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P1.06 - Poster Session with Presenters Present (ID 458)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.06-043 - A Study to Select Rational Therapeutics in Subjects with Advanced Malignancies (WINTHER) - The Sheba Experience in Lung Cancer Patients (ID 6414)
14:30 - 14:30 | Author(s): J. Bar
- Abstract
Background:
Patient-tailored therapy based on tumor genomics is a promising tool in cancer therapy. However, in current practice it is limited to 30-40% of the patients whose tumor harbor actionable DNA mutations or amplifications
Methods:
: WINTHER is an open label non-randomized clinical trial developed by the WIN consortium to provide a rational personalized therapeutic choice to all (100 %) enrolled patients, irrespective of the type of genomic events. The study includes patients with metastatic cancer who progressed on at least one line of therapy. Matched tumor and normal tissue biopsies are collected from each patient and analyzed by next-generation-sequencing for known oncogenic driver aberrations (Foundation Medicine) or by functional genomics utilizing a prediction model of efficacy developed at Ben Gurion University. Based on these results study leaders from all centers make therapy decisions. The study aim is to compare progression free survival rates between the previous treatment line and the study drug/s. Patient accrual began in 2013 in four international cancer centers. The following is a description of the experience at Sheba Medical Center., specifically focusing on a large sub-population of lung cancer patients.
Results:
Fifty six patients were screened and biopsied for the study. The majority of patients were diagnosed with lung cancers (52%), with a diverse representation of other malignancies including breast (16%), renal (9%), colon (9%), sarcoma, bladder and head and neck. Successful biopsies yielding sufficient material for genomic analyses were achieved in 35 subjects (63%). Lung biopsy success rates were 75% and 60% respectively for normal and tumor specimens. To date, 11 lung cancer patients were treated with a variety of chemotherapy (1) or biologic agents (11) based on study recommendations while 3 have yet to progress on previous therapy. Targeted genomic alterations included EGFR (3), RET (2), KRAS (2), ALK (1), ErbB2 (1), ErbB3 (1), BRAF (1). We observed a clinical benefit rate (CBR) of 55% (6/11) with 1 subject achieving compete response (CR), 2 partial responses (PR) and 3 stable disease (SD). Subjects recruited during the second year of the study, compared to the first year had a reduced biopsy failure rate, were more likely to receive treatment and achieved an increased clinical benefit.
Conclusion:
The proposed strategy for tumor genomic analysis based on the comparison of matched tumor and normal biopsies is acceptable and feasible. The experience of the multidisciplinary team is an important contributor to the program’s success.
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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-053 - Clinical and Plasma Biomarkers for Disease Control with Nivolumab Treatment for Advanced Non-Small Cell Lung Cancer (NSCLC) (ID 4715)
14:30 - 14:30 | Author(s): J. Bar
- Abstract
Background:
Anti-PD1 antibodies have become the treatment of choice for most advanced NSCLC patients after failure of first line platinum-based chemotherapy. Responses are seen in roughly 20% of treated patients. PDL1 expression level and mutational burden might be predictive factors but are not always available and their predictive accuracy is limited. Predictive biomarkers are urgently needed. We hypothesized that clinical data and baseline blood tests might be predictive for benefit from nivolumab.
Methods:
A chart review was performed of patients with advanced NSCLC who received at least one cycle of nivolumab, at one of three cancer centers during 2015-2016. Additional inclusion criteria were: available baseline clinical data, evaluation of response and availability of blood test results. Blood test results collected were: Absolute Lymphocyte Count (ALC), Absolute Neutrophil Count (ANC), White Blood Cells (WBC), Hemoglobin (Hb), Platelets (PLT), Albumin (ALB), Lactate Dehydrogenase (LDH). Blood test results were collected at baseline and before the second and third treatment. Disease control (DC) was defined as any tumor shrinkage, or stable disease for at least 6 months, as assessed by the treating physician by computerized tomography scans. Patients with DC were compared with patients with progressive disease (PD, patients progressing within the first 6 months). Uni- and multivariate regression analyses were performed using Stata (version 11.2, StataCorp).
Results:
A total of 70 patients treated with nivolumab were included, median age 67 years, 66% males, 27% with DC. DC patients compared to PD patients were younger (61.6 vs 69.3 yr, p<0.001), more females (42% vs 27%, p<0.05), and had a lower baseline WBC (6.9 vs 9.2 K/microL, p<0.05). The difference in WBC between DC and PD patients increased during treatment (2.3 K/microL at baseline, 2.6 prior to third treatment). Lower baseline neutrophil count was associated with DC (p=0.02). Neither performance status nor LDH predicted outcome on uni-variate analysis. On multivariate analysis age (p=0.050) and baseline WBC (p=0.02) were associated with outcome. Patients less than 67 years of age with baseline WBC<8.04 K/microL (n=18) had DC rate of 50%, while DC rate was 4% in patients 67 years or more, with WBC >=8.04 K/microL (n=23).
Conclusion:
We have identified clinical biomarkers (age and baseline WBC) that are associated with DC under nivolumab treatment. Validation on an independent data set is warranted. The association of a low peripheral WBC/ANC with increased response rate raises the possibility that acute inflammatory responses are counteractive to anti-PD1 therapy.
