OA03.05 Analysis of Early Survival in Patients with Advanced Non-Squamous NSCLC Treated with Nivolumab vs Docetaxel in CheckMate 057

Abstract

Background: Nivolumab significantly improved OS versus docetaxel in patients with previously treated advanced non-squamous NSCLC (CheckMate 057; NCT01673867). KaplanÀMeier OS curves for nivolumab and docetaxel crossed at w7 months, suggesting nonproportional hazards between arms.

Patient Selection for Anti-PD-1/PD-L1 Therapy in Advanced Non-Small-Cell Lung Cancer: Implications for Clinical Practice

“…Whether this is due to the chemotherapy responder population being enriched with patients with immunologically 'hot' tumors is unknown. A post hoc multivariate analysis of CheckMate 057 demonstrated that patients with poor prognostic factors, including progressive disease as the best response to prior treatment and a shorter time since the last treatment, and/or more aggressive disease together with low or no PD-L1 expression, had a higher risk of death on nivolumab in the first 3 months of treatment versus docetaxel [71]. It will be important to evaluate whether the length of disease-free survival after previous treatment is a reflection of pre-existing immune responses as has been reported in cervical cancer [72].…”

Immunotherapy in Non-Small-Cell Lung Cancer: A Bridge Between Research and Clinical Practice

“…Despite the significant survival benefit of ICIs for a large proportion of patients with advanced NSCLC, ORR is approximately 20% with a large proportion of patients not responding to these therapies [6,7,69]. Furthermore, a small proportion of them developed 'hyperprogression' to ICIs defined as a 'RECIST progression at the first evaluation and as a ≥2-fold increase of the tumor growth rate prior and upon anti-PD-1/PD-L1 therapies' while 'early deaths' within the first 3 months of treatment with ICIs have been reported in about 10% of nonsquamous NSCLC patients included in the CheckMate 057 trial [70][71][72]. New clinical data are confirming the existence of this aggressive disease in a fraction of patients [70], making the identification of predictive biomarkers an urgent challenge for translational lung cancer research ( Figure 2).…”

PD-L1 as a biomarker in NSCLC: challenges and future directions

“…However, CM 057 (non-squamous NSCLC) did show a predictive association between PD-L1 expression and OS benefit with nivolumab compared to chemotherapy: P=0.06 at 1% PD-L1 expression, P<0.001 for 5% and 10% expression levels. Intriguingly, in an analysis of early survival for patients in CM 057, Peters and colleagues showed that patients with poor prognostic factors (<3 months since last treatment, progressive disease as best response to prior treatment, ECOG performance status of 1), in conjunction with low or no PD-L1 expression, were at a higher risk of death within the first 3 months of treatment with nivolumab compared to docetaxel, partly explaining the non-proportional hazards seen in this study (OS curves crossed ~7 months) (13). However, most patients treated with nivolumab with low or no PD-L1 expression did not die within the first 3 months and many had durable treatment benefit with nivolumab, a finding that suggests PD-L1 score alone is insufficient for patient selection for nivolumab.…”