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Anne-Marie Dingemans
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FP12 - Tumor Biology and Systems Biology - Basic and Translational Science (ID 188)
- Event: WCLC 2020
- Type: Posters (Featured)
- Track: Tumor Biology and Systems Biology - Basic and Translational Science
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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FP12.06 - GRIm-Score Variations Predict Outcome in Metastatic NSCLC Patients Treated with First-Line Pembrolizumab (ID 3363)
00:00 - 00:00 | Author(s): Anne-Marie Dingemans
- Abstract
Introduction
Prompt identification of metastatic non-small cell lung cancer patients (NSCLC) who benefit from first-line pembrolizumab is crucial in clinical practice. The Gustave Roussy Immune Score (GRIm-score) takes into account neutrophil-to-lymphocyte ratio (NLR), serum albumin concentration and lactate dehydrogenase (LDH) and its prognostic score has been investigated in patients treated with immune check-point inhibitors (ICIs). To further assess the predictive value of baseline GRIm-score (GRImT0), we separately investigated two cohorts of metastatic NSCLC patients treated with first-line pembrolizumab immunotherapy or chemotherapy (CHT). We also investigated whether GRIm-score at 45 days since treatment initiation (GRImT1) and GRIm-score deterioration between the two time points may better predict clinical outcomes.
Methods
We retrospectively evaluated 222 metastatic NSCLC patients: 135 treated with pembrolizumab and 87 treated with chemotherapy. NLR, serum albumin and LDH concentrations were assessed at T0 and at T1. According to the GRIm-score, patients were assigned 1 point if they had NLR > 6, LDH > upper limit normal or albumin < 3.5 g/dl, for a total of 3 points. Patients with a GRIm-score <2 were considered as having a low Score. Chi-squared test was used to evaluate the association between variables. Median overall survival (OS) and progression free survival (PFS) were estimated by Kaplan-Meier method and log-rank test was used to assess differences by subgroups. The independent prognostic and predictive role of the scores was further analysed by multivariate logistic regression and Cox proportional hazard analyses.
Results
Median follow up of the whole population was 24.0 months, median OS and PFS were 12.0 months and 6.5 months, respectively. In both cohorts, no difference in terms of OS between patients with low and high GRImT0 was found. Otherwise, median OS and PFS of the low GRImT1 group were significantly longer than those of the high GRImT1 group in pembrolizumab-treated patients, but not in the CHT cohort (pembrolizumab cohort: low vs. high; median OS not reached vs. 9.2 months, p = 0.004 and median PFS 10.8 vs. 2.3 months, p = 0.002). The outcome of patients receiving pembrolizumab with no GRIm deterioration was better compared to patients with GRIm deterioration in terms of OS (median OS not reached vs. 12.0 months, p < 0.001), PFS (median PFS 20.6 vs. 2.6 months, p < 0.001) and objective response rate (58.2% vs 7.6%, p = 0.003). The prognostic and predictive role of GRImT1 and of GRIm deterioration in the pembrolizumab-cohort was also confirmed at multivariate analyses, after adjusting for performance status (PS), smoking and disease burden (high GRImT1 HR for death: 2.63, 95% CI 1.18-5.86, p = 0.01, GRIm deterioration HR for death: 3.28, 95% CI 1.39-7.74, p = 0.006).
Conclusion
Our data shown that GRImT1 and GRIm deterioration are more reliable predictors of outcome compared to GRImT0 in NSCLC patients treated with pembrolizumab. Their prognostic and predictive value was independent of PS, smoking and disease burden. Both GRImT1 and GRIm deterioration represent useful and easy-to-access early indicators of treatment response in metastatic NSCLC patients treated with first-line pembrolizumab and might help guiding clinicians’ choices in this setting.
