Background
5-yr outcomes of NADIM, a multicentre, single-arm phase II trial, N=46, of neoadjuvant chemoimmunotherapy in resectable stage IIIA NSCLC: neoadjuvant chemotherapy + nivolumab → surgery → 1 yr adjuvant nivolumab.
Interventions and follow up
Treatment: 3 cycles nivolumab 360 mg + paclitaxel 200 mg/m² / carboplatin AUC6 (neoadjuvant) → surgery → adjuvant nivolumab for 1 yr
Primary endpoint: 5-yr PFS and OS (descriptive)
mFollow up: 60 mo
Primary endpoint: 5-yr PFS and OS (descriptive)
mFollow up: 60 mo
Results
5-yr PFS (ITT): 65.0% (95% CI 49.4–76.9)
5-yr OS (ITT): 69.3% (95% CI 53.7–80.6)
5-yr PFS by pathology: ~92% with pCR vs ~60% without
5-yr OS by pathology: ~95.8% with pCR vs ~66% with residual tumor
Radiologic ORR (neoadjuvant): 76%
pCR rate: 34.8%
5-yr OS (ITT): 69.3% (95% CI 53.7–80.6)
5-yr PFS by pathology: ~92% with pCR vs ~60% without
5-yr OS by pathology: ~95.8% with pCR vs ~66% with residual tumor
Radiologic ORR (neoadjuvant): 76%
pCR rate: 34.8%
Adverse events
Overall: Grade ≥3 treatment-related AE 30% during neoadjuvant phase
Hematologic/metabolic: Increased lipase 7%, febrile neutropenia 7%
Adjuvant phase: Elevated serum amylase 8%, lipase 7%; no new safety signals on longer follow-up
Hematologic/metabolic: Increased lipase 7%, febrile neutropenia 7%
Adjuvant phase: Elevated serum amylase 8%, lipase 7%; no new safety signals on longer follow-up
Conclusions
Neoadjuvant chemotherapy plus nivolumab followed by adjuvant nivolumab produced durable 5-yr PFS (65%) and OS (69%) in resectable stage IIIA NSCLC. pCR was strongly associated with long-term survival, supporting pCR as a potential surrogate endpoint.
Key Limitations
Small single-arm phase II (N=46) without a comparator arm; stage IIIA only; descriptive survival endpoints; pCR-survival association exploratory.
Clinical Context
Provided early proof-of-concept for perioperative chemoimmunotherapy later confirmed in randomized phase III trials (CheckMate 816, KEYNOTE-671, AEGEAN); supports the perioperative chemo-IO approach now standard per ASCO/ESMO.