Long-term benefits of combined immunotherapy over chemotherapy in non-small cell lung cancer

In the 5-year landmark analysis of the phase 3 CheckMate 227 trial, the first-line immunotherapy combination nivolumab plus ipilimumab demonstrated long-term clinical benefits over chemotherapy in patients with metastatic non-small cell lung cancer (NSCLC), regardless of PD-L1 expression level. A substantial proportion of responders remained treatment-free for ≥3 years after treatment discontinuation, with a high quality-of-life.

Part 1 of the CheckMate 227 trial (NCT02477826) randomised 1,189 patients with metastatic NSCLC and PD-L1 expression levels ≥1% 1:1:1 to nivolumab plus ipilimumab, nivolumab alone, or platinum-doublet chemotherapy. Part 2 randomised 550 patients with this condition but with PD-L1 expression levels <1% to nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy alone. Previous analyses of this trial showed that patients on nivolumab plus ipilimumab had higher overall survival (OS) and progression-free survival (PFS) rates than patients on chemotherapy [1]. Prof. Julie Brahmer (Sidney Kimmel Comprehensive Cancer Center, Australia) presented the 5-year update of CheckMate 227 [2].

In the subgroup of patients with PD-L1 expression levels ≥1%, 24% of the patients on the immunotherapy combination were alive compared with 14% in the chemotherapy arm (median OS 17.1 vs 14.9 months; HR 0.77). After 5 years, 12% of the patients in the immunotherapy combination arm were still progression-free, but only 2% in the chemotherapy arm. Moreover, 28% of the patients in the nivolumab plus ipilimumab arm had an ongoing response, even though the study drug had been discontinued for ≥3 years, and this was only 3% in the chemotherapy arm.

In the stratum of patients that had PD-L1 expression levels <1%, the OS rates after 5 years were 19% and 7%, favouring the combination therapy arm over the chemotherapy arm (HR 0.65). The PFS rates (12% vs 2%) and duration of response rates (21% vs not applicable) after 5 years demonstrated a similar benefit in the combination arm as was seen in the PD-L1 ≥1% subgroup of patients. Interestingly, in 5-year survivors treated with nivolumab plus ipilimumab, the quality-of-life scores were at or above the US norms for up to 4.5 years, irrespective of PD-L1 expression level.

1. Hellman MD, et al. N Engl J Med. 2019;381(21):2020–2031.
2. Brahmer JR, et al. Five-year survival outcomes with nivolumab (NIVO) plus ipilimumab (IPI) versus chemotherapy (chemo) as first-line (1L) treatment for metastatic non–small cell lung cancer (NSCLC): Results from CheckMate 227. LBA9025, ASCO Annual Meeting, 3–7 June, Chicago, IL, USA.

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Posted on 5 August 202215 February 2024