ASCO 2025 Update on CheckMate 816: Stephen Liu, MD, Shares Insights

Stephen Liu, MD, Director of Thoracic Oncology at Georgetown University, joined Lung Cancers Today to discuss the CheckMate 816 data presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.

Patrick M. Forde, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, presented the late-breaking abstract during an oral abstract session at the 2025 ASCO Annual Meeting.

The CheckMate 816 study evaluated neoadjuvant nivolumab plus chemotherapy versus chemotherapy alone, followed by surgery, in patients with stage IB-IIIA resectable NSCLC, Eastern Cooperative Oncology Group performance status of less than or equal to 1, and no known EGFR or ALK alterations. The study is now the “only neoadjuvant-only immunotherapy phase 3 trial to demonstrate a statistically and clinically significant” 5-year overall survival (OS) benefit for a resectable solid tumor, according to Dr. Forde’s presentation.

Dr. Liu said that this is a “very important update” to CheckMate 816, as it is the first time that an OS benefit has been shown with this approach.

“While we know that the neoadjuvant component alone improved pathologic complete response, improved event-free survival, we did need to see an improvement in overall survival to know that this was a viable strategy and that some patients could be spared that adjuvant component,” Dr. Liu said. “And here at this meeting, we did see an improvement in overall survival.”

With a median follow-up of 68 months, the neoadjuvant nivolumab plus chemotherapy regimen demonstrated a statistically significant OS benefit compared with chemotherapy alone (median [95% CI], not reached [NR] versus 73.7 months [47.3–NR]; HR [95% CI], 0.72 [0.523–0.998]; P = 0.0479).

The 5-year OS rate was 65% in those receiving the combination regimen, compared with 55% in those receiving chemotherapy alone. The OS “favored” the combination regimen in the subgroups of patients that were defined by tumor PD-L1 expression, baseline disease stage, and histology, according to Dr. Forde’s presentation.

Dr. Liu explained that this OS data cements that this regimen is a “viable option, with only three doses of neoadjuvant nivolumab improving outcomes.” However, questions remain in terms of patient selection for the regimen and where this neoadjuvant strategy should be used instead of a perioperative regimen.

“That still remains to be determined, and there are likely some patients who do benefit from that adjuvant component and some that may not need further therapy, sparing them cost and potential toxicity,” Dr. Liu said.

There may be some hints in the subset data from the trial, Dr. Liu said, noting that the benefit was “clearly greater” in patients who had tumors with PD[L]-1 expression. In addition, those who achieved pCR showed a better survival than those who did not, with a five-year survival rate of 95% in those who achieved a pCR with nivolumab plus chemotherapy, compared to 56% in those who did not achieve a pCR.

“Are patients who don’t achieve pathologic CR the ones that will benefit from the adjuvant component? This study is not designed to ask that,” Dr. Liu said. “However, we have other trials ongoing that really will give us that answer.”

Circulating tumor DNA (ctDNA) also seemed to be relevant in this context, he explained.

“Those that cleared ctDNA had better survival at five years, whether receiving chemotherapy or nivolumab plus chemotherapy,” Dr. Liu said. “Those that did not clear ctDNA did have worse outcomes. Could this be potentially a factor to help stratify patients?”

With further work to be done in stratifying patients and determining which patients may be best suited for the regimen, Dr. Liu said there’s also another key question on the horizon.

“Now the question is, can we further improve outcomes with the adjuvant component? We need a little bit more data and a study designed to answer that specific question,” he concluded