Immune-checkpoint inhibitors targeting the PD-1–PD-L1 axis have improved the outcomes of patients with advanced-stage non-small-cell lung cancer (NSCLC), including after definitive chemoradiotherapy for unresectable stage III disease. However, whether these agents are effective in patients with resectable stage I–IIIA NSCLC — for whom therapeutic advances have been limited — remains unknown. Now, data from a pilot neoadjuvant study provide new insights.

In this study, 22 patients were allocated to receive 2 doses of the anti-PD-1 antibody nivolumab (3 mg/kg every 2 weeks) starting ~4 weeks before resection of stage I (19%), stage II (48%), or stage IIIA (33%) NSCLC. After receiving one dose, one patient was deemed ineligible and another had grade 3 pneumonia and proceeded to surgery without receiving a second dose. Four other patients had grade 1–2 adverse events. Importantly, treatment did not delay surgery for any patient and of the 21 primary tumours removed, 20 were completely resected.

Of the patients with complete resection, nine (45%) had a major pathological response ( ≤10% viable residual tumour cells), including three complete responses (15%), and eight (40%) had disease downstaging. At a median of 1 year after surgery, recurrence-free survival was 80%: three patients had lymph-node or metastatic recurrence (one died and two had responses to salvage therapies lasting >1 year); one patient without recurrence had died of an unrelated injury.

Major and complete pathological responses occurred irrespective of tumour PD-L1 status before treatment. By contrast, the percentage of viable residual tumour was inversely correlated with pretreatment tumour mutation burden (rs −0.75, P = 0.008) and predicted neoantigen load (rs −0.78, P = 0.005). Moreover, expansion of peripheral blood and intratumoural T cells, including some neoantigen-specific clones that were undetectable before treatment, was detected after PD-1 blockade.

These results demonstrate the feasibility and promising activity of neoadjuvant PD-1 blockade in patients with early stage NSCLC; further testing of this approach is warranted.