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Massimo Di Maio
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MA26 - New Therapies and Emerging Data in ALK, EGFR and ROS1 (ID 930)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 13:30 - 15:00, Room 201 BD
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MA26.02 - Upfront or Sequential Strategy for New Generation Anaplastic Lymphoma Kinase (ALK) Inhibitors: An Italian Retrospective Study. (ID 12790)
13:35 - 13:40 | Author(s): Massimo Di Maio
- Abstract
- Presentation
Background
Anaplastic lymphoma kinase (ALK) rearrangement confers sensitivity to ALK inhibitors (ALKis) in non-small-cell lung cancer (NSCLC). Although several drugs provided an impressive outcome benefit, the most effective sequential strategy is still unknown.
a9ded1e5ce5d75814730bb4caaf49419 Method
We retrospectively collected 242 ALK-positive advanced NSCLC diagnosed between 2010 and 2018 in 23 Italian institutions (expanded data collection from Gobbini et al. Lung Cancer 2017). 138 patients received exclusively crizotinib as ALKi (not considered for this analysis). 78 patients received crizotinib and a new (second or third) generation ALKis as further treatments (group A). 26 patients performed a new generation ALKi as upfront agent (group B). These groups are larger than those considered in a previous analysis (15 and 8 patients, respectively).
4c3880bb027f159e801041b1021e88e8 Result
Study population clinical features and treatments received are summarized in Table 1.
Group A
Crizotinib followed by new generation ALKis
N= 78
Group B
Upfront new generation ALKis
N=26
Treatments per line n(%)
1°
2°
3°
4°
1°
2°
3°
4°
Crizotinib
28(36)
50(64)
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-
-
-
2(8)
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Alectinib
-
11(14)
18(23)
5(17)
7(27)
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Ceritinib
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9(12)
23(30)
3(4)
8(31)
8(31)
1(4)
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Brigatinib
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6(8)
6(8)
2(3)
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2(8)
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2(8)
Lorlatinib
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4(5)
5(6)
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1(4)
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Chemotherapy
50(64)
2(3)
10(13)
na
11(42)
6(23)
1(4)
Na
Clinical features n(%)
Age (range)
58 (27-83)
55 (24-82)
Male
37(47)
10(38)
p= 0.42
Female
41(53)
16(62)
Current smoker
8(10)
5(19)
p= 0.23
Never/former smoker
70(90)
21(81)
ALKi beyond PD
27(34)
4(15)
p= 0.06
With a median follow-up of 22.6 months (CI 95% 20.09-25.10), 33 patients had died (32%). In group B, the median progression free survival (PFS) for new generation ALKis administered as first (14.0 months, CI 95% 9.52-18.471), second (12.7 months, CI95% 7.22-18.17) or third-line (12.8 months, CI95% 6.24-19.35) was not statistically different (p= 0.522). The median time from the start of crizotinib to the disease progression after the new generation ALKi sequentially performed (group A) was longer than that one detected in group B for the upfront new generation ALKis (29 vs 14 months, HR 2.47 [CI95% 1.35-4.50], p=0.003). This result was confirmed even considering the time lost between the two treatments in group A. The median overall survival (OS) was not reached. The 12-months OS rate was 97% in group A and 84% in group B.
8eea62084ca7e541d918e823422bd82e Conclusion
New generation ALKis maintain their efficacy regardless of the treatment setting considered. The sequential strategy seems to provide a substantial benefit, but a longer follow-up and larger samples are needed to clarify the survival impact.
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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P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)
- 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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P1.13-16 - The Diagnostic Accuracy of Circulating Tumor DNA for the Detection of EGFR-T790M Mutation in NSCLC: A Systematic Review and Meta-Analysis (ID 14065)
16:45 - 18:00 | Author(s): Massimo Di Maio
- Abstract
Background
This meta-analysis aims at evaluating the diagnostic accuracy of circulating tumor (ct) DNA for the detection of epidermal growth factor receptor (EGFR)-T790M mutation in patients with EGFR-positive advanced non-small cell lung cancer (NSCLC) who progressed to prior EGFR-tyrosine kinase inhibitors (TKIs).
a9ded1e5ce5d75814730bb4caaf49419 Method
Data from published studies collecting matched blood and tumor tissue samples from patients with EGFR-positive advanced NSCLC who progressed to prior EGFR-TKI were collected by searching in PubMed, Cochrane Library, American Society of Clinical Oncology, European Society of Medical Oncology and World Conference of Lung Cancer meeting proceedings. Studies which evaluated both sensitivity and specificity of plasma-based EGFR-T790M mutation testing by ctDNA analysis were included and pooled sensitivity and specificity with 95% confidence intervals (95% CIs) were calculated.
4c3880bb027f159e801041b1021e88e8 Result
A total of twenty-one studies, with 1639 patients, were eligible. The pooled sensitivity of ctDNA analysis was 0.67 (95% CI: 0.64-0.70) and the pooled specificity was 0.80 (95% CI: 0.77-0.83). The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 2.67 (95% CI: 1.86-3.82) and 0.46 (95% CI: 0.38-0.54), respectively. The pooled diagnostic odds ratio (DOR) was 7.27 (4.39-12.05) and the AUC of the sROC curve was 0.77. Subgroup analysis by different detection platforms showed that sensitivity, specificity and AUC of ctDNA analysis by real-time (RT)-PCR were: 0.61 (95% CI: 0.57-0.65), 0.82 (95% CI: 0.77-0.87), and 0.70; sensitivity, specificity and AUC of ctDNA analysis by digital (d)PCR were: 0.72 (95% CI: 0.68-0.76), 0.73 (95% CI: 0.67-0.79), and 0.77; sensitivity, specificity and AUC of ctDNA analysis by by next-generation sequencing (NGS) were: 0.87 (95% CI: 0.76-0.95), 0.89 (95% CI: 0.82-0.94), and 0.88, respectively.
8eea62084ca7e541d918e823422bd82e Conclusion
The ctDNA analysis represents a promising, non-invasive approach to detect and monitor the T790M mutation status in patients with EGFR-positive advanced NSCLC, with NGS emerging as the most accurate detection platform. Development of standardized methodologies and clinical validation are recommended.
6f8b794f3246b0c1e1780bb4d4d5dc53
