Later-Line Treatment with Lorlatinib in ALK- and ROS1-Rearrangement-Positive NSCLC: A Retrospective, Multicenter Analysis
Abstract
:1. Introduction
2. Results
2.1. Patient Characteristics
2.2. Efficacy
2.2.1. ALK-Positive Patients
- Efficacy after only 1 s generation TKI and ≥2 s generation TKIs:
- Efficacy after alectinib and brigatinib:
2.2.2. ROS1-Positive Patients
2.3. Tolerability
3. Discussion
4. Materials and Methods
Statistical Analysis
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Patient Characteristics | ALK(+) | ROS(+) |
---|---|---|
N (%) | 37 (72.5%) | 14 (27.5%) |
Age at metastatic diagnosis | ||
Mean age (SD) at met. diagnosis | 53.0 (13.4) | 55.4 (16.4) |
Range | 29–77 | 26–82 |
Sex | ||
Female | 24 (64.9%) | 7 (50.0%) |
Male | 13 (35.1%) | 7 (50.0%) |
Smoking history | ||
Current | 3 (8.1%) | 1 (7.1%) |
Former | 11 (29.7%) | 5 (35.7%) |
Never-Smoker | 23 (62.2%) | 8 (57.1%) |
Stage at initial diagnosis | ||
Stage I | 1 (2.7%) | 1 (7.1%) |
Stage II | 0 (0%) | 0 (0%) |
Stage IIIa | 3 (8.1%) | 0 (0%) |
Stage IIIb | 3 (8.1%) | 0 (0%) |
Stage IV | 30 (81.1%) | 13 (92.9%) |
Brain metastasis at diagnosis | ||
Yes | 19 (51.4%) | 9 (64.3%) |
No | 15 (40.5%) | 4 (28.6%) |
Unknown | 3 (8.1%) | 1 (7.1%) |
Method of detection | ||
IHC | 13 (35.1%) | 5 (35.7%) |
FISH | 17 (45.9%) | 7 (50.0%) |
NGS | 1 (2.7%) | 0 (0%) |
More than 1 | 6 (16.2%) | 2 (14.3%) |
Histology | ||
Adenocarcinoma | 35 (94.6%) | 13 (92.8) |
Adeno-squamous | 1 (2.7%) | 1 (7