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Treatment Patterns and Clinical Outcomes Among Patients With ROS1-rearranged Non-small-cell Lung Cancer Progressing
Andrea De Giglio1, Giuseppe Lamberti2, Francesco Facchinetti3
1Medical Oncology, Santa Maria della Misericordia Hospital, University of Perugia, Piazzale Menghini, Perugia, Italy.
Background:
ROS1 rearrangements define a subset of non-small-cell lung cancers (NSCLCs) that are susceptible to therapeutic ROS1 kinase inhibition. Despite the fact that most patients initially respond to the first-generation ROS1 tyrosine kinase inhibitor (TKI) crizotinib, relapse invariably occurs, and therapeutic options upon disease progression are limited.
Patients And Methods:
We conducted a multicenter study of patients with ROS1-rearranged NSCLC who progressed on ROS1 TKIs and examined the clinical outcomes based on the post-progression treatment approaches.
Results:
Among 29 patients with ROS1-rearrangement who received at least 1 ROS1 inhibitor, the median age was 51 years (range, 30-80 years), 70.8% of patients were female, and 68.9% were never-smokers. Upon progression to the first TKI, 11 patients (37.9%) received treatment with TKIs beyond progression. The median second progression-free survival to TKIs in patents treated beyond progression was 5.5 months (95% confidence interval [CI], 4.1-9.1 months), whereas the post-progression survival was 21.0 months (95% CI, 5.5 months-not reached [NR]). Eleven (37.9%) patients received a sequential treatment with lorlatinib ROS1 TKIs following a first generation ROS1 TKI. The overall response rate, median progression-free survival, and median overall survival (OS) to next-generation TKIs were 41.7% (95% CI, 15.2%-72.3%), 12.7 months (95% CI, 8.5 months-NR), and 17.0 months (95% CI, 15.8 months-NR), respectively. Patients treated with sequential ROS1 TKIs had a significantly longer median OS compared with those who were not (NR vs. 16.1 months; hazard ratio, 0.26; 95% CI, 0.10-0.78; P = .017).
Conclusion:
In this study, we reported that a subset of patients with ROS1-rearranged NSCLC may benefit from treatment with TKIs beyond progression and that sequential treatment with crizotinib followed by lorlatinib is associated with improved OS in patients with ROS1-rearranged NSCLC.
Insights
Patients with ROS1-rearranged non-small-cell lung cancer (NSCLC) who progress on initial tyrosine kinase inhibitors (TKIs) may benefit from continued TKI therapy. Sequential treatment with crizotinib then lorlatinib improved overall survival in this patient group.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- ROS1 rearrangements identify a specific non-small-cell lung cancer (NSCLC) subtype responsive to ROS1 kinase inhibitors.
- While initial treatment with crizotinib is effective, acquired resistance leads to disease progression and limited subsequent therapeutic options.
Purpose of the Study:
- To evaluate clinical outcomes in patients with ROS1-rearranged NSCLC who progressed on ROS1 tyrosine kinase inhibitors (TKIs).
- To assess the efficacy of different post-progression treatment strategies, including TKIs beyond progression and sequential TKI therapy.
Main Methods:
- A multicenter study involving 29 patients with ROS1-rearranged NSCLC who received at least one ROS1 inhibitor.
- Analysis of treatment approaches after progression on first-generation TKIs, comparing outcomes for patients treated beyond progression versus those who were not.
- Evaluation of sequential treatment with lorlatinib following first-generation TKIs.
Main Results:
- Among 29 patients, 11 (37.9%) received TKIs beyond progression, with a median second progression-free survival of 5.5 months.
- Eleven patients (37.9%) received sequential lorlatinib after a first-generation TKI, achieving an overall response rate of 41.7% and median overall survival of 17.0 months.
- Patients receiving sequential ROS1 TKIs demonstrated significantly longer median overall survival (not reached vs. 16.1 months) compared to those who did not.
Conclusions:
- A subset of patients with ROS1-rearranged NSCLC may benefit from continued treatment with TKIs beyond initial progression.
- Sequential treatment with crizotinib followed by lorlatinib is associated with improved overall survival in patients with ROS1-rearranged NSCLC.
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