Virtual Library
Start Your Search
Solange Peters
Author of
-
+
JCSE 01 - Joint IASLC/CSCO/CAALC Session: Immunotherapy for Management of Lung Cancer: Ongoing Research from East and West (ID 630)
- Event: WCLC 2017
- Type: Joint Session IASLC/CSCO/CAALC
- Track: Immunology and Immunotherapy
- Presentations: 2
- Moderators:C. Bai, Fred R. Hirsch, Tony SK Mok, Yi-Long Wu
- Coordinates: 10/15/2017, 07:30 - 11:30, F203 (Annex Hall)
-
+
JCSE 01.09 - Therapeutic Practices in Europe for Immunotherapy, including Biomarkers (ID 8228)
07:30 - 11:30 | Presenting Author(s): Solange Peters
- Abstract
- Presentation
Abstract not provided
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
JCSE 01.27 - Patients with ALK IHC-Positive/FISH-Negative NSCLC Benefit from ALK TKI Treatment: Response Data from the Global ALEX Trial (ID 10923)
07:30 - 11:30 | Author(s): Solange Peters
- Abstract
Background:
Patients with ALK-positive NSCLC have seen significant advances and increased options in ALK targeted therapies recently, and therefore rely on high quality, robust ALK status testing. Fluorescence in-situ hybridization (FISH) and immunohistochemistry (IHC) are the most common methods to determine ALK status for ALK tyrosine kinase inhibitor (TKI) treatment. However, availability of clinical outcome data from randomized trials linked directly to specific methods is limited. The ALEX trial (BO28984, NCT02075840) provides a unique dataset to assess ALK IHC- and FISH-based assays regarding clinical outcome for alectinib and crizotinib, particularly for the subset of patients with IHC-positive/FISH-negative NSCLC.
Method:
The VENTANA ALK (D5F3) CDx Assay (ALK IHC) performed in central laboratories was used as an enrollment assay for the selection of patients with ALK-positive NSCLC for inclusion in the ALEX trial. Additional samples from these patients were retrospectively tested in central laboratories with the Vysis ALK Break Apart FISH Probe Kit (ALK FISH).
Result:
Overall, 303 patients all with ALK IHC-positive NSCLC were randomized in the ALEX trial, of those 242 patients also had a valid ALK FISH result, with 203 patients having ALK FISH-positive disease and 39 patients having ALK FISH-negative disease (alectinib, n=21; crizotinib, n=18). For 61 of 303 (20.1%) patients with an ALK IHC-positive result, a valid ALK FISH result could not be obtained due to the test leading to an uninformative FISH result (10.9%), or not having adequate/no tissue available (9.2%). Ventana IHC staining success rates were higher than for Vysis FISH testing for the ALEX samples. Exploratory analysis of investigator-assessed progression-free survival (PFS) in patients with a FISH-positive result (HR 0.40, 95% CI 0.27–0.61; p<0.0001; median not reached [alectinib] versus 12.7 months [crizotinib]) was consistent with the primary endpoint analysis in the Ventana ALK IHC-positive population. Patient outcome data show that 28% of central ALK IHC-positive/ALK FISH-negative samples were from patients who responded to ALK TKI treatment (complete response or partial response) and 33% had stable disease according to investigator assessment.
Conclusion:
This analysis shows that ALK IHC is a robust testing approach, which may identify more patients with a valid ALK testing result who benefit from ALK TKI treatment than ALK FISH testing. While PFS of patients with ALK FISH-positive NSCLC was similar to that of patients with ALK IHC-positive NSCLC, the analysis also revealed that the majority of patients with ALK IHC-positive/ALK FISH-negative NSCLC may derive clinical benefit from ALK TKI treatment.
-
+
MA 06 - Lung Cancer Biology I (ID 660)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Biology/Pathology
- Presentations: 1
- Moderators:N. Motoi, Keith M Kerr
- Coordinates: 10/16/2017, 15:45 - 17:30, Room 501
-
+
MA 06.06 - Assessment of RANK Prevalence and Clinical Significance in the NSCLC European Thoracic Oncology Platform Lungscape Cohort (ID 10006)
15:45 - 17:30 | Author(s): Solange Peters
- Abstract
- Presentation
Background:
Receptor Activator of Nuclear Factor κappa-B (RANK) is a pathway involved in bone homeostasis. Recent evidence suggests that RANK signalling may also play a role in bone metastasis, and primary breast and lung cancers. The European Thoracic Oncology Platform (ETOP) Lungscape project allows evaluation of the prevalence of RANK expression and its clinical significance in a cohort of surgically-resected NSCLCs.
