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Jonathan W Riess
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OA11 - Thymic and Other Thoracic Tumours: Targeted Therapies, Biomarkers and Neo/Adjuvant Radiotherapy (ID 919)
- Event: WCLC 2018
- Type: Oral Abstract Session
- Track: Thymoma/Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 13:30 - 15:00, Room 205 BD
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OA11.02 - A Population-Based Study of Incidence and Survival Trends of 1,588 Thymic Malignancies: Results from the California Cancer Registry (ID 12459)
13:40 - 13:50 | Author(s): Jonathan W Riess
- Abstract
- Presentation
Background
Thymic malignancies (TM) are rare with sparse population-based epidemiologic literature. According to data collected by the National Cancer Institute from 1973 to 2006, the incidence of thymomas is 0.13 per 100,000 person-years in the United States.
a9ded1e5ce5d75814730bb4caaf49419 Method
We used data from the California Cancer Registry (CCR), a comprehensive population-based state registry to examine TM incidence and survival trends in California from 1988 to 2015. Cases were specified by site (thymus), histology (thymic carcinoma and thymoma), and behavior (malignant). Primary endpoints were cause-specific survival (CSS) and overall survival (OS). Age-adjusted incidence rates were calculated in SEER*Stat, and Joinpoint regression was used to analyze incidence trends. Hazard ratios (HR) for CSS and OS were calculated using a Cox proportional hazards regression model controlling for relevant baseline variables including age, gender, stage, and year of diagnosis, among others.
4c3880bb027f159e801041b1021e88e8 Result
We identified 1,588 TM cases in California from 1988 to 2015 with an annual percent increase of 2.08% (95% CI: 1.3%, 2.9%; p < 0.0001). The incidence of TM in 2015 was 0.277 per 100,000. Thymic carcinoma histology was associated with worse CSS across all stages, including localized (HR 7.56, 95% CI 1.44, 39.78), regional (HR 4.23, 95% CI 2.55, 7.01), and remote (HR 2.09, 95% CI 1.37, 3.19) disease. Compared to no treatment, surgery with or without radiation was associated with improved CSS in localized (surgery: HR 0.05 (95% CI 0.01 to 0.35), surgery + radiation: HR 0.12 (95% CI 0.02 to 0.84)) and regional disease (surgery: HR 0.11 (95% CI 0.04 to 0.29), surgery + radiation: HR 0.15 (95% CI 0.06 to 0.36)). Chemotherapy and radiation was also associated with improved CSS in regional disease (HR=0.22 (95% CI 0.07 to 0.63) and remote disease (5.16 (0.37, 71.94)), though the latter was not statistically significant.
8eea62084ca7e541d918e823422bd82e Conclusion
This is a population-based study of TMs from the CCR that identifies baseline variables significantly associated with CSS. TM incidence appears to be increasing over time. Advanced stage and thymic carcinoma were found to be associated with worsened CSS, which is consistent with previous studies. Treatment incorporating surgery was associated with improved CSS in local and regional disease, as was chemoradiation in regional disease. Improvement in CSS trended towards significance in patients with remote thymic neoplasms treated with chemoradiation. These findings provide a more contemporary database for future TM outcomes research.
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P1.04 - Immunooncology (Not CME Accredited Session) (ID 936)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.04-09 - Immunomodulatory Effects of Afatinib and Pembrolizumab in EGFR-Mutant NSCLC with Progression on Prior EGFR-TKI (ID 12185)
16:45 - 18:00 | Presenting Author(s): Jonathan W Riess
- Abstract
Background
EGFR-mutant NSCLC is less responsive to single agent PD-1 blockade than smoking associated NSCLC. Preclinical models suggest EGFR-TKI can render a more immunocompetent tumor microenvironment. This study examined the immunomodulatory effects of combination second generation EGFR-TKI and PD-1 antibody.
a9ded1e5ce5d75814730bb4caaf49419 Method
In this phase 1 dose de-escalation study, patients were treated with afatinib 40 mg oral daily and pembrolizumab 200 mg IV q21day. Key Eligibility: advanced EGFR-mutant NSCLC with progression (PD) on prior EGFR-TKI, age≥18, ECOG PS≤1, acceptable organ function, no significant autoimmune diseases, measurable disease and controlled brain metastases. Tissue biopsy performed baseline and week 5-6 on treatment for PD-L1 IHC (22C3) and quantitative immunofluorescence for immune cell subsets and next-generation sequencing. Blood at baseline and at serial on-treatment timepoints were collected for ctRNA of PD-L1, EGFR, HER2 and MET; changes in circulating immune cell subsets, T-Cell repertoire and cytokine levels were evaluated by flow cytometry and Luminex.
