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P. Vigneri
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P3.02c - Poster Session with Presenters Present (ID 472)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02c-090 - The Role of ERCC-1 Polymorphisms as Predictive Biomarker of Response to Nivolumab in Advanced NSCLC (ID 6154)
14:30 - 14:30 | Author(s): P. Vigneri
- Abstract
Background:
Programmed death1 (PD-1) pathway is a negative feedback system limiting T cell activity in normal tissues,frequently upregulated by tumors to escape from immune destruction. Blockade of this pathway with anti PD-1 antibodies has shown significant clinical activity in different cancer types; nevertheless it is still unclear why some patients respond to immunotherapies while others do not. Recently it was observed that cancers with higher somatic mutation burden, as tumors with genome instability due to DNA repair defects, develop more elevated anti PD-1 induced neoantigen specific T cell response which results into increased susceptibility to PD-1 blockade. We hypothesize that NSCLCs with polymorphisms of ERCC-1 gene (encoding for a key enzyme of DNA nucleotide excision repair pathway) may be more responsive to PD-1 blockade than ERCC-1 proficient NSCLCs as result of higher rates of mutation due to their genetic instability.
Methods:
We evalueted the rs11615, rs3212986 and rs2298881 ERCC-1 polymorphisms by pyrosequencing analysis on tumor DNA of stage IV previously treated NSCLC patients receiving nivolumab 3 mg/kg q2w.
Results:
Between Jul 8, 2015 and Jan 19, 2016, we enrolled 24 NSCLC patients to receive nivolumab. Patient characteristics were as follows: M/F =18/6; median age (range) = 65 (49-80); ECOG PS, 0/1 = 22/2; sqNSCLC/non sq NSCLC = 6/18; smokers/nonsmokers/former smokers = 10/2/12; EGFR status, mutant/wildtype/unknown = 2/11/11; median nivolumab cycles delivered (range) = 9 (1-22). No patients presented rs11615 and rs2298881 polymorphisms. 8 patients were positive for the rs3212986 polymorphism. The rate of objective response for the entire population was 25% (95% CI, 10 to 47). The ORR was significantly higher in NSCLC patients positive for rs3212986 polymorphism than wild-type NSCLC patients (62.5% [95% CI, 25 to 92] vs. 6% [95% CI, 0 to 30], P=0.006). Among patients positive for rs3212986 polymorphism, median PFS was not reached. In contrast wild-type patients presented a median PFS of 2.0 months (0.21; 95% CI, 0.07 to 0.58; P= 0.004).
Conclusion:
This study suggested that rs3212986 ERCC-1 polymorphism is associated with a higher RR and PFS in advanced NSCLC patients treated with nivolumab. Confirmation of these results in a validation set is ongoing.
