response rate, duration of response, and safety.
With a median follow-up of 13.5 months, pembrolizumab plus etoposide significantly improved PFS in the ITT population (HR 0.75 [95% CI 0.61-0.91], P = 0.0023; median 4.5 vs. 4.3 months), according to Rudin.
At final analysis, the researchers reported that pembrolizumab plus etoposide prolonged OS, but the significance threshold was not met (HR 0.80 [95% CI 0.64-0.98], P = 0.0164; median 10.8 vs. 9.7 months).
“Progression-free survival was the clear, positive result,” noted Rudin. “We also saw an improvement in response rates, increasing from about 62 percent on the control arm to 70.6 percent on the pembrolizumab-containing arm.
“More importantly, we saw a subset of patients who really had durable responses on pembrolizumab,” he continued. “One of the take-home messages is that there is a group of patients who see a significant benefit from the addition of an immune checkpoint inhibitor. And so, one of the future challenges will be to really define biomarkers that might allow us to identify that sub-population that derives transformative benefit from these immunotherapy interventions.”
In terms of safety, Rudin noted that the treatment was well-tolerated. “The overall toxicities were similar on both arms,” he stated. “There were, as expected, immune-related adverse events associated with pembrolizumab, but those were actually quite similar to prior studies of single-agent pembrolizumab. Therefore, there are no new safety signal of concern.”
Ongoing Study
Findings from KEYNOTE-604, according to Rudin, adds to the growing literature regarding the benefit of immunotherapy.
“There have been two recently published studies—IMpower133 (atezolizumab) and CASPIAN (durvalumab)—looking at ways to augment chemotherapy for patients with newly diagnosed extensive-stage disease,” he said. “And, both of those studies demonstrated statistically significant survival advantage. The data from our trial further reinforces those data, showing the potential benefit of immune checkpoint inhibitor therapy in this context.”
When discussing what is next for the research, Rudin noted, “We were pleased to see an improvement in progression-free survival, although the extent of benefit is less than what we would hope.
“There's a subset of patients that derives long-term benefits from immunotherapy in SCLC, but there's a much larger set of patients who do not,” he concluded. “So, I think there's still a lot of work to do to try to understand how we can better activate the immune system for a larger proportion of these patients with this still pretty fatal disease.”
Catlin Nalley is a contributing writer.