Abstract 967P
Background
Although PD-1 blockade represents a major breakthrough in non-small cell lung cancer (NSCLC) treatment, primary/acquired resistance frequently occurs. Fasting-mimicking conditions increase tumor immunogenicity and sensitize lung tumors to PD-1 blockade by reducing insulin-like growth factor 1 (IGF-1). We studied whether the time of anti-PD-1 infusion, which might reflect fasting conditions, may correlate with clinical outcomes in NSCLC patients.
Methods
NSCLC patients from two Spanish academic institutions treated with anti-PD-1 were categorized in two groups according to the time of anti-PD-1 infusion (A: patients who received at least one of the first four treatment cycles before 12 pm; B: patients receiving all first four cycles after 12 pm). On treatment iRECIST assessment was performed every 8-12 weeks. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints were disease control rate (DCR) at the first radiologic evaluation and correlation between circulating levels of IGF-1 and related proteins and clinical outcomes.
Results
Of the 197 patients enrolled (72.1% males; median follow up of 9.6 months), 104 (52.8%) were assigned to group A and 93 to group B (47.2%). Most patients presented non-squamous cell carcinoma (72.6%) and received anti-PD-1 monotherapy (N=166 patients; 84.3%). The remaining patients (N=31) received anti-PD-1 plus chemotherapy combinations. In the univariate analysis, median PFS was 6.5 months in group A and 3.2 months in group B (p=0.066). Median OS was 16.1 and 7.4 months, respectively (p=0.003). In a multivariate model adjusted by age, gender, histology, treating institution and treatment line, HR for PFS was 0.418 (95% CI 0.275-0.634; p<0.001) and HR for OS was 0.545 (95% CI = 0.352–0.845; p=0.007). No significant differences in DCR at first evaluation were observed between groups. Circulating levels of IGF-1-related factors involved are being currently analyzed and will be presented at the meeting.
Conclusions
Anti-PD-1 administration before 12 pm significantly improved PFS and OS in NSCLC patients suggesting a potential correlation with fasting. Circulating levels of metabolic factors involved might explain these results.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.