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Q. Guo
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P3.03 - Chemotherapy/Targeted Therapy (ID 719)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.03-029 - ROS1 Alterations in Lung Adenocarcinoma: The Prognostic Role of Rearrangement and Copy Number Variation (ID 10400)
09:30 - 09:30 | Author(s): Q. Guo
- Abstract
Background:
ROS1 rearrangements define a distinct molecular subset of lung adenocarcinoma and patients (pts) experience significant improvements with oncogene-directed therapies. Break-apart/Split Fluorescence in situ hybridization (FISH) is a commonly used detection method for rearranged genes as well as the copy number variation (CNV). Based upon FISH, we aimed to thoroughly evaluate the prognostic role of ROS1 alterations in lung adenocarcinoma.
Method:
Between 1997 and 2016, 634 pts with complete FISH test data were enrolled and followed for outcome research. According to ratios of separated signals, ROS1 rearrangement status were dichotomized into positive and negative. Due to combinative patterns of the signals, positive ones were divided into typical (separation), atypical (single 3' signal) and rare patterns (single 5' signal), and CNV were divided into normal, amplification and deletion.
Result:
ROS1 rearrangement was present in 24 (3.8%) pts, including 17 (2.7%) typical or atypical patterns and 7 (1.1%) rare patterns. ROS1 rearranged pts confer sensitivity to treatment with ALK/ROS1/MET inhibitor crizotinib as the overall response rate (ORR: CR+PR) is 37.5% and the overall disease control rate (DCR: CR+PR+SD) is 75.0%; for 1st line therapy, these rates are 50.0% and 83.3%, respectively. However, the ORR and DCR were dramatically decreased in 2nd or 3rd line therapy as 25.0% and 25.0%. Overall survival rates differ among three kinds of rearranged patterns; rare pattern pts tend to have the worst prognosis. Multivariate Cox regression analysis indicated that ROS1 rearrangement (hazard ratio [HR], 0.49) was significantly associated with improved overall survival (OS) while disease free survival (DFS) was equivocal (HR=0.66; p=0.22), and CNV was not an independent prognostic factor for both OS and DFS. ROS1-negative pts had worse fatigue and lung cancer symptoms than positive ones, while CNV did not predict recent QOL. Younger age (<60 years), female gender, non-smoker and advanced stage (IIIb-IV) were significant indicators for ROS1 rearrangement.
Conclusion:
ROS1 rearrangement confers favor OS and QOL in lung adenocarcinoma pts and crizotinib induced preferable clinical remission, while CNV showed no exact implications, which might only act as an minor aspect of genetic heterogeneity in tumor cells. Therefore, our results highlight the importance of screening for ROS1 rearrangement in pts with lung adenocarcinoma, which should help to prolong pts’ survival time and maintain or improve QOL.
