Interim findings from the NADIM ADJUVANT Phase III clinical trial conducted by the Spanish Lung Cancer Group (GECP) have unveiled promising evidence that adjuvant chemo-immunotherapy can significantly reduce the risk of disease recurrence in patients diagnosed with completely resected stage IB to IIIA non-small cell lung cancer (NSCLC). These results, which were presented at the prestigious International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer, mark a pivotal advancement in the postoperative management of early-stage NSCLC, a condition historically plagued by high relapse rates despite surgical intervention.
Surgical excision with curative intent (R0 resection) has long been considered the cornerstone of treatment in early-stage lung cancer, yet it fails to fully eliminate the threat of disease progression. NSCLC, representing the majority of lung cancer cases, retains a formidable risk of recurrence, which continues to drive significant cancer-related mortality worldwide. This clinical challenge underscores the urgent need for innovative adjuvant strategies designed to eradicate residual microscopic disease and enhance long-term survival outcomes.
The NADIM ADJUVANT trial stands out as the first randomized Phase III study to rigorously evaluate the addition of nivolumab, a PD-1 immune checkpoint inhibitor, to standard platinum-doublet chemotherapy in the adjuvant setting. Building upon encouraging perioperative data from the precursor NADIM and NADIM II trials, this study explores whether continued immunotherapeutic pressure following definitive surgery and chemotherapy can sustain antitumor immune responses and prevent recurrence.
Between January 2021 and December 2022, a total of 206 patients across 30 Spanish hospitals were enrolled and randomized in a 1:1 ratio. Participants in the control arm received adjuvant chemotherapy consisting of carboplatin dosed at an area under the curve (AUC) of 5 combined with paclitaxel at 200 mg/m² administered on a tri-weekly schedule for four cycles, followed by observation only. The experimental group received identical chemotherapy followed by concomitant administration of nivolumab at 360 mg every three weeks during four chemotherapy cycles, and subsequent maintenance nivolumab at 480 mg every four weeks for six additional cycles.
The primary endpoint of this pivotal trial was disease-free survival (DFS), a critical measure reflecting the length of time patients remain free from detectable tumor recurrence following treatment. Secondary endpoints included overall survival (OS) and comprehensive safety assessments to monitor treatment-related toxicities. Additionally, the study incorporated cutting-edge monitoring of minimal residual disease (MRD) via circulating tumor DNA (ctDNA) analysis, employing the Guardant Reveal platform to sensitively detect subclinical tumor burden after surgery.
Mariano Provencio, MD, PhD, the study’s lead investigator from Hospital Universitario Puerta de Hierro Majadahonda, revealed that after a median follow-up of 34 months, median DFS had not yet been reached in either treatment arm, indicating durable responses. Notably, the first quartile of DFS was significantly prolonged in the experimental arm at 30.98 months compared with 17.01 months in the control group. The three-year relapse incidence further underscored the benefit, with only 26.7% of patients in the nivolumab plus chemotherapy arm experiencing recurrence versus 40.1% in patients receiving chemotherapy alone.
A vital component of the study was the exploration of MRD as a prognostic biomarker. Postoperative detection of MRD was strongly associated with inferior DFS outcomes in the experimental cohort, with a hazard ratio of 5.7 and a statistically significant p-value of 0.045. These results affirm the critical role of sensitive ctDNA-based MRD assessment in stratifying patients’ risk profiles and tailoring postoperative therapeutic approaches more precisely.
While augmenting adjuvant chemotherapy with nivolumab demonstrated clear efficacy, safety profiles remained an essential consideration. Grade 3 or higher treatment-related adverse events occurred in 26.2% of patients receiving the combined regimen, compared to 14.5% in the control arm during the adjuvant phase. This indicates that while immune-related toxicities are more common with the addition of nivolumab, they remain manageable and within acceptable limits given the potential clinical benefit.
Dr. Provencio emphasized, “The interim findings from the NADIM ADJUVANT trial offer compelling evidence that incorporating nivolumab into adjuvant chemotherapy regimens can substantially reduce recurrence risk in patients with completely resected stage IB to IIIA NSCLC. These data not only build upon prior perioperative trials but also pave a path forward for integrating immunotherapy into the standard adjuvant treatment paradigm.” He further highlighted the necessity of continued follow-up to robustly define the long-term survival impact and confirm durable remission benefits.
These results resonate deeply within the lung cancer research community, as they provide concrete evidence from a randomized Phase III trial endorsing adjuvant immunotherapy’s role beyond advanced and unresectable disease stages. The implications extend to refining clinical guidelines, optimizing patient selection, and advancing personalized medicine by incorporating MRD and other biomarkers into postoperative care.
The trial’s success also reaffirms the potential of immune checkpoint blockade to engage and sustain antitumor immunity in micrometastatic disease settings where traditional treatments fall short. This aligns with the broader paradigm shift towards leveraging the host’s immune system to achieve durable tumor control and potentially cure in earlier disease stages.
In addition to its clinical impact, the NADIM ADJUVANT study exemplifies collaborative research excellence, uniting a broad network of Spanish hospitals and specialists who collectively endeavored to address a critical unmet need. Their shared commitment culminates in data that will influence global clinical practice and inspire further research to build upon these foundational findings.
As the oncology community awaits final primary endpoint results and longer-term overall survival data, the NADIM ADJUVANT findings signal a watershed moment in the adjuvant management of NSCLC. They herald a future where integrated multimodal treatment strategies incorporating surgery, chemotherapy, immunotherapy, and biomarker-driven monitoring become the standard for improving patient prognosis.
The International Association for the Study of Lung Cancer (IASLC) continues to foster pivotal dialogues and disseminate groundbreaking discoveries such as these during its annual World Conference on Lung Cancer (WCLC). This gathering remains the premier global forum for accelerating advancements in understanding and treating lung and thoracic malignancies through multidisciplinary collaboration.
In summary, the NADIM ADJUVANT Phase III trial advances the field of thoracic oncology by demonstrating that the addition of nivolumab to adjuvant chemotherapy significantly improves disease-free survival outcomes while maintaining an acceptable safety profile in completely resected stage IB–IIIA NSCLC. The integration of MRD testing further enhances the precision of postoperative management. These results promise to transform clinical practice and improve survival for thousands of patients worldwide confronting early-stage lung cancer.
Subject of Research: Adjuvant chemo-immunotherapy in completely resected stage IB–IIIA non-small cell lung cancer (NSCLC)
Article Title: Interim Results from the NADIM ADJUVANT Phase III Trial Indicate Significant Benefit of Nivolumab Addition to Chemotherapy in Reducing Recurrence of Early-Stage NSCLC
News Publication Date: September 8, 2025
Web References:
https://www.iaslc.org/
Keywords: Lung cancer, Non-small cell lung cancer (NSCLC), Adjuvant therapy, Chemo-immunotherapy, Nivolumab, Disease-free survival, Minimal residual disease, ctDNA, Phase III clinical trial, NADIM ADJUVANT, Immunotherapy, Oncology
