Virtual Library
Start Your Search
Andrea Ardizzoni
Author of
-
+
MA03 - Clinomics and Genomics (ID 119)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:Heather A Wakelee, Wilfried Ernst Erich Eberhardt
- Coordinates: 9/08/2019, 10:30 - 12:00, Colorado Springs (1994)
-
+
MA03.03 - CEA and CYFRA 21-1 as Prognostic Biomarkers of Benefit from Nivolumab and as a Tool in Treatment Monitoring in Advanced NSCLC (Now Available) (ID 1370)
10:30 - 12:00 | Author(s): Andrea Ardizzoni
- Abstract
- Presentation
Background
To assess the role of pre-therapy levels of Carcinoembryonic antigen (CEA) and Cytokeratin-19 Fragments (CYFRA 21-1) as prognostic marker in advanced NSCLC patients treated with nivolumab, and their change as an early predictor of treatment outcome.
Method
This is a retrospective cohort study including all patients with stage IIIB – IV NSCLC who received nivolumab after first-line chemotherapy in 2 Italian institutions. Median Overall Survival (OS), Overall Response Rate (ORR), Disease Control Rate (DCR) and Time to Treatment Failure (TTF) were chosen as endpoints.
Result
100 patients were included. Cyfra 21-1 > ULN resulted correlated with OS (FIG.1A) both in univariate (HR 2.77, 95% CI 1.53 – 5.30, p 0.001) and multivariate analysis (HR 2.72, 95% CI 1.44 – 5.16, p 0.002). The only other factor correlated with OS in multivariate was ECOG PS (0-1 vs 2) (HR 5.46, 95% CI 3.07 – 9.91, p< 0.001) (Table 1).
ECOG PS (0-1 vs 2) and CYFRA 21-1 (≤ 3.5 vs > 3.5) where combined to create a prognostic score (FIG.1B). Median OS was 23.9 months for patients without risk factors, 6.3 months with one (HR 2.75, 95% CI 1.40 – 5.40 p 0.003) and 1.3 months with 2 risk factors (HR 14.50, 95% CI 6.35 – 33.09, p< 0.001).
Early 20% reduction after 3rd cycle was correlated with OS for CEA, HR 0.05 (95% CI 0.01–0.41), p 0,003 and borderline for CYFRA 21-1, HR 0.29 (95% CI 0.09 – 1.01), p 0.052. (FIG.1C-1D).
ConclusionUnivariate
Multivariate
Covariate
HR (95% CI)
P value
HR (95%CI)
P value
ECOG PS 2 vs 0-1
5.40 (3.21 – 9.09)
< 0.001
5.46 (3.07 – 9.91)
< 0.001
Cyfra > vs ≤ ULN
2.77 (1.53 – 5.03)
0.001
2.72 (1.44 – 5.16)
0.002
Liver metastasis yes vs no
2.19 (1.26 – 3.78)
0.005
0.102
Neutrophil/lymphocyte ratio ≥ 4 vs < 4
1.99 (1.23 – 3.20)
0.005
0.105
KRAS mutated vs wild type*
0.39 (0.21 – 0.74 )
0.004
0.262
Bone metastasis yes vs no
1.75 (1.10 – 2.79)
0.018
0.362
Response to previous therapy yes vs no
0.51 (0.29 – 0.91)
0.023
0.376
CEA > vs ≤ ULN
1.41 (0.88 – 2-25)
0.150
0.418
Stage IV vs IIIB
1.63 (0.75 – 3.54)
0.22
0.449
Squamous vs non squamous
0.79 (0.48 – 1.28)
0.334
0.689
Smoker vs never smoker
0.88 (0.65 – 1.18)
0.386
0.694
Second-line vs third or more
0.94 (0.60 – 1.47)
0.77
0.843
Brain metastasis yes vs no
1.16 (0.66 – 2.04)
0.603
0.594
Our data suggests that Cyfra 21-1 pre-therapy assessment, both alone and in combination with other factors in a prognostic/predictive score, may provide clinicians with further information on the prognosis of patients treated with nivolumab.
CEA and CYFRA 21-1 repeated measures could be useful as an early surrogate marker of clinical benefit.
Further analysis are warranted to confirm these findings.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
P2.01 - Advanced NSCLC (ID 159)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
-
+
P2.01-02 - CANOPY-A: A Phase 3 Study of Canakinumab as Adjuvant Therapy in Patients with Surgically Resected NSCLC (ID 1569)
10:15 - 18:15 | Author(s): Andrea Ardizzoni
- Abstract
Background
Overexpression of interleukin (IL)-1β has been described in solid tumors, including lung. IL-1β can promote angiogenesis, tumor invasiveness, and induces tumor-associated immunosuppression through myeloid-derived suppressor cell (MDSC) accumulation in tumors. Pre-clinical data has shown that IL-1β inhibition reduced tumor growth, by limiting pro-tumorigenic inflammation and polarization of MDSCs into M1 phenotype. Canakinumab is a human monoclonal antibody with high affinity and specificity for IL-1β. Recently, it was found that canakinumab was associated with a significant and dose-dependent reduction in incidence and mortality from lung cancer based on CANTOS study.
Method
CANOPY-A (NCT03447769) is a phase III, randomized, double-blind, placebo-controlled study designed to evaluate efficacy and safety of adjuvant canakinumab versus placebo in patients with surgically resected NSCLC. This trial will enroll adult patients, with completely resected (R0) AJCC/UICC v.8 stages II-IIIA and IIIB (T >5 cm and N2) NSCLC, who have completed standard-of-care adjuvant treatments, including cisplatin-based chemotherapy and mediastinal radiation therapy (if applicable). Prior treatment with neoadjuvant chemotherapy or neoadjuvant radiotherapy is not permitted. Approximately 1500 patients will be randomized 1:1 to receive canakinumab (200 mg Q3W, s.c) or placebo (Q3W, s.c.) for 18 cycles or until disease recurrence, unacceptable toxicity, treatment discontinuation at the discretion of the investigator or patient, death, or loss to follow-up. Randomization will be stratified by AJCC/UICC v.8 stage, tumor histology, and region. The primary objective is disease-free survival, per investigator assessment. Secondary objectives include overall survival (key secondary objective), lung cancer-specific survival, safety, pharmacokinetics and immunogenicity of canakinumab, and patient-reported outcomes. Enrollment is ongoing.CANOPY-A (NCT03447769) is a phase III, randomized, double-blind, placebo-controlled study designed to evaluate efficacy and safety of adjuvant canakinumab versus placebo in patients with surgically resected NSCLC. This trial will enroll adult patients, with completely resected (R0) AJCC/UICC v.8 stages II-IIIA and IIIB (T >5 cm and N2) NSCLC, who have completed standard-of-care adjuvant treatments, including cisplatin-based chemotherapy and mediastinal radiation therapy (if applicable). Prior treatment with neoadjuvant chemotherapy or neoadjuvant radiotherapy is not permitted. Approximately 1500 patients will be randomized 1:1 to receive canakinumab (200 mg Q3W, s.c) or placebo (Q3W, s.c.) for 18 cycles or until disease recurrence, unacceptable toxicity, treatment discontinuation at the discretion of the investigator or patient, death, or loss to follow-up. Randomization will be stratified by AJCC/UICC v.8 stage, tumor histology, and region. The primary objective is disease-free survival, per investigator assessment. Secondary objectives include overall survival (key secondary objective), lung cancer-specific survival, safety, pharmacokinetics and immunogenicity of canakinumab, and patient-reported outcomes. Enrollment is ongoing.
Result
Section not applicable
Conclusion
Section not applicable