Method:
RANK expression was assessed on tissue microarrays (TMAs) using immunohistochemistry. Up to 4 cores per patient were analysed based on sample acceptance criteria. An H-Score (staining intensity + % cells stained) was used to assess RANK expression (positivity), as defined by at least 1 core with any degree of positive staining. Prevalence of RANK positivity and its association with clinicopathological characteristics, other cancer-related biomarkers (IHC ALK/MET/PTEN/PD-L1 expression and EGFR/KRAS/PIK3CA mutations) and patient outcome [Relapse-free Survival (RFS), Time-to-Relapse (TTR), Overall Survival (OS)] was explored in a subset of the ETOP Lungscape cohort. The prevalence of RANK overexpression (proportion of positive cancer cells ≥50%) was also investigated.
Result:
RANK expression was assessed in patients from 3 centers, a total of 402 from the 2709 patients of the Lungscape cohort, with median follow-up 44 months; 32.6% female, 40.8/54.2/5.0% adenocarcinomas (AC)/squamous cell carcinomas (SCC)/other, 44.8/28.4/26.9% with stage I/II/III, 20.6/57.7/18.9% current/former/never smokers (and 2.7% with unknown smoking status). Median was 74 months for both RFS and OS, while median TTR was not reached. Prevalence of RANK positivity was 26.6% (107 of the 402 cases), with 95% confidence interval (95%CI):22.4%-31.2%; significantly higher in AC: 48.2% (79 of 164 cases), 95%CI:40.3%-56.1%; vs SCC: 9.2% (20 of 218 cases), 95%CI:5.7%-13.8%; (p<0.001). RANK positivity was more frequent in females (38.9% vs 20.7% in males, p<0.001) and tumors≤4cm (30.7% vs 21.1% in tumors>4cm, p=0.031). Significant associations were also detected between RANK and PTEN expression in AC (RANK positivity 57.4% in PTEN expression vs 30.5% in PTEN loss; p=0.0011) and with MET status in SCC (RANK positivity 27.8% in MET+ vs 7.6% in MET-; p=0.016). No association with outcome was found. RANK overexpression was identified in 43 (10.7%; 95%CI: 7.9%-14.1%) cases.
Conclusion:
In this early-stage NSCLC cohort, RANK positivity (26.6% overall) is found to be significantly more common in adenocarcinomas (48.2%), females, patients with tumors of smaller size, with PTEN expression (in SCC) and MET positivity (in AC). No prognostic significance of RANK expression was found. Analysis of additional cases is ongoing and results will be presented.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
MA 07 - ALK, ROS and HER2 (ID 673)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:Robert C. Doebele, J.C. Ho
- Coordinates: 10/17/2017, 15:45 - 17:30, Room 316
-
+
MA 07.01 - Patients with ALK IHC-Positive/FISH-Negative NSCLC Benefit from ALK TKI Treatment: Response Data from the Global ALEX Trial (ID 9008)
15:45 - 17:30 | Author(s): Solange Peters
- Abstract
- Presentation
Background:
Patients with ALK-positive NSCLC have seen significant advances and increased options in ALK targeted therapies recently, and therefore rely on high quality, robust ALK status testing. Fluorescence in-situ hybridization (FISH) and immunohistochemistry (IHC) are the most common methods to determine ALK status for ALK tyrosine kinase inhibitor (TKI) treatment. However, availability of clinical outcome data from randomized trials linked directly to specific methods is limited. The ALEX trial (BO28984, NCT02075840) provides a unique dataset to assess ALK IHC- and FISH-based assays regarding clinical outcome for alectinib and crizotinib, particularly for the subset of patients with IHC-positive/FISH-negative NSCLC.
Method:
The VENTANA ALK (D5F3) CDx Assay (ALK IHC) performed in central laboratories was used as an enrollment assay for the selection of patients with ALK-positive NSCLC for inclusion in the ALEX trial. Additional samples from these patients were retrospectively tested in central laboratories with the Vysis ALK Break Apart FISH Probe Kit (ALK FISH).
