Progress on Lorlatinib – What's Next?
Lorlatinib is currently mainly used in the 2nd and later lines of treatment for non-small cell lung cancer (NSCLC) with ALK gene rearrangement. Clinical research is now focusing on the question of how to proceed with patients who experience disease progression during lorlatinib treatment in later lines of therapy. It seems that one of the options might actually be to do nothing – to continue with lorlatinib.
Retrospective Study
An international team of oncologists recently evaluated existing data from participants in a phase II clinical trial with lorlatinib, which started in early 2014 and is ongoing. The researchers analyzed data from 102 patients who initially responded to lorlatinib with at least disease stabilization for at least 6 weeks but subsequently experienced progression. In terms of therapy prior to lorlatinib, these were patients who had already been treated with crizotinib or at least one second-generation tyrosine kinase inhibitor (TKI) (ceritinib, alectinib, brigatinib, entrectinib).
One group in the study continued taking lorlatinib for more than 3 weeks despite disease progression, while the other group discontinued lorlatinib treatment after progression. These patients either were not treated further or switched to another TKI and/or underwent radiotherapy.
Prolonging Life and Preserving Its Quality
In terms of baseline clinicopathological characteristics, the group that continued with lorlatinib despite progression did not significantly differ from the group that discontinued treatment. As shown in the table, patients who continued with lorlatinib despite progression had longer overall survival (OS) than those who discontinued lorlatinib after progression. The difference was about 1 year for patients pre-treated with at least one second-generation TKI, and it was not yet possible to calculate for patients pre-treated with crizotinib because the number of deceased in this group was low. Furthermore, the quality of life analysis showed that it did not deteriorate at the expense of prolonged survival.
Table: Clinical Outcomes of Analyzed Groups
|
Patients pre-treated with crizotinib |
Patients pre-treated with ≥ 1 second-generation TKI |
|||
|
continuing |
not continuing |
continuing |
not continuing |
|
|
Number of people |
21 |
7 |
56 |
18 |
|
Duration of treatment in months (range) |
32.4 (4.6–41.9) |
12.5 (0.4–38.8) |
16.4 (3.7–43.2) |
7.7 (2.8–38.2) |
|
Duration of treatment after progression in months (range) |
11.8 (0.8–36.8) |
0.1 (0.0–0.3) |
5.7 (0.8–32.7) |
0.3 (0.0–0.6) |
|
Median OS in months (95% CI) |
N (N–N) |
24.4 (12.1–N) |
26.5 (18.7–35.5) |
14.7 (9.3–38.5) |
|
Median OS after progression in months (95% CI) |
N (21.4–N) |
8.0 (1.5–N) |
14.6 (11.2–19.2) |
5.3 (2.8–14.3) |
Note: CI – confidence interval, N – not reached.
Conclusion
This is still just a theoretical possibility, but the results of this retrospective study suggest that continuing with lorlatinib despite disease progression may be a suitable option for palliative treatment of the disease in some patients.
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Source: Ou S. H. I., Solomon B. J., Shaw A. T. et al. Continuation of lorlatinib in ALK-positive NSCLC beyond progressive disease. J Thorac Oncol 2022; 17 (4): 568–577, doi: 10.1016/j.jtho.2021.12.011.
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