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Alona Zer
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OA11 - Decomplexifying Molecular Targets, Immunotherapy and Treatment Settings in the Real World (ID 137)
- Event: WCLC 2019
- Type: Oral Session
- Track: Treatment in the Real World - Support, Survivorship, Systems Research
- Presentations: 1
- Now Available
- Moderators:Kumar Prabhash, Jyoti D Patel
- Coordinates: 9/09/2019, 14:00 - 15:30, Interlaken (1988)
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OA11.06 - Alternative Nivolumab (N) Duration and Scheduling in Advanced Non-Small Cell Lung Cancer (aNSCLC): Real-Life Data (Now Available) (ID 1921)
14:00 - 15:30 | Author(s): Alona Zer
- Abstract
- Presentation
Background
Little is known regarding the optimal scheduling and treatment (Tx) duration of N in aNSCLC. Stopping N after 1 year of Tx negatively affects outcomes.
Method
45 consecutive aNSCLC patients (pts) receiving N for ≥2 years (y) were identified in the electronic databases of 4 Israeli cancer centers. These were divided into Groups A (N continued for >2y at a dose 3mg/kg q2w/240mg q2w; n-21), B (N continued for >2y at a dose 3mg/kg q3w-q8w/480mg q4w; n-17), and C (N stopped at 2y for reason other than progressive disease or intolerable toxicity; n-7). PFS (RECIST 1.1) and safety since 2y after N initiation were assessed.
Result
Baseline, treatment characteristics and outcomes are presented in the Table and the Picture. Allocation to Group B and C was associated with HR for PFS-2.4 (95%CI, 0.3-18.8, p-0.4) and HR for PFS-3.3 (95%CI, 0.3-30.9, p-0.3), respectively. After 2y since N initiation, new N-related toxicity developed in 24%, 18%, and 28% of pts in Groups A, B, and C, respectively (p-NS).
Conclusion
A trend for worse outcomes was observed with alternative N scheduling/N quitting 2y after initiation. So far, continuing N at a standard dose until disease progression/ intolerable toxicity remains the standard treatment option.
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-70 - Dominant Circulating Myeloid Populations Are Associated with Poor Response in NSCLC Treated with 1st Line PD-1 Monotherapy (Now Available) (ID 2295)
09:45 - 18:00 | Author(s): Alona Zer
- Abstract
Background
Immune subpopulations within the tumor microenvironment (TME) play a central role in determining response to checkpoint inhibitors. Myeloid derived suppressor cells (MDSC), a heterogeneous population of immature myeloid cells, have a predominantly immunosuppressive role by stimulating T regulatory cells. We hypothesize that elevated myeloid-to-lymphocyte measures in the peripheral blood predict for greater numbers of myeloid derived suppressor cells in the TME and worse outcomes.
Method
We identified all advanced NSCLC patients treated with immunotherapy between 2010-2019 at the Princess Margaret Cancer Center. Patients who received first line monotherapy with a PD-1 inhibitor were reviewed for clinical information including age, sex, histology, stage, smoking status, ethnicity, PD-L1 expression and tumor genotype. Myeloid cells lines analyzed included neutrophils, monocytes and platelets, expressed as ratios to peripheral lymphocytes. Multivariate analyses were conducted using the cox and logistic regression models to adjust for confounders.
Result
We identified 75 patients who were eligible for analysis. Disproportionate increases in the different myeloid cell types were highly correlated with each other (all Pearson’s rho>0.8) and the neutrophil to lymphocyte ratio (NLR) was selected as representative. A high NLR (>5) was associated with shorter time-to-treatment-failure (median TTF 9.7 vs 29.4 months) that remained significant after adjusting for confounders including PD-L1 and presence of liver metastases (p=0.004). High NLR was also an independent predictor of poor OS (median 11.3 vs 56.8 months, HR 3.02, p=0.04). Although NLR was not predictive of radiographic response, there was a trend to association with a rapidly progressive phenotype defined by primary progressive disease and a duration of therapy ≤2 months (p=0.06). Other predictive factors included the presence of liver metastases, which was associated with a worse OS (HR3.37 p=0.05) but not TTF (p=0.14). An association was also seen between NLR and liver metastases (mean NLR 6.6 vs 25.2 in the absence and presence of liver metastases respectively, p<0.001).
Conclusion
A disproportionate increase in peripheral immune myeloid populations may represent a systemic, myeloid-driven, immunosuppressive state that is significantly associated with primary refractory disease, rapid progression, and poor survival. A subset of about 50 patients with biobanked tissue are presently being analyzed using multiplex immunofluorescence to assess for MDSCs in the TME to correlate with peripheral blood findings.
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P2.06 - Mesothelioma (ID 170)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Mesothelioma
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.06-14 - BAP1 Mutant Malignant Pleural Mesothelioma (MPM): Outcomes with Chemotherapy, ICPi and PARPi (Now Available) (ID 1244)
10:15 - 18:15 | Author(s): Alona Zer
- Abstract
Background
Little is known regarding the outcomes of systemic treatments (Tx) in BAP1 altered MPM.
Method
45 patients (pts) with advanced MPM (Group A: 8 MPM with a BAP1 inactivating mutation/copy number loss (FoundationOne CDx/TEMPUSxT), selected from the electronic databases (eD) of 4 Israeli cancer centers (ICC); Group B: 37 consecutive (years 2016-2018) MPM without a BAP1 alteration/not tested, selected from the eD of 2 ICC) were analyzed for ORR, PFS (mRECIST 1.1) and OS with platinum/pemetrexed+/-bevacizumab/nintedanib (CT, n-28), immune check-point inhibitors (ICPi, n-16) and poly (ADP-ribose) polymerase inhibitors (PARPi, n-4). OS since diagnosis (OSDx) was assessed.
Result
Pt and Tx characteristics are presented in the Table. There were no differences in ORR, mPFS or mOS with CT between the Groups: ORR-50% in both Groups, mPFS-9.1mo (95%CI, 1.2-16.1) vs 9.2mo (95%CI, 2.9-17.8) (log-rank-0.01, p-0.9), mOS-NR (95%CI, 6.6-NR) vs 18.5mo (95%CI, 5.4-46.3) (log-rank-1.1, p-0.3), in Groups A and B, respectively. There were no differences in ORR, mPFS or mOS with ICPi between the Groups: ORR- 33% vs 50% (p>0.5), mPFS-2.5mo (95%CI, 1.4-3.7) vs 3.0mo (95%CI, 0.3-10.5) (log-rank-0.5, p-0.4), mOS-NR (95%CI, 4.0-NR) vs 5.8mo (95%CI, 0.3-13.2) (log-rank-0.1, p-0.7), in Groups A and B, respectively. In Group A, no responses were seen with PARPi; PFS with PARPi was 1.8mo (95%CI, 1.8-1.9). OSDx was NR (95%CI, 9.7-NR) vs 19.5mo (95%CI, 9.7-82.2) in Groups A and B, respectively (log-rank-1.6, p-0.2). In the univariate analysis, sex (p-0.04), histology (p-0.002), ECOG PS (p-0.03), but not BAP1 mutation (p-0.3) correlated with OSDx.
Conclusion
Outcomes with CT and ICPi in BAP1 mutant MPM are similar to non-selected MPM. No responses were seen so far with PARPi. According to our data, presence of BAP1 mutation does not affect OS. Additional follow-up is needed.
