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Continuation of Lorlatinib in ALK-Positive NSCLC Beyond Progressive Disease
Sai-Hong I Ou1, Benjamin J Solomon2, Alice T Shaw3
1Division of Hematology-Oncology, Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, California.
Introduction:
Lorlatinib, a potent, selective third-generation ALK tyrosine kinase inhibitor (TKI), exhibited overall and intracranial antitumor activity in patients with ALK-positive NSCLC.
Methods:
Retrospective analyses in the ongoing phase 2 trial (NCT01970865) investigated the clinical benefit of continuing lorlatinib beyond progressive disease (LBPD). Patients with previous crizotinib treatment as the only ALK TKI were group A (n = 28); those with at least one previous second-generation ALK TKIs were group B (n = 74). LBPD was defined as greater than 3 weeks of lorlatinib treatment after investigator-assessed progressive disease. Only patients with the best overall response of complete or partial response or stable disease were included.
Results:
There were no major differences in baseline characteristics between groups. The median duration of treatment for patients who continued LBPD was 32.4 months (group A) and 16.4 months (group B) versus 12.5 months (group A) and 7.7 months (group B) for patients who did not continue LBPD. The median overall survival in group A was not reached (NR) in patients who continued LBPD versus 24.4 months (95% confidence interval [CI]: 12.1-NR); group B's median was 26.5 months (95% CI: 18.7-35.5) in patients who continued LBPD versus 14.7 months (95% CI: 9.3-38.5) in patients who did not continue LBPD. The median overall survival postprogression for groups A and B was NR (95% CI: 21.4-NR) and 14.6 months (95% CI: 11.2-19.2) in patients who continued LBPD and 8.0 months (95% CI: 1.5-NR) versus 5.3 months (95% CI: 2.8-14.3) in patients who did not continue LBPD.
Conclusions:
Continuing LBPD is a viable treatment strategy for select patients with ALK-positive NSCLC who progressed on lorlatinib.
Insights
Continuing lorlatinib beyond progressive disease (LBPD) offers clinical benefit for select ALK-positive non-small cell lung cancer (NSCLC) patients. This strategy improved overall survival and treatment duration in retrospective analyses.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Lorlatinib is a third-generation ALK tyrosine kinase inhibitor (TKI) demonstrating efficacy in ALK-positive non-small cell lung cancer (NSCLC).
- Investigating treatment continuation after disease progression is crucial for optimizing patient outcomes.
Purpose of the Study:
- To evaluate the clinical benefit of continuing lorlatinib beyond progressive disease (LBPD) in patients with ALK-positive NSCLC.
- To compare outcomes between patients who continued LBPD and those who did not.
Main Methods:
- Retrospective analysis of a phase 2 trial (NCT01970865) involving patients with ALK-positive NSCLC.
- Patients were categorized into two groups based on prior ALK TKI treatment: crizotinib only (Group A) or at least one second-generation ALK TKI (Group B).
- LBPD was defined as continuing lorlatinib for over 3 weeks post-progression, including only patients with best overall response of CR, PR, or SD.
Main Results:
- Patients continuing LBPD had significantly longer treatment durations compared to those who discontinued.
- Median overall survival was not reached for Group A continuing LBPD versus 24.4 months for those who discontinued.
- Median overall survival for Group B continuing LBPD was 26.5 months versus 14.7 months for those who discontinued. Survival post-progression was also improved in patients continuing LBPD.
Conclusions:
- Continuing lorlatinib beyond progression is a viable strategy for select ALK-positive NSCLC patients.
- This approach demonstrates a clinical benefit, including improved survival outcomes.
- Further investigation into patient selection for LBPD is warranted.
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