Result:
Overall, 303 patients all with ALK IHC-positive NSCLC were randomized in the ALEX trial, of those 242 patients also had a valid ALK FISH result, with 203 patients having ALK FISH-positive disease and 39 patients having ALK FISH-negative disease (alectinib, n=21; crizotinib, n=18). For 61 of 303 (20.1%) patients with an ALK IHC-positive result, a valid ALK FISH result could not be obtained due to the test leading to an uninformative FISH result (10.9%), or not having adequate/no tissue available (9.2%). Ventana IHC staining success rates were higher than for Vysis FISH testing for the ALEX samples. Exploratory analysis of investigator-assessed progression-free survival (PFS) in patients with a FISH-positive result (HR 0.40, 95% CI 0.27–0.61; p<0.0001; median not reached [alectinib] versus 12.7 months [crizotinib]) was consistent with the primary endpoint analysis in the Ventana ALK IHC-positive population. Patient outcome data show that 28% of central ALK IHC-positive/ALK FISH-negative samples were from patients who responded to ALK TKI treatment (complete response or partial response) and 33% had stable disease according to investigator assessment.
Conclusion:
This analysis shows that ALK IHC is a robust testing approach, which may identify more patients with a valid ALK testing result who benefit from ALK TKI treatment than ALK FISH testing. While PFS of patients with ALK FISH-positive NSCLC was similar to that of patients with ALK IHC-positive NSCLC, the analysis also revealed that the majority of patients with ALK IHC-positive/ALK FISH-negative NSCLC may derive clinical benefit from ALK TKI treatment.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
MS 12 - Sustainable Care System in Each Region (ID 534)
- Event: WCLC 2017
- Type: Mini Symposium
- Track: Regional Aspects/Health Policy/Public Health
- Presentations: 1
- Moderators:Yasushi Goto, M.E. Hand
- Coordinates: 10/17/2017, 11:00 - 12:30, Room 501
-
+
MS 12.02 - Sustainable Care System in Europe (ID 8122)
11:00 - 12:30 | Presenting Author(s): Solange Peters
- Abstract
Abstract not provided
Information from this presentation has been removed upon request of the author.
-
+
P1.04 - Clinical Design, Statistics and Clinical Trials (ID 690)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Clinical Design, Statistics and Clinical Trials
- Presentations: 2
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
-
+
P1.04-008 - POSEIDON: A Phase 3 Study of First-Line Durvalumab ± Tremelimumab + Chemotherapy vs Chemotherapy Alone in Metastatic NSCLC (ID 8666)
09:30 - 16:00 | Author(s): Solange Peters
- Abstract
Background:
Immunotherapy is an important new treatment modality for NSCLC. Dual blockade of the non-redundant PD-1/PD-L1 and CTLA-4 pathways may provide additive or synergistic effects. Durvalumab is a selective, high-affinity, engineered human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80. Tremelimumab is a selective human IgG2 mAb against CTLA-4. A combination regimen of immunotherapy with chemotherapy may further enhance clinical benefit. In a Phase 1b study (NCT02537418), durvalumab ± tremelimumab combined with chemotherapy demonstrated manageable tolerability and preliminary signs of clinical activity in patients with solid tumors, including NSCLC.
Method:
POSEIDON (NCT03164616) is a Phase 3, randomized, multicenter, open-label, global study to investigate durvalumab ± tremelimumab + platinum-based chemotherapy vs platinum-based chemotherapy alone as first-line treatment in metastatic NSCLC. Patients must be immunotherapy- and chemotherapy-naïve with EGFR/ALK wild-type metastatic NSCLC, and have confirmed tumor PD-L1 expression status, and a WHO/ECOG performance status of 0/1. Approximately 801 patients will be randomized 1:1:1 to receive durvalumab + tremelimumab + chemotherapy (Arm 1); durvalumab + chemotherapy (Arm 2); or chemotherapy alone (Arm 3). After induction, patients in the immunotherapy arms will receive durvalumab monotherapy, and non-squamous patients who initially received pemetrexed during induction will receive it as maintenance therapy if eligible. Treatment will continue until disease progression or another discontinuation criterion has been met. The primary endpoint is PFS according to blinded independent central review (RECIST v1.1). Secondary endpoints include OS; ORR; duration of response; best overall response; proportion of patients alive and progression-free at 12 months; disease-related symptoms and HRQoL; and safety and tolerability. Recruitment is ongoing.Figure 1
Result:
Section not applicable
Conclusion:
Section not applicable
-
+
P1.04-011 - Development of Novel Blood-Based Biomarker Assays in 1L Advanced/ Metastatic NSCLC: Blood First Assay Screening Trial (BFAST) (ID 8398)
09:30 - 16:00 | Author(s): Solange Peters
- Abstract
Background:
Worldwide it is estimated that 20%-30% of advanced NSCLC patients do not receive a complete molecular diagnosis at baseline and are ineligible for targeted therapies due to tissue biopsy limitations. Blood-based, multiplex testing that analyzes circulating tumor DNA (ctDNA) by targeted next-generation sequencing offers a minimally invasive testing method, but clinical utility has yet to be established. High tumor mutational burden (TMB) measured in tissue is associated with atezolizumab (anti–PD-L1) clinical activity in several tumor types, including NSCLC. Alectinib, a potent, selective ALK/RET kinase inhibitor, has shown activity in 1L and is approved as 2L therapy in patients with ALK- or RET-positive advanced NSCLC but requires tissue for analysis. Here we present an umbrella trial that aims to clinically validate novel blood-based diagnostic assays that measure TMB in the blood (bTMB) and somatic mutations (e.g., ALK/RET), and to determine the efficacy and safety of 1L atezolizumab or alectinib in biomarker-selected NSCLC patients.
Method:
BFAST is a Phase II/III global, multicenter, open-label, multi-cohort screening and interventional umbrella trial designed to evaluate the safety and efficacy of targeted therapies in patients with unresectable, advanced or metastatic NSCLC selected based on the presence of oncogenic somatic mutations or a positive bTMB score. Key eligibility criteria include previously untreated, stage IIIB-IVB NSCLC of any histology and measurable disease per RECIST v1.1. Pre-enrollment blood-based screening will identify patients whose tumors harbor oncogenic somatic mutations (ALK/RET) or a positive bTMB score (above a pre-specified cutoff); patients will be assigned to the appropriate cohort based on the screening results. Study treatment will continue until disease progression (all cohorts) or loss of clinical benefit (atezolizumab only) (Table). The modular trial design allows for additional biomarker-driven BFAST cohorts with distinct screening and treatment requirements, and endpoints such as ORR with highly active drugs.Table. BFAST Study Details Cohort Treatment Planned Enrollment, n Primary Endpoints Key Secondary Endpoints Cohort AALK+ Alectinib 600 mg PO bid 78 ORR per RECIST v1.1 (INV-assessed) DOR, CBR[c] and PFS per RECIST v1.1 (INV-assessed) ORR, DOR, CBR and PFS per RECIST v1.1 (IRF-assessed) OS Cohort B RET+ Alectinib 900 and 1200 mg dose escalation 52-62 ORR per RECIST v1.1 (INV-assessed) DOR, CBR and PFS per RECIST v1.1 (INV-assessed) ORR, DOR, CBR and PFS per RECIST v1.1 (IRF-assessed) OS Cohort C bTMB+ Atezolizumab 1200 mg IV q3w or platinum-based chemotherapy[a] ≈440 (R, 1:1)[b] PFS per RECIST v1.1 (INV-assessed) OS PFS, ORR and DOR per RECIST v1.1 (IRF-assessed) ORR and DOR per RECIST v1.1 (INV-assessed) 6- and 12-month PFS rates [a ]Cisplatin or carboplatin + pemetrexed for non-squamous histology, and cisplatin or carboplatin + gemcitabine for squamous histology. Administered per standard of care. [b ]Stratification factors include tissue availability, ECOG performance status, bTMB level and tumor histology. [c ]CBR is defined as the rate of patients with confirmed CR or PR or stable disease that has been maintained for ≥ 24 weeks. bid, twice a day; bTMB, blood tumor mutational burden; CBR, clinical benefit rate; INV, investigator; IRF, independent review facility; IV, intravenously; PO, orally; q3w, every 3 weeks; R, randomized.
Result:
Section not applicable
Conclusion:
Section not applicable
