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M.M. Aiello
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P1.03 - Poster Session with Presenters Present (ID 455)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Radiology/Staging/Screening
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.03-015 - Assessment of Response of FDG-PET Using Total Lesion Glycolysis (TLG) in NSCLC Patients Treated with Nivolumab: Results of a Pilot Study (ID 4895)
14:30 - 14:30 | Author(s): M.M. Aiello
- Abstract
Background:
Recent studies using FDG-PET measure the total volumes of the FDG-avid lesions to represent whole-body total metabolic tumor volume (MTV) demonstrating prognostic significance in NSCLC. Total lesion glycolysis (TLG) is the product of mean SUV and MTV and studies have shown the usefulness of TLG for evaluating treatment response. We decide to preliminarily explore the role of TLG, which combines the volumetric and metabolic information of the FDG-PET, as an early predictor of response to nivolumab in NSCLC patients and to determine whether in these patients TLG could provide a better evaluation of response when compared to RECIST.
Methods:
Between September 2015 and April 2016, we enrolled 15 previously treated advanced NSCLC patients to receive nivolumab 3 mg/kg q2w. The CT-scan and FDG-PET evaluation were performed before starting therapy and after 8 weeks (early evaluation). We compared responses assessed by CT-scan and FDG-PET at 8 weeks according to RECIST 1.1 and TLG parameter respectively. We also performed a CT-scan at 12 weeks to confirm or refute the results of the assessement at 8 weeks.
Results:
There are no standard cut-offs for the TLG parameter. A ROC curve was used to obtain thresholds for the TLG criteria. The ROC study suggested a TLG value between -76% and +76% to define an SD. We considered a TLG value above +76% to define a PD, while a TLG inferior to -76% was necessary to define a PR. In one patient the evaluation at 8 weeks according to TLG criteria showed PD. The same patient presented SD according to RECIST assessed by CT-scan at 8 weeks. For this patient CT-scan at 12 weeks confirmed PD. In this case the TLG of the FDG-PET early identified the patient's progression better than CT-scan. In other two patients, TLG criteria assessed at 8 weeks identified a PR in contrast with SD according to RECIST assessed by CT-scan at 8 weeks. CT-scan at 12 weeks confirmed PRs for both these patients. Even in this two cases the evaluation of TLG by FDG-PET early recognized patient's responses better than CT-scan. For the remaining 12 patients no differences in terms of responses were observed between RECIST and TLG criteria at 8 weeks when compared to RECIST assessed by CT-scan at 12 weeks.
Conclusion:
These preliminary results from this small study suggest that TLG criteria could provide an early identification of response to nivolumab in NSCLC patients.
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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): M.M. Aiello
- 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.
