Virtual Library
Start Your Search
J. Patel
Author of
-
+
P2.03b - Poster Session with Presenters Present (ID 465)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
P2.03b-014 - Atezolizumab in Advanced NSCLC Patients with Baseline Brain Metastases: A Pooled Cohort Safety Analysis (ID 5214)
14:30 - 14:30 | Author(s): J. Patel
- Abstract
Background:
Brain metastases, occurring in 20% to 40% of patients with advanced NSCLC, are associated with poor survival. Atezolizumab (anti-PDL1) inhibits PD-L1/PD-1 signaling and restores tumor-specific T-cell immunity. Clinical benefits have been observed in patients with NSCLC across PD-L1 expression levels following atezolizumab monotherapy, but the safety profile in NSCLC patients with brain metastases has not previously been explored.
Methods:
Pooled safety analyses were conducted in 843 patients who received atezolizumab as 2L+ treatment in 4 studies (PCD4989g: NCT01375842 [N = 76]; BIRCH: NCT02031458 [N = 520]; FIR: NCT01846416 [N = 105]; POPLAR: NCT01903993 [N = 142]). Patients had asymptomatic untreated brain metastases or stable previously treated brain metastases at baseline.
Results:
27 (3%) of 843 patients in the pooled cohort had baseline brain metastases; 23 of whom were previously treated with radiation to the brain. Among the 27 patients, mean age was 60 years, 41% were male, 85% had non-squamous NSCLC, and 70% had received 3L+ therapy. Median number of atezolizumab cycles (21d/cycle) was 4 (range, 1-39). Neurological AEs occurred in 12 (44%) patients with and 229 (28%) patients without baseline brain metastases (Table). The incidence of treatment-related neurological AEs was 4 (15%) in patients with and 77 (9%) in patients without baseline brain metastases, including the most common treatment-related AE of headache in 2 (7%) and 27 (3%) patients, respectively. The most common all-cause AEs in patients with baseline brain metastases were fatigue, nausea, and vomiting (7 [26%] each); 3 (11%) patients developed new brain lesions on study, none during treatment. No treatment discontinuations occurred due to AEs.
Conclusion:
The current analyses indicate that atezolizumab has an acceptable safety profile in patients with NSCLC who have asymptomatic or previously treated stable brain metastases. Further investigation is needed to fully assess the efficacy of atezolizumab in this patient population.Summary of safety data in patients with advanced NSCLC with and without baseline brain metastases following atezolizumab as 2L+ treatment Pooled Cohort (N = 843) Patients Without Baseline Brain Metastases (n = 816) n (%) Patients With Baseline Brain Metastases (n = 27) n (%) Any AE 779 (96%) 26 (96%) Any neurological AE 229 (28%) 12 (44%) Treatment-related AEs 548 (67%) 16 (59%) Treatment-related neurological AEs 77 (9%) 4 (15%) Serious AE 311 (38%) 9 (33%) Serious neurological AEs 21 (3%) 1 (4%) Treatment-related SAEs 78 (10%) 1 (4%) Discontinued treatment due to AE 47 (6%) 0 (0%)
-
+
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)
-
+
P3.02c-058 - In-Depth Molecular Characterization of T Cell Clonal Expansion Induced by Anti-PD1 Therapy in NSCLC (ID 5183)
14:30 - 14:30 | Author(s): J. Patel
- Abstract
Background:
Inhibitors of PD1/PD-L1 checkpoint have been shown to be active among a broad range of cancers including NSCLC. They induce proliferation of T cells within the tumor microenvironment (as revealed by IHC) leading to tumor eradication. There is however lack of detailed molecular characterization of these proliferating T cells including the dynamics of their clonalilty during treatment and its correlation with response, their antigen specificity and the molecular changes induced in the expanded clones at single cell level. Such understanding will serve as a biomarker to detect early response after one dose of therapy, ascertain efficacy (especially when radiological assessments are equivocal) and guide determination of optimal duration of therapy. Furthermore, insight into molecular changes in the proliferating T cell clones induced by these agents at single-cell level will identify the baseline unique characteristics of T cells clones that undergo rapid expansion upon exposure to anti-PD1 therapy, define the molecular mediators of tumor eradication in responders and serve as a foundation for the development of novel treatment strategies for non-responders.
Methods:
We performed next-generation T cell receptor alpha/beta chain sequencing on serially obtained tumor and PBMC samples from 54 NSCLC patients undergoing anti-PD1 therapy. We compared the dynamics of the T cell repertoire in responders versus non-responders within unsorted PBMC and in CD8 positive/negative T cells. We also assessed the expression of key mediators of cytotoxicity and T cell activation/dysfunction in these expanded CD8 T cell clones at single cell level among responders and non-responders.
Results:
We identified concordant early clonal T cell expansion after 1-4 doses of anti-PD1 therapy within the tumor and PBMC of responders. We confirmed these expanded T cell clones to be CD8 positive subgroup of CD3+ T cells in responders and CD8 negative subgroup of CD3+ T cells in non-responders. Furthermore, among responders we found that persistence of the expanded T cell clones for several months while on treatment is associated with durable response. Additional results on antigen specificity and gene expression of the expanded T cell clones in responders versus non-responders will be presented.
Conclusion:
Our results showed that early concordant clonal expansion of a defined population of CD8+ T cells detected both within the tumor and PBMC correlate with response to therapy. We also confirmed that the persistence of these unique T cell clones several months after their initial expansion correlates with durable response.
