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Found 2 Presentations For Request "107P"

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107P - Immune Checkpoint Inhibitor (ICPI) resistance genes STK11 and KEAP1: A comparative Comprehensive Genomic Profiling (CGP) study

Presentation Number
107P
Speakers
  • Brian Alexander (Boston, MA, United States of America)
Date
17.09.2020

Abstract

Background

Inactivating genomic alterations (GA) in the tumor suppressor genes STK11 (STK11mut) and KEAP1 (KEAP1mut) have been linked to ICPI resistance in NSCLC. The following pan-genomic study compares the CGP in both STK11mut and KEAP1mut solid tumors and hematologic malignancies.

Methods

CGP was performed on FFPE samples from 297,209 clinically advanced solid tumors and hematologic malignancies. Tumor mutational burden (TMB) was determined on 0.8 to 1.2 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. PD-L1 expression in tumor cells (Dako 22C3) was measured by IHC.

Results

11,670 (3.9%) and 5,027 (1.7%) featured STK11 and KEAP1 inactivating mutations respectively. Ages were similar; KEAP1mut patients slightly more often male. Inactivation of STK11 was by base substitution in 80% and genomic loss in 20% and for KEAP1 it was 92% base substitutions and 8% genomic loss. NSCLC was the predominant disease type with both SK11mut (65%) and KEAP1mut (55%) cases. 14% of NSCLC featured STK11mut which was most frequent in adenocarcinomas. CUP was the second most frequent tumor type with either STK11mut and KEAP1mut. No other tumor types featured greater than 5% mutation frequencies. Concurrent alteration of the two genes was seen in a greater portion of KEAP1mut than STK11mut (38% vs. 16%, p<0.001). STK11mut had 6.4 GA/tumor; median TMB of 7.4 mut/Mb and 37% PD-L1>1% staining. KEAP1mut had 7.4 GA/tumor, median TMB of 8.8 mut/Mb and 44% PD-L1>1% staining. GA in KRAS, TP53, CDKN2A/B and SMARCA4 were similar in both groups with the SMARCA4 possibly indicating a significant number of CUP cases were actually TTF-1 IHC negative NSCLC.

Conclusions

STK11mut and KEAP1mut occur predominantly in NSCLC with SK11mut more frequent in KEAP1mut cases than vice versa. STK11mut and KEAP1mut tumors are similar in disease type, age, gender, alteration types, frequencies of co-alterations with KRAS, TP53, CDKN2A/B, SMARCA4 and numerous other genes. In addition, STK11mut and KEAP1mut tumors feature biomarkers predictive of ICPI benefit despite the likelihood of resistance and a paucity of targeted therapy opportunities.

Legal entity responsible for the study

Foundation Medicine Inc.

Funding

Foundation Medicine Inc.

Disclosure

B. Alexander: Leadership role, Full/Part-time employment: Foundation Medicine Inc.; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Puma; Research grant/Funding (institution): Eli Lilly. E.S. Sokol: Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc. N.A. Danziger: Full/Part-time employment: Foundation Medicine Inc. D.C. Pavlick: Full/Part-time employment: Foundation Medicine Inc. J. Elvin: Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc. J.K. Killian: Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc. D.I. Lin: Full/Part-time employment: Foundation Medicine Inc. E. Williams: Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc. S. Ramkissoon: Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc. E. Severson: Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc.; Full/Part-time employment: Partners Healthcare. A. Hemmerich: Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc. D. Duncan: Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc. C. Edgerly: Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc. R. Huang: Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc.; Licensing/Royalties, IHC patent: Roche/Ventana. M. Hiemenz: Full/Part-time employment: Foundation Medicine Inc. P. Reddy: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc. K. McGregor: Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc. J. Venstrom: Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc.; Full/Part-time employment: Genentech. A.B. Schrock: Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc. J.S. Ross: Leadership role, Research grant/Funding (self), Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc.; Advisory/Consultancy: Celsius Therapeutics.

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Poster Display session

1807P - Real world data on 442 patients (p) with small cell lung cancer (SCLC) treated in the last ten years at Vall d’Hebron Hospital

Presentation Number
1807P
Speakers
  • Nadia Saoudi Gonzalez (Barcelona, Spain)
Date
17.09.2020

Abstract

Background

SCLC is a highly aggressive tumour, with diverse treatment (ttm) options and heterogeneous outcomes. Real world data on prognostic markers are scarce in the literature.

Methods

We performed a comprehensive analysis of clinical data of all SCLC p who received ttm in our centre from May 2009 to November 2019. We estimated overall survival (OS) from date of diagnosis with the Kaplan-Meier method. Cox models were used to estimate hazard ratios (HR) and to assess OS prognostic factors.

