Evolving Role of PD-L1 and Neoadjuvant Immunotherapy in Resectable NSCLC

In this episode, Evolving Role of PD-L1 and Neoadjuvant Immunotherapy in Resectable NSCLC, the lung cancer experts explore the following questions:

How does PD-L1 status impact your management decisions for patients with resectable NSCLC?

Let’s start with the CheckMate-816 trial, which examined nivolumab plus chemotherapy vs chemotherapy alone as neoadjuvant treatment for patients with resectable NSCLC. What was the trial design and the key efficacy and safety data seen in this trial?

The panelist examined how PD-L1 status plays a supportive but not exclusive role in guiding perioperative management for resectable NSCLC, helping to estimate the likelihood of benefit from immunotherapy while not serving as an absolute requirement for treatment selection. Higher PD-L1 expression is associated with greater pathologic response rates to neoadjuvant chemoimmunotherapy, but meaningful benefit has been observed across PD-L1 subgroups, so most eligible patients are considered for immunotherapy-based approaches regardless of expression level. PD-L1 may also inform discussions about the magnitude of expected benefit and help prioritize perioperative immunotherapy in borderline surgical candidates or those with higher-risk pathologic features. In clinical practice, PD-L1 is interpreted alongside stage, resectability, comorbidities, and molecular testing results, particularly to avoid immunotherapy in patients with targetable driver mutations who may derive greater benefit from targeted strategies.

The phase 3 CheckMate 816 trial randomized patients with resectable stage IB–IIIA NSCLC to three cycles of platinum-doublet chemotherapy with or without nivolumab prior to surgery. The addition of nivolumab significantly improved pathologic complete response rates and event-free survival compared with chemotherapy alone, without compromising surgical feasibility or increasing perioperative complications. Major pathologic response rates were also substantially higher with the combination, and the benefit was observed regardless of PD-L1 expression, though numerically greater in PD-L1–positive tumors. Rates of grade 3–4 treatment-related adverse events were similar between arms, and there were no unexpected immune-related toxicities that delayed surgery. These results established neoadjuvant nivolumab plus chemotherapy as a standard-of-care option for appropriate patients with resectable NSCLC.

Throughout the conversation, the experts provide a comprehensive reflection on the field and the factors that may shape how clinicians approach care moving forward.

The next episode in this series, Perioperative Immunotherapy Advances: Insights from CheckMate-77T and KEYNOTE-671, features the panelists advancing their conversation on key clinical trials in NSCLC.