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ORAL 31 - PD1 Axis Inhibition (ID 143)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
ORAL31.06 - An Exploratory Responder Analysis of Best RECIST Response and Survival in Patients with Metastatic Squamous NSCLC Treated with Nivolumab (ID 1701)
16:45 - 18:15 | Author(s): S. Tang
New therapeutic modalities in metastatic squamous non-small cell lung cancer (SQ NSCLC) focus on targeting pathways (programmed cell death 1 [PD-1]) involved in inhibiting anti-tumor T cell responses leading to tumor evasion. Nivolumab, an anti-PD-1 monoclonal antibody, blocks T cell inhibitory signal pathways by preventing engagement of PD-1. On March 4, 2015, FDA approved nivolumab for the treatment of patients with metastatic SQ NSCLC with progression on or after platinum-based doublet chemotherapy. The approval was based on a randomized study (CA209017) demonstrating a large magnitude of improvement in overall survival (OS) and was supported by single arm study (CA209063) demonstrating a 15% objective response rate (ORR), which appeared to be durable. We conducted a retrospective exploratory responder analysis to evaluate the association between response and OS in study CA209063. Figure 1
CA209063 was a multicenter, multinational, single-arm, open-label study in patients with SQ NSCLC who previously received at least two lines of systemic therapies. Patients (n=117) received nivolumab 3 mg/kg as an intravenous (IV) infusion every 2 weeks until progressive disease (PD) or toxicity; treatment past PD was allowed if certain “clinical benefit” criteria were met. Response was defined as a partial response (PR) or complete response (CR) as determined by a blinded independent review committee (IRC) utilizing the Response Evaluation Criteria In Solid Tumors (RECIST) criteria (98 of 117 were evaluable). Responders were categorized into the following groups: A CR or PR, stable disease (SD), PD with continuation of treatment, and PD with discontinuation of treatment. A sensitivity landmark-based analysis was performed to exclude timing of response evaluation bias (Anderson et al, 1983).
The exploratory responder analysis showed that patients who achieved a best response of CR or PR had the longest survival with anti-PD1 therapy, followed by patients who either achieved a best response of SD or PD with continuation of treatment beyond RECIST progression. Patients whose best response was PD and no treatment beyond progression had poor survival (figure 1). The Landmark time-based sensitivity analysis at 3.5 months (median time to response) also suggested that responders had longer survival than non-responders.
Our analysis suggests that patients with NSCLC who respond are likely to derive the most clinical benefit from anti-PD1 therapy. However, given the exploratory retrospective nature of this analysis, results should be interpreted cautiously. Further development of predictive biomarkers to identify patients most likely to respond is necessary.
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