Results

442p were included, 76% were male, median age was 65 years (y) and 8p (2%) were non-smokers. ECOG was 1 in most cases (57%) 317p (72%) were metastatic (met) at diagnosis, 17p (4%) had surgical ttm. Overall median OS (mOS) was 11.6m (CI95% 10-12.7). A total of 159p (36%) participated in clinical trials (CT), most of them (60%) in 2nd line (2L). 316p received 1st L based on platinum in met setting: 247 (78%) with carboplatin (CB) + etoposide (ET) and 69p (21%) with cisplatin (CD) + ET. 2nd L was offered to 162p (51%), mostly CT in 74p (46%), topotecan (TP) in 29%, CB + paclitaxel (TAX) in 14%, CB + ET in 11%. 3rd L was offered to 63p (20%), 30% were treated with CB + TAX, 28% participated in CT, 21% were treated with TP and 21% with other regimens. Furthermore, 39p (12%) received 4th or 5th L. From 108p (23%) that presented with initial locally-advanced disease and were treated with thoracic radiotherapy, ET + CB was offered to 62p (57%) or CD to 46p (43%). 66p (61%) achieved partial response. 68p (63%) were treated with prophylactic cranial irradiation (PCI). Elderly p were represented in our cohort: 147p (34%) were 70y or older; 73% (107p) had met at diagnosis. Inclusion ratio in CT was similar to general population (39p, 26%). 29p (20%) underwent PCI. In OS Cox model, respiratory failure (HR: 1.9, p=0.005), and met disease at diagnosis (HR 2.4 p<0.001) were associated with worse outcomes. p included in CT had longer median OS than those not eligible to CT (15.2m vs 8.4m HR 0.7 p=0.006).

Conclusions

This large cohort captures the scenario of daily management of SCLC p in the last 10 years and confirms his poor OS. This information is necessary to better understand the evolution of SCLC in clinical practice and as background for evaluation of new strategies to improve outcomes in this disease.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

A. Navarro: Advisory/Consultancy: Bristol-Myers Squibb Recipient; Advisory/Consultancy: F. Hoffmann La Roche AG; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Oryzon Genomics; Travel/Accommodation/Expenses: F. Hoffmann La Roche AG; Travel/Accommodation/Expenses: Bristol-Myers Squibb; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Merck Sharp & Dohme; Travel/Accommodation/Expenses: Boehringer Ingelheim. G. Villacampa Javierre: Speaker Bureau/Expert testimony: Merck; Advisory/Consultancy: AstraZeneca. P. Iranzo: Advisory/Consultancy: Bristol-Myers Squibb Recipient; Advisory/Consultancy: F. Hoffmann La Roche AG; Advisory/Consultancy: Merck Sharp & Dohme; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: MSD Oncology; Advisory/Consultancy: Rovi; Advisory/Consultancy: Kyowa Kirin; Advisory/Consultancy: Grunenthal Pharma S.A.; Travel/Accommodation/Expenses: F. Hoffmann La Roche AG; Travel/Accommodation/Expenses: Bristol-Myers Squibb; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Merck Sharp & Dohme; Travel/Accommodation/Expenses: Boehringer Ingelheim; Travel/Accommodation/Expenses: Grunenthal Pharma S.A. A. Callejo: Advisory/Consultancy: Bristol-Myers Squibb Recipient; Advisory/Consultancy: F. Hoffmann La Roche AG; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: MSD Oncology; Advisory/Consultancy: Kyowa Kirin; Travel/Accommodation/Expenses: F. Hoffmann La Roche AG; Travel/Accommodation/Expenses: F. Hoffmann La Roche AG; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Boehringer Ingelheim; Travel/Accommodation/Expenses: MSD Oncology; Travel/Accommodation/Expenses: Celgene. N. Pardo: Advisory/Consultancy: Bristol-Myers Squibb Recipient; Advisory/Consultancy: F. Hoffmann La Roche AG; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Boehringer Ingelheim; Travel/Accommodation/Expenses: F. Hoffmann La Roche AG; Travel/Accommodation/Expenses: Pfizer. S. Cedres: Advisory/Consultancy: Bristol-Myers Squibb Recipient; Advisory/Consultancy: F. Hoffmann La Roche AG; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: MSD Oncology; Advisory/Consultancy: Amphera; Travel/Accommodation/Expenses: F. Hoffmann La Roche AG; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Boehringer Ingelheim. A. Martinez-Marti: Advisory/Consultancy: Bristol-Myers Squibb Recipient; Advisory/Consultancy: F. Hoffmann La Roche AG; Advisory/Consultancy: Merck Sharp & Dohme; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: MSD Oncology; Speaker Bureau/Expert testimony: F. Hoffmann La Roche AG; Speaker Bureau/Expert testimony: Bristol-Myers Squibb Recipient; Speaker Bureau/Expert testimony: Merck Sharp & Dohme; Speaker Bureau/Expert testimony: Pfizer Recipient; Speaker Bureau/Expert testimony: Boehringer Ingelheim; Travel/Accommodation/Expenses: F. Hoffmann La Roche AG; Travel/Accommodation/Expenses: Bristol-Myers Squibb; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Merck Sharp & Dohme; Travel/Accommodation/Expenses: Boehringer Ingelheim. R. Dienstmann: Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy: Boehringer Ingelheim; Speaker Bureau/Expert testimony: Ipsen; Speaker Bureau/Expert testimony: Amgen; Speaker Bureau/Expert testimony: Servier; Speaker Bureau/Expert testimony: Sanofi; Speaker Bureau/Expert testimony: Merck Sharp & Dohme; Research grant/Funding (self): Merck; Research grant/Funding (self): Pierre Fabre. E. Felip: Advisory/Consultancy: AbbVie; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Blueprint medicines; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Celgene; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Guardant Health; Advisory/Consultancy: Janssen; Advisory/Consultancy: Medscape; Advisory/Consultancy: Merck KGaA; Advisory/Consultancy: Merck Sharp & Dohme; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Roche; Advisory/Consultancy: Takeda; Advisory/Consultancy: Touchtime; Research grant/Funding (institution): Fundación Merck Salud; Research grant/Funding (institution): Grant for Oncology Innovation EMD Serono. All other authors have declared no conflicts of interest.

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