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Céline Mascaux
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MA04 - Novel Approaches with IO (ID 900)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Immunooncology
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 13:30 - 15:00, Room 107
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MA04.03 - Immunotherapy for Non-Small Cell Lung Cancers (NSCLC) with Oncogenic Driver Mutations: New Results from the Global IMMUNOTARGET Registry (ID 13187)
13:40 - 13:45 | Author(s): Céline Mascaux
- Abstract
- Presentation
Background
Prospective data on immunotherapy for NSCLC with oncogenic driver mutations are limited. We recently reported first results from the global IMMUNOTARGET registry (Mazières, ASCO 2018). Here, we present new data for PD-L1 and mutation subgroups.
a9ded1e5ce5d75814730bb4caaf49419 Method
In 2017, we started an international retrospective registry study ("IMMUNOTARGET") for patients with advanced NSCLC, known driver mutations (KRAS, EGFR, ALK, ROS1, BRAF, HER2, MET and RET) and PD-L1 immune checkpoint inhibitor therapy. The registry is approved by University of Toulouse and Swissethics, and funded by University of Toulouse and Cantonal Hospital of Lucerne. Anonymized real-world data submitted to the coordinating center include: patient and tumor characteristics, mutation test methods and results, systemic therapy lines, immune related adverse events, best response by RECIST, survival, and tumor PD-L1 expression (optional). Statistical calculations including best response, median PFS and OS are done at University of Toulouse.
4c3880bb027f159e801041b1021e88e8 Result
In April 2018, the registry included 551 pts from Europe, USA, Israel and Australia. Patients were 50% male/female, 28% current smokers, median age 60 years (range 28-83), 85% had PS0/1. Most (73%) tumors were stage IV at diagnosis, almost all (96%) were adenocarcinomas. Molecular classification by dominant driver mutation: KRAS=271 (49%), EGFR=125 (23%), BRAF=43 (8%), MET=36 (7%), HER2=29 (5%), ALK=23 (4%), RET=16 (3%), ROS1=7 (1%), 1 (0.2%) not classified (ALK+RET+MET). Most pts received nivolumab (466) or pembrolizumab (48) and were treated with immunotherapy in second or third line (67%). The median number of cycles was 5 (range 1-68). Fifty (11%) pts had grade 3-5 toxicity. Median OS from start of immunotherapy was 13.3 months, median PFS was 2.8 months. Best response was PR/CR in: KRAS=26%, BRAF=24%, ROS1=17%, MET=16%, EGFR=12%, HER2=7%, RET=6%, ALK=0%. Percentage of PD-L1 positive cells was available for 177 pts: 0%=71 (40%), 1-49%=46 (26%), 50-100%=60 (34%). Median % of positive cells was highest for ROS1 (90%), BRAF (50%), MET (30%) and RET (26%) mutant tumors. PD-L1 positivity was predictive for improved PFS in KRAS and EGFR mutant tumors. PD-L1 status was known in 18 tumors with ALK, ROS1 or RET rearrangements: 5 had 0%, 4 had 1-49% and 9 had 50%-100%. No tumor remissions were observed in this subgroup. The registry remains open, updated results will be presented at the conference.
8eea62084ca7e541d918e823422bd82e Conclusion
Although response rates were lower than in KRAS mutant NSCLC, individual tumors with other driver mutations responded to immunotherapy. PD-L1 expression may not accurately predict clinical benefit from immunotherapy in some molecular subgroups, better markers are needed.
6f8b794f3246b0c1e1780bb4d4d5dc53Only 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.
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MA22 - New Therapeutics, Pathology, and Brain Metastases for Small Cell and Neuroendocrine Tumour (ID 925)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 15:15 - 16:45, Room 206 BD
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MA22.04 - Discussant - MA 22.01, MA 22.02, MA 22.03 (ID 14617)
15:30 - 15:45 | Presenting Author(s): Céline Mascaux
- 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.
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P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- 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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P1.01-04 - Treatment Patterns and Overall Survival Following Biomarker Testing in Real-World Advanced NSCLC Patients (ID 12743)
16:45 - 18:00 | Author(s): Céline Mascaux
- Abstract
Background
Foundation Medicine (FMI) comprehensive genomic profiling and other next-generation sequencing (NGS) tests are gaining importance in routine clinical management of non-small cell lung cancer (NSCLC). They assess multiple genetic alterations that drive sensitivity or resistance to treatment, enabling optimal therapeutic decisions. We evaluated the effect of biomarker testing on treatment patterns and overall survival (OS) in real-world advanced NSCLC (aNSCLC) patients receiving different test types, and in non-tested patients.
a9ded1e5ce5d75814730bb4caaf49419 Method
The Flatiron Health (FH) Database comprises patient-level electronic health records from a large network of US cancer clinics. Patients had aNSCLC diagnoses between 01/2013 and 05/2017, ≥2 clinic visits in the FH network, first treatment starting ≤90 days after aNSCLC diagnosis, and biomarker tests before first treatment. Testing data were abstracted for five biomarkers (EGFR, ALK, KRAS, ROS1, and PD-L1). Patients were hierarchically categorized into three testing groups: FMI, other NGS, and single-biomarker non-NGS. Biomarker status and patterns in first treatment were described. Cox proportional hazards models were used to compare OS among testing groups and non-tested patients.