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MA12 - Controversies Old and New (ID 230)
- Event: WCLC 2020
- Type: Mini Oral
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Moderators:
- Coordinates: 1/31/2021, 16:45 - 17:45, Scientific Program Auditorium
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MA12.12 - Discussant (ID 4207)
16:45 - 17:45 | Presenting Author(s): Anne-Marie Dingemans
- Abstract
Abstract not provided
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P09 - Health Services Research/Health Economics - Real World Outcomes (ID 121)
- Event: WCLC 2020
- Type: Posters
- Track: Health Services Research/Health Economics
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P09.18 - COVID-19 Outcomes in Patients With Thoracic Malignancies According to Gender and Ethnicity (TERAVOLT) (ID 3702)
00:00 - 00:00 | Author(s): Anne-Marie Dingemans
- Abstract
Introduction
Previously reported data on patients with thoracic malignancies who develop COVID-19 have suggested a higher mortality rate compared to the general population and to other cancer types, particularly in patients over 65 years of age or suffering from active or progressive disease. Preliminary data from other studies have suggested that gender and ethnicity may also impact patient outcomes.
Methods
TERAVOLT is a multi-center, international observational study composed of a cross-sectional component and a longitudinal cohort component. Eligibility criteria include the presence of any thoracic cancer and a COVID-19 diagnosis confirmed in the laboratory with RT-PCR/serology, highly suspicious radiological and clinical findings, or suspected with symptoms and known contact with a positive person. The overarching goals of this consortium are to provide data for guidance to oncology professionals on managing patients with thoracic malignancies while understanding the risk factors for morbidity and mortality from this novel virus. Clinical outcomes including hospitalization, ICU admission, oxygen requirement and mortality were collected. The association between demographic/clinical characteristics and outcomes were measured with odds ratio with 95% confidence intervals using a logistic regression model.
Results
As of August 20, 2020, a total of 1,053 patients with COVID-19 and thoracic cancers from 19 countries and 130 centers have been identified, including 42% females and 84% White, 9.3% African American, 25% Hispanic. The median age of male patients was 69 compared to 66 years of age for females. While ECOG PS was similar between treatment groups, 77% of males were admitted to hospital with a mortality rate of 37% compared to 66% of females with a mortality rate of 28%. The median age of African American patients was 66 years of age compared to 68 and 69 years of age for white and Hispanic patients, respectively; 26% of African American and 25% White patients had an ECOG PS ≥2 compared to 19% of Hispanics. A similar percentage of patients were admitted to the hospital and ICU, while the mortality rate for Hispanics was 36% compared to 34% for whites and 26% for African Americans.
Conclusion
Similar to the general population, the mortality rate of males with thoracic cancer is higher than females. Regarding ethnicity, there is a difference in the median age of African American patients compared to Whites and Hispanics. Although the severity of COVID-19 disease, as defined by hospital admission, is similar between ethnic groups, the mortality rate in Hispanics is higher. We will present a multivariate analysis of these data according to gender and ethnicity, including the impact of cancer stage, prior cancer therapy, and COVID-19 therapy on outcomes.
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P84 - Targeted Therapy - Clinically Focused - ALK (ID 261)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P84.01 - The ARIA Study: Activity of Next-Generation ALK TKIs Based on ALK Resistance Mutations Detected by Liquid Biopsy in ALK Positive NSCLC Patients. (ID 3092)
00:00 - 00:00 | Author(s): Anne-Marie Dingemans
- Abstract
Introduction
Detection of resistance mechanisms to tyrosine kinase inhibitors (TKI), in particular ALK mutations (ALKm), could help to select the subsequent treatment in ALK-positive NSCLC patients. Liquid biopsy can identify these ALKm from ctDNA in up to 29% of patients after 2nd-generation TKI-failure. We assessed the activity of next-gen TKIs based on the presence of ctDNA ALKm.