4c3880bb027f159e801041b1021e88e8 Result
No DLTs were observed in the first 6 patients and the 10 patient expansion cohort proceeded at afatinib 40 mg daily and pembrolizumab 200 mg IV q21day. Eleven patients enrolled to date. Key molecular and pathologic characteristics: adenocarcinoma 9, neuroendocrine 1, squamous 1. EGFR-TKI resistance mechanism: EGFR-T790M 4, EGFR-T790M/C797S 1, HER2 amp 1, MET 2, Her2 amp+neuroendocrine differentiation 1, unknown 2. Five patients had prior second line osimertinib. Three (27%) patients had immune related AEs (G2 adrenal insufficiency, G2 nephritis, G3 colitis). Nine patients were evaluable for response: (1 PR, 7 SD ((6/7) with tumor reduction <30%)). The responding patient had squamous histology tumor, prior PD on erlotinib, and PFS of 11 months with PD-L1 (22C3) TPS 40% and PD-L1 and PD-L2 amplification. Treatment with afatinib and pembrolizumab induced systemic immune changes including trend for increased soluble IDO, MIG, TIM3, IP-10, LAG3, PD-L1 and PD-L2 and decreased IFN-gamma. ctRNA for EGFR and PD-L1 were detected in 7/7 and 6/7 patients, respectively, with dynamic changes in allele frequency of EGFR and PD-L1 observed. Baseline PD-L1 (22C3) TPS ranged from 0% to 75% expression. Four patients had repeat biopsy and in paired samples analyzed PD-L1 (22C3) expression decreased in the stroma.
8eea62084ca7e541d918e823422bd82e Conclusion
Immunomodulatory effects of afatinib with pembrolizumab were noted in the tumor microenvironment and peripheral blood. Only modest clinical activity has been observed thus far in patients with PD on prior EGFR-TKI. Genomic and immune-profiling is feasible in EGFR-mutant NSCLC and may identify EGFR-mutant NSCLC patients who may respond or lack benefit to PD-1 blockade.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P3.13 - Targeted Therapy (Not CME Accredited Session) (ID 979)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.13-26 - Outcomes of Patients with Metastatic Lung Cancer Presented in a Multidisciplinary Molecular Tumor Board (ID 12838)
12:00 - 13:30 | Author(s): Jonathan W Riess
- Abstract
Background
With the adoption of broad genomic profiling, interpretation of genomic data in NSCLC has become increasingly complex. Approved targeted therapies against oncogenic driver mutations have improved clinical outcomes for patients whose lung cancers harbor these genomic alterations. However, for other patients, the benefit of broad genomic sequencing is not fully proven. Multidisciplinary molecular tumor boards (MTB) may improve clinical outcomes by appropriately matching targeted treatments.
a9ded1e5ce5d75814730bb4caaf49419 Method
We retrospectively reviewed clinical, pathologic, and molecular data of metastatic lung cancer patients presented at the UC Davis MTB from January 2016 through May 2017. Genomic alterations were identified by hybrid capture-based comprehensive genomic profiling to a median coverage depth of >500X for 315 cancer-related genes (FoundationOne®).
4c3880bb027f159e801041b1021e88e8 Result
Out of 48 patients presented, 19 (39.6%) had lung cancer. Fourteen patients (73.7%) had adenocarcinoma, 1 SCLC, 1 squamous, 2 neuroendocrine, and 1 mixed histology. Seventeen patients were available for follow-up.
Median number of prior treatments was 2 (range: 0-7) and median number of prior targeted therapies was 2 (range: 0-5). On average, each tumor sample had 5.3 genomic alterations (range 2 – 14). Every sample had ³1 actionable mutation, in that matched targeted therapy was available in the form of an FDA-approved drug for NSCLC, FDA-approved drug in another tumor type, or genomically informed clinical trial. Tumors harbored an EGFR mutation (N=7), HER2 amplification (N=2), BRAF V600E (N=2), or mutation in BRCA1 (N=1), KIT (N=1), or PTCH1 (N=1). All 7 patients with an EGFR mutation had previously received EGFR-targeted therapy, six with progressive disease (PD) on prior EGFR-TKI.
Thirteen patients (76.5%) received targeted therapy, including FDA-approved therapy for NSCLC (N=4), FDA-approved therapy for another tumor type (N=6), or a genomically informed clinical trial (N=3). The other four patients were either on an immunotherapy clinical trial (N=2) or could not tolerate treatment (N=2). Out of the 13 patients who received targeted therapy, 4 patients had a partial response (31%) (3 EGFR, 1 BRAF V600E), all other patients had stable disease or PD. Median PFS on MTB-selected treatment was 4.8 months (range: 25% 2.2 – 75% 10.7 months).
8eea62084ca7e541d918e823422bd82e Conclusion
MTB at an academic medical center matched a high percentage of patients to either a targeted treatment or clinical trials with targeted therapies or immunotherapy. A subset of patients had clinical benefit to targeted therapies in this pretreated population. Multidisciplinary expertise at MTB can guide treatment for NSCLC, but new targeted treatments are needed to improve clinical outcomes.
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