4c3880bb027f159e801041b1021e88e8 Result
As of 11/30/2017, 355 patients had ≥1 FMI test, 780 had ≥1 other NGS test, and 6,363 had ≥1 non-NGS test prior to first treatment; 5,148 patients were never tested. Table 1 summarizes biomarker status, treatment patterns, and results of multivariate survival models adjusted for baseline demographic and clinical differences among testing groups. Patients with FMI tests were more likely to receive NCCN-recommended targeted treatments. Better OS was observed for FMI, other NGS, and non-NGS compared with non-tested patients.
FMI
Other NGS
Non-NGS
Non-tested
(n = 355)
(n = 780)
(n = 6,363)
(n = 5,148)
n
%
n
%
n
%
n
%
Biomarker status1
EGFR mutation
51
14.4
121
15.5
853
13.4
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ALK rearrangement
8
2.3
23
2.9
187
2.9
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ROS1 rearrangement
0
0
3
0.4
33
0.5
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KRAS mutation
94
26.5
189
24.2
415
6.5
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PD-L1-positive
21
5.9
112
14.4
234
3.7
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Patterns in first treatment
NCCN-recommended
targeted therapy2,377
21.7
129
16.5
1,037
16.3
112
2.2
Non NCCN-recommended targeted therapy2,4
2
0.6
3
0.4
11
0.2
40
0.8
NCCN-recommended ICI2,5
36
10.1
102
13.1
381
6.0
229
4.4
Non NCCN-recommended ICI2,6
2
0.6
0
0
8
0.1
3
0.1
Multivariate Cox proportional hazards model to compare OS, hazard ratio (95% CI)
All aNSCLC7
0.72*
(0.61, 0.85)
0.74*
(0.66, 0.83)
0.78*
(0.74, 0.83)
1.00
(ref)
aNSCLC, non-squamous
cell histology80.69*
(0.61, 0.79)
0.76*
(0.70, 0.80)
0.69*
(0.57, 0.83)
1.00
(ref)
All aNSCLC9
0.93
(0.77, 1.13)
1.05
(0.92, 1.21)
1.00
(ref)
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aNSCLC, non-squamous
cell histology100.91
(0.74, 1.13)
1.01
(0.87, 1.17)
1.00
(ref)
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aNSCLC, non-EGFR-mutated, non-ALK-rearranged, non-squamous cell histology11
0.9
(0.74, 1.10)
0.94
(0.82, 1.08)
1.00
(ref)
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ECOG, Eastern Cooperative Oncology Group; ICI, immune checkpoint inhibitor; NCCN, National Comprehensive Cancer Network.1 Denotes biomarker status overall prior to starting first treatment and represents overall status from all test-types. In case of multiple tests, the following hierarchy is used: positive>negative>pending/unsuccessful/indeterminate/unknown.
2 Based on the NSCLC NCCN Guidelines, Version 3. 2018; 02/21/2018.
3 NCCN-recommended targeted therapy implies treatment regimens containing at least one of the following: erlotinib, afatinib, gefitinib, osimertinib, crizotinib, ceritinib, alectinib, brigatinib, dabrafenib+trametinib, cabozantinib, vandetanib, ado-trastuzumab emtansine.
4 Non NCCN-recommended targeted therapy implies treatment regimens containing at least one of the following: necitumumab, cetuximab, panitumumab, vemurafenib, dabrafenib, trametinib, trastuzumab, pertuzumab+trastuzumab, venetoclax.
5 NCCN-recommended ICI implies treatment regimens containing at least one of the following: pembrolizumab, nivolumab, atezolizumab.
6 Non NCCN-recommended ICI implies treatment regimens containing at least one of the following: ipilimumab, avelumab.
7 Adjusted for age, sex, race, clinic type, payer type, smoking history, stage at initial diagnosis, ECOG performance status, histology, and year of advanced diagnosis.
8 Adjusted for age, sex, race, clinic type, payer type, smoking history, stage at initial diagnosis, ECOG performance status, and year of advanced diagnosis.
9 Adjusted for age, sex, race, clinic type, payer type, smoking history, stage at initial diagnosis, ECOG performance status, histology, year of advanced diagnosis, sample type used for the test, and biomarker status.10 Adjusted for age, sex, race, clinic type, payer type, smoking history, stage at initial diagnosis, ECOG performance status, year of advanced diagnosis, sample type used for test, and biomarker status.
11 Adjusted for age, sex, race, clinic type, smoking history, stage at initial diagnosis, ECOG performance status, and year of advanced diagnosis.
* Indicates a statistically significant estimate (p<0.05).
8eea62084ca7e541d918e823422bd82e Conclusion
Complexity of real-world aNSCLC biomarker testing and associated treatments creates challenges when comparing OS among testing groups. In the future, as more treatments targeting a wider array of genomic alterations become available and accessible, the utility of NGS-based assays to guide NCCN-recommended treatments with actionable targets and differences in OS may become more apparent.
6f8b794f3246b0c1e1780bb4d4d5dc53
