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Giulio Rossi
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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: 2
- 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): Giulio Rossi
- 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.
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MA26.07 - ROS1 (SP384) Immunohistochemistry Inter-Reader Precision Between 12 Pathologists (ID 12387)
14:10 - 14:15 | Author(s): Giulio Rossi
- Abstract
- Presentation
Background
ROS1 positive non-small cell lung cancer (NSCLC) patients can be treated with specific tyrosine kinase inhibitors including crizotinib. ROS1 positivity is often clinically detected by fluorescence in situ hybridization (FISH), however ROS1 IHC can be used to screen samples prior to FISH confirmation of ROS1 status. The ROS1 (SP384) antibody detects ROS1 with high sensitivity, specificity, and consistency. Consistent interpretation of a ROS1 IHC assay between pathologists is important patient evaluation. Here we present inter-reader precision of 12 pathologists across 60 FFPE cases stained with ROS1 (SP384).
a9ded1e5ce5d75814730bb4caaf49419 Method
A retrospective cohort of 60 FFPE NSCLC cases stained with H&E, Rabbit Monoclonal Negative Control Ig, and ROS1 (SP384) were selected to represent positive, negative, and borderline ROS1 IHC status. Twelve practicing lung pathologists independently scored the cases as positive or negative around a cutoff of cytoplasm staining in > 30% tumor cells at a ≥2+ intensity level using Pathotrainer software (Pathomation bvba). Scoring was blinded to other readers and ROS1 status of the cases. Overall percent agreement (OPA), negative percent agreement (NPA), and positive percent agreement (PPA) were calculated in comparison to the group mode. Average overall percent agreement (AOPA), average positive agreement (APA), and average negative agreement (ANA) were calculated pairwise for each reader pair. Following independent assessment, participating pathologists conducted a discordant case review establishing consensus reads for all 60 cases and compared 44 cases to available FISH results.
4c3880bb027f159e801041b1021e88e8 Result
OPA of each of the 12 readers to the mode was 96.4% (95% CI 93.9-98.6) with PPA of 96.3% (95% CI 92.7-99.4) and NPA of 96.5% (95% CI 92.8-99.5). Pairwise AOPA between each of the 12 readers was 94.5% (95%CI 91.2-97.7) with APA 94.0% (95% CI 89.5-97.6) and ANA 95.0% (95%CI 91.2-97.9).
Consensus IHC scores were concordant with FISH 90.0% (40/44 cases).
8eea62084ca7e541d918e823422bd82e Conclusion
Inter-reader precision around a cutoff of >30% tumor cells with cytoplasmic staining at a ≥2+ intensity level was high in interpreting ROS1 (SP384) in NSCLC samples. Case review highlighted confirmation with FISH in questionable cases and staining patterns to be considered when interpreting ROS1 (SP384) IHC.
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