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Association details:
| Biomarker: | ALK rearrangement + TP53 mutation |
|---|---|
| Cancer: | Non Small Cell Lung Cancer |
| Drug: | Alecensa (alectinib) (ALK inhibitor) |
| Direction: | Resistant |
Evidence:
Source:
Title:
Final efficacy and safety data, and exploratory molecular profiling from the phase III ALUR study of alectinib versus chemotherapy in crizotinib-pretreated ALK-positive non-small-cell lung cancer
Published date:
01/15/2022
Excerpt:
CNS ORR was 66.7% with alectinib versus 0% with chemotherapy (P < 0.001). No new safety signals were seen. ALK rearrangement was identified in 69.5% (n = 41/59) of baseline plasma samples….Detection of mutant TP53 in baseline plasma resulted in numerically shorter PFS with alectinib (hazard ratio 1.88, 95% confidence interval 0.9-3.93)....Final efficacy data from ALUR confirmed the superior PFS, ORR and CNS ORR of alectinib versus chemotherapy in pretreated, advanced ALK-positive non-small-cell lung cancer. Alectinib prolonged PFS versus chemotherapy in patients with wild-type or mutant TP53; however, alectinib activity was considerably decreased in patients with mutant TP53.
DOI:
https://doi.org/10.1016/j.esmoop.2021.100333
Trial ID:
Source:
Title:
Proteasome inhibition overcomes ALK-TKI resistance in ALK-rearranged/TP53 mutant NSCLC via Noxa expression
Published date:
12/11/2020
Excerpt:
In 90 ALK-rearranged NSCLC patients who were treated with a selective ALK-TKI, alectinib, TP53 co-mutated patients showed significantly worse progression-free survival (PFS) than TP53 wild-type patients [median PFS, 11.7 months (95% CI, 6.3-not reached [NR]) vs. NR (23.6-NR); p=0.0008; hazard ratio, 0.33 (95% CI, 0.17-0.65)].
DOI:
10.1158/1078-0432.CCR-20-2853
