KEY TAKEAWAYS
- The phase 2 trial aimed to investigate the long-term clinical efficacy of neo ICB with nivo and nivo+ipi in NSCLC.
- The primary endpoints were to determine MPR, PCR, EFS, and OS.
- The Neo ICB with nivo or nivo+ipi shows promising long-term efficacy in resectable NSCLC; further research is needed.
Neoadjuvant (neo) and perioperative immune checkpoint blockade (ICB) have significantly transformed the management of resectable non-small cell lung cancer (NSCLC). These therapies have introduced new possibilities for improving patient outcomes.
Joshua Reuss and the team aimed to present the inaugural pooled analysis of 5-year clinical outcomes from 2 early-phase trials, NEOSTAR and CA209-259, investigating neo-ICB in NSCLC.
In NEOSTAR (NCT03158129), patients were randomly assigned (1:1) to receive IV nivolumab (nivo) 3mg/kg every 2 weeks (q2w) x 3 (doses) with or without IV ipilimumab (ipi) 1mg/kg on day 1 only. In comparison, CA209-159 (NCT02259621) involved patients in sequential arms with different combinations of nivo and ipi (nivo 3mg/kg q2w x 2, nivo 3 mg/kg q2w x 3 w/ I 1mg/kg on day 1 only, nivo 3mg/kg q2w x 3). Both trials included patients with stage I-IIIA NSCLC (AJCC 7th).
The team performed a meta-analysis of individual patient data to estimate the rates and hazard ratios (HR) for major pathologic response (MPR), pathologic complete response (PCR), event-free survival (EFS), overall survival (OS), and HR.
The results showed that 60 patients received nivo and 30 received nivo+ipi. The MPR rates were (28.1% (95% CI: 17.4, 42.1) and 33.3% (95% CI: 19.0, 51.7) for nivo+ipi. The PCR rates were (95% CI: 3.5, 18.5) and 26.7% (95% CI: 13.9, 45.0).
With a median follow-up of 68.4 months for nivo and 62.1 months for nivo+ipi, median EFS and OS were not reached. For the combined 90-patient cohort, MPR showed high 5-year EFS and OS rates of 74.0% (95% CI 52.9, 86.8) and 81.7% (95% CI: 61.4, 92.0), respectively. Patients with PCR had a 5-year EFS and OS of 77.5% (95% CI: 44.9, 92.2) and 85.5% (95% CI: 52.9, 96.2), respectively.
MPR showed a trend toward better EFS with nivo+ipi, and pre-treatment PD-L1 ≥1% was linked to significantly improved EFS with nivo. KRAS co-mutations with STK11, KEAP, and SMARCA4 were linked to worse EFS in nivo.
The study concluded that neo-ICB with nivo alone or combined with ipi shows promising long-term clinical efficacy in resectable NSCLC. Further biomarker-driven research is necessary to identify patient subgroups who would benefit from these therapies.
The trial was sponsored by M.D. Anderson Cancer Center.
Source: https://cslide.ctimeetingtech.com/esmo2024/attendee/confcal/show/session/117
Clinical Trial: https://clinicaltrials.gov/study/NCT03158129
Reuss J, Leung CH, Rosner S, et al. (2024). “Neoadjuvant nivolumab and nivolumab+ipilimumab in resectable non-small cell lung cancer: Combined analysis of 5-year outcomes from NEOSTAR and CA209-159,” Presented at ESMO 2024 (Abstract 1209MO).
