The advent of neoadjuvant and perioperative immune checkpoint blockade (ICB) has significantly transformed the management of resectable non-small cell lung cancer (NSCLC). The inaugural pooled analysis of 5-year clinical outcomes derived from 2 early-phase trials of neoadjuvant ICB in NSCLC, namely NEOSTAR and CA209-159, was presented at ESMO 2024.
In the NEOSTAR trial (NCT03158129), patients were randomized 1:1 to receive intravenous nivolumab (Nivo) at a dosage of 3 mg/kg every 2 weeks for 3 doses, either in combination with intravenous ipilimumab (Ipi) at 1 mg/kg administered on the first day or as a monotherapy. The CA209-159 trial (NCT02259621) involved patients being allocated to sequential treatment arms: Nivo at 3 mg/kg every 2 weeks for 2 doses, followed by Nivo at 3 mg/kg every 2 weeks for 3 doses with Ipi at 1 mg/kg on day 1 only, and finally Nivo at 3 mg/kg every 2 weeks for 3 doses. Both studies included patients with stage I-IIIA NSCLC as classified by the American Joint Committee on Cancer staging manual, 7th edition. A meta-analysis of individual patient data was conducted to adjust for cohort effects, aiming to estimate the weighted rates of major pathologic response (MPR), pathologic complete response (PCR), event-free survival (EFS), overall survival (OS), and the corresponding hazard ratios (HRs).
A total of 60 patients received treatment with Nivo, while 30 patients were treated with NivoIpi. The median age of both cohorts was 66 years, and most patients in each cohort were former or current smokers (Nivo: 85.0%; NivoIpi: 90.0%). The MPR rates were recorded at 28.1% for the Nivo cohort and 33.3% for the NivoIpi cohort. PCR rates were 8.3% for Nivo and 26.7% for NivoIpi. With a median follow-up duration of 68.4 months for Nivo and 62.1 months for NivoIpi, the median EFS and median OS were not achieved in either treatment group. In the combined cohort of 90 patients, those with MPR exhibited a 5-year EFS of 74.0% and a 5-year OS of 81.7%. Patients with PCR demonstrated a 5-year EFS of 77.5% and a 5-year OS of 85.5%. MPR demonstrated a correlation with a trend of enhanced EFS in the NivoIpi group, but not in the Nivo group. In the Nivo group, a pretreatment PD-L1 expression of ≥1% was linked to a notable improvement in EFS. Furthermore, in the Nivo group, the presence of a known KRAS co-mutation alongside STK11, KEAP, and/or SMARCA4 was associated with a significantly poorer EFS, a trend not observed in the NivoIpi group.
Neoadjuvant ICB with Nivo and NivoIpi shows promising long-term clinical effectiveness in patients with resectable NSCLC. It is essential to conduct biomarker-driven studies to determine which patient subgroups would derive benefit from either neoadjuvant single or combined ICB therapies.
Source: Reuss J, Leung CH, Rosner S, et al. Neoadjuvant nivolumab and nivolumab+ipilimumab in resectable non-small cell lung cancer: combined analysis of 5-year outcomes from NEOSTAR and CA209-159. Barcelona, Spain, & online: presented at ESMO Congress 2024; abstract 1209MO.