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First-line Nivolumab Plus Chemotherapy Did Not Meet the Primary Endpoint of Overall Survival in Non-Squamous NSCLC

Results of the CheckMate 227 - part 2 final analysis
12 Dec 2019
Anticancer agents & Biologic therapy;  Cancer Immunology and Immunotherapy;  Lung and other thoracic tumours

Although overall survival (OS) in patients with non-squamous non-small cell lung cancer (NSCLC) with first-line nivolumab plus chemotherapy versus chemotherapy did not reach statistical significance and the primary endpoint was not met, groups of patients with squamous NSCLC and all randomised patients did show improved OS with the combination treatment. Additionally, all groups of patients treated with nivolumab/chemotherapy showed prolonged progression-free survival (PFS) and improved objective response rates (ORR) over chemotherapy alone. These findings from the phase III CheckMate 227 trial were presented at the ESMO Immuno-Oncology Congress 2019 in Geneva, Switzerland (11-14 December).

Prof. Luiz Paz-Ares of the Medical Oncology Department, University Hospital 12 de Octubre and Universidad Complutense and CiberOnc in Madrid, Spain presented findings from part 2 of the final analysis of data from the multi-part, randomised, open-label, phase III CheckMate 227 (NCT02477826) study of first-line nivolumab plus chemotherapy versus chemotherapy alone.

CheckMate 227enrolled 755 patients with chemotherapy-naive, ECOG performance status 0–1, stage IV or recurrent NSCLC. The patients were required to have no sensitising EGFR/ALK alterations.

Following 1:1 randomisation, 377 patients received nivolumab at 360 mg for up to 2 years plus histology-based chemotherapy for up to 4 cycles, progression, or unacceptable toxicity, and 378 patients received the same chemotherapy regimen. Baseline characteristics between treatment arms were generally balanced. The patients were stratified by histology (squamous versus non-squamous sex, and PD-L1 expression status (<1% versus ≥1%). Pemetrexed maintenance was available to patients with non-squamous NSCLC. The primary endpoint was OS with nivolumab plus chemotherapy as compared with chemotherapy in patients with non-squamous NSCLC and a secondary hierarchical endpoint was OS in all randomised patients.

With minimum follow-up of 19.5 months in the groups of 270 and 273 patients with non-squamous NSCLC who were treated with the nivolumab combination and chemotherapy, respectively, no statistically significant improvement in OS was seen with nivolumab plus chemotherapy over chemotherapy alone; median OS was 18.8 versus 15.6 months with the respective treatments (hazard ratio [HR] 0.86; 95,62% confidence interval [CI], 0.69–1.08; p = 0.1859). A total of 156 (57.8%) and 164 (60.1%) OS events had occurred with nivolumab/chemotherapy versus chemotherapy and the one-year OS rates were 67.3% versus 59.2%, respectively.

The impact in OS was more evident in patients with squamous histology and in the overall population. In the 107 patients with squamous NSCLC receiving nivolumab plus chemotherapy and 105 on chemotherapy, median OS was 18.3 versus 12.0 months (HR 0.69; 95% CI, 0.50-0.97) and 12-month OS rates were 66.1% versus 48.5%, respectively.

In the overall study population, 377 patients on nivolumab/chemotherapy had median OS of 18.3 months compared to 14.7 months in those treated with chemotherapy (HR, 0.81; 95% CI, 0.67–0.97), and the 12-month OS was 66.9% versus 56.2%, respectively.

PFS and ORR favoured nivolumab plus chemotherapy across all three groups

Median PFS in patients with non-squamous NSCLC was 8.7 versus 5.8 months (HR 0.67; 95% CI, 0.55–0.82), and the 12-month PFS rates was 39.5% versus 25.7% with nivolumab/chemotherapy versus chemotherapy, respectively. The ORRs were 48.1% versus 29.3% with the respective treatments.

Regarding patients with squamous histology, median PFS was 7.1 with nivolumab plus chemotherapy versus 4.4 months with chemotherapy (HR 0.51; 95% CI, 0.37–0.70), and the 12-month PFS rates were 31.7% versus 9.3%. The ORRs with the respective treatments were 59.8% versus 32.4%.

In the patients overall, median PFS was 8.4 months with nivolumab plus chemotherapy versus 5.5 months with chemotherapy (HR 0.62; 95% CI, 0.52–0.73), and the 12-month PFS rates were 37.3% versus 21.3%. The ORRs with the respective treatments were 51.5% versus 30.2%.

Treatment-related Grade 3/4 adverse events occurred in 45% and 35% of all nivolumab/chemotherapy- and chemotherapy-treated patients, respectively. No new safety signals were appreciated in the nivolumab plus chemotherapy treatment group.


Although CheckMate 227 - part 2 did not meet the primary endpoint of OS with nivolumab plus chemotherapy compared with chemotherapy in the group of patients with non-squamous NSCLC, OS was prolonged with nivolumab plus chemotherapy in patients with squamous NSCLC and in all randomised patients in the descriptive analysis. Both PFS and the ORR favoured nivolumab plus chemotherapy over chemotherapy across all three groups, including patients with non-squamous NSCLC.


This trial was funded by Bristol-Myers Squibb. 


LBA3 - Paz-Ares L, Ciuleanu TE, Yu X, et al. Nivolumab (NIVO) + platinum-doublet chemotherapy (chemo) vs chemo as first-line (1L) treatment (tx) for advanced non-small cell lung cancer (aNSCLC): CheckMate 227 - part 2 final analysis.

Last update: 12 Dec 2019

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