Five-Year Survival Outcomes With Nivolumab Plus Ipilimumab Versus Chemotherapy as First-Line Treatment for Metastatic Non–Small-Cell Lung Cancer in CheckMate 227

Abstract

PURPOSE We present 5-year results from CheckMate 227 Part 1, in which nivolumab plus ipilimumab improved overall survival (OS) versus chemotherapy in patients with metastatic non-small cell lung cancer (mNSCLC), regardless of tumor programmed death ligand 1 (PD-L1) status. METHODS Adults with stage IV/recurrent NSCLC without EGFR mutations or ALK alterations and with tumor PD-L1 ≥1% or <1% (N=1739) were randomized. Patients with tumor PD-L1 ≥1% were randomized to first-line nivolumab plus ipilimumab, nivolumab alone, or chemotherapy. Patients with tumor PD-L1 <1% were randomized to nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy. Endpoints included exploratory 5-year results for efficacy, safety, and quality of life (QoL). RESULTS At 61.3 months’ minimum follow-up, 5-year OS rates were 24% versus 14% for nivolumab plus ipilimumab versus chemotherapy (PD-L1 ≥1%), and 19% versus 7% (PD-L1 <1%). Median duration of response was 24.5 versus 6.7 months (PD-L1 ≥1%) and 19.4 versus 4.8 months (PD-L1 <1%). Among patients surviving 5 years, 66% (PD-L1 ≥1%) and 64% (PD-L1 <1%) were off nivolumab plus ipilimumab without initiating subsequent systemic anticancer treatment by the 5-year time point. Survival benefit continued following nivolumab plus ipilimumab discontinuation due to treatment-related adverse events, with a 5-year OS rate of 39% (combined PD-L1 ≥1% and <1% populations). QoL in 5-year survivors treated with nivolumab plus ipilimumab was similar to the general US population through 5 years’ follow-up. No new safety signals were observed. CONCLUSION With all patients off immunotherapy treatment for ≥ 3 years, nivolumab plus ipilimumab increased 5-year survivorship versus chemotherapy, including long-term, durable clinical benefit regardless of tumor PD-L1 expression. These data support nivolumab plus ipilimumab as an effective first-line treatment for patients with mNSCLC.

Spatial multi-omics revealed the impact of tumor ecosystem heterogeneity on immunotherapy efficacy in patients with advanced non-small cell lung cancer treated with bispecific antibody

“…In addition, especially in the population with PD-L1<1%, the efficacy of NIVO+IPI combined regimen was superior to that of NIVO / IPI+chemotherapy in all aspects. 40 Therefore, these results also indicated that PD-L1 expression could not be a single indicator for predicting the efficacy of dual immunotherapy. For patients treated with bsAbs, it is more important to accurately identify biomarkers in the exclusion of ITH, rather than just using the traditional detection technique.…”

Radiomics and Delta-Radiomics Signatures to Predict Response and Survival in Patients with Non-Small-Cell Lung Cancer Treated with Immune Checkpoint Inhibitors

“…However, in the recently published Checkmate 227 update reporting the 5-year clinical outcomes of the trial, comparing first-line immunotherapy combination to chemotherapy in metastatic NSCLC, immunotherapy achieved substantial long-term clinical benefit regardless of PD-L1 expression. The 5-year OS rates in PD-L1 negative (<1%) patients were 19% (nivolumab plus ipilimumab) versus 7% (chemotherapy), which might lead to revisiting the actual clinical impact of this parameter [ 36 ]. Additionally, we have considered responders as any patient who had not progressed at 6 months, but we did not differentiate the different types of response in our models.…”

Clinical utility of inflammatory and nutritious index as therapeutic prediction of nivolumab plus ipilimumab in advanced NSCLC

“…Several recent clinical studies established the effectiveness of PD-1 blockade plus an anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibody as a rst-line treatment for advanced NSCLC [2][3][4] and malignant melanoma [5]. In particular, the combination of the nivolumab (Nivo) and the anti-CTLA4 antibody ipilimumab (Ipi) provided long-term survival (5-year survival rate: approximately 20%), even in NSCLC patients with PD-LI negativity [2]. However, the therapeutic biomarkers for anti-CTLA4 antibody e cacy remain unclear.…”