Methods
Patients with ALK-positive advanced NSCLC pretreated with 1st and/or 2nd-generation ALK-TKI were selected in 9 European centers. Liquid biopsy was collected immediately before starting brigatinib or lorlatinib. ALKm were defined by commercial or homemade next-generation sequencing run on ctDNA and covering ALK exon 22/23/25. We correlated the activity of brigatinib or lorlatinib based on three ctDNA molecular groups: presence ALKm (if one: single; if ≥2: complex); other mutations and no detectable mutations. We assessed progression-free survival (PFS), objective response rate (ORR), intracranial ORR according to the clinical routine of each center and overall survival (OS).
Results
62 patients were identified, 58 evaluable at cutoff data (Jul-20): 16 before brigatinib and 42 before lorlatinib. Median age was 53 [27-80], 64% were female, 67% nonsmoker; 97% with adenocarcinoma; 7% and 10% with isolated thoracic and brain disease, respectively. The median (m) number of TKIs was 3 [2-7]; 90% received 2nd-generation TKIs. The mFU since liquid biopsy was 24.8 months. ALKm were detected in 28% (3 brigatinib; 13 lorlatinib), 9 single and 7 complex; others were detected in 17% (n=10) and none in 55% (n=32). The most common mutation was G1202R (7 before lorlatinib), followed by G1269A and F1174L in 3 cases each, all pretreated with 2nd-generation TKIs. The TKI outcomes according to the ctDNA molecular groups is summarized in table 1. In the ALKm group, lorlatinib showed an ORR of 46% and 56% of intracranial ORR with mPFS of 6.5 months (7=single/6=complex) while no responses were observed in the 3 cases treated with brigatinib, with mPFS of 3.5 months (2=single/1=complex).Those 7 cases harboring the G1202Rmut (4=complex) had an ORR of only 14% but an intracranial ORR of 50%; mPFS was 3.6 mo. No differences were observed among ctDNA molecular groups.
ConclusionOverall
ALK mutations
Others
None
BRIGATINIB
N=16
n= 3
n=3
n= 10
PFS, median (95% CI)
5.6 months
(4.27-16.79)
3.5 months
(2.63-NR)
6.2 months
(4.27-NR)
8.1 months
(4.40-NR)
12 months-PFS rate
27.3 %
(11.9-62.6)
33.3%
(6.7-100)
0%
40%
(18.7-85.5)
ORR
27%
(4/15)
0%
(0/3)
67%
(2/3)
22%
(2/9)
ORR CNS
50%
(6/12)
0%
(0/2)
100%
(2/2)
50%
(4/8)OS*, median (95% CI)
62.6 months
(31.7-not reached)
38.4 months
(31.7-NR)
62.6 months
(21 .4-NR)
NR
(24.5-NR)
LORLATINIB
N= 42
n= 13
n= 7
n= 22
PFS, median (95% CI)
7.6 months
(5.26- 11.14)
6.5 months
(3.61-NR)
7.6 months
(5.22-NR)
7.3 months
(4.63-NR)
12 months-PFS rate
29.5%
(17.7-49.1)
30%
(12.0-74.7)
28.6%
(8.9-92.2)
30%
(14.6-61.6)
ORR
38%
(16/58)
46%
(6/13)
71%
(5/7)
23%
(5/22)
ORR CNS
62%
(18/29)
56%
(5/9)
60%
(3/5)
67%
(10/15)
OS*, median (95% CI)
55.5 months
(45.0-NR)
62.6 months
(54.8-NR)
45.0 months
(24.5-NR)
NR
(41.9-NR)
PFS: progression-free survival; ORR: objective response rate; CNS: central nervous system; OS: overall survival; *since systemic therapy start
In our study, lorlatinib showed activity in heavily-pretreated patients with ALK-positive NSCLC, regardless the ctDNA molecular groups. Poor outcomes were observed for brigatinib in 3 heavily-pretreated patients with ctDNA ALKm. The recent use of 2nd-gen TKI upfront calls for similar studies to confirm if ctDNA may be a biomarker for guiding the sequential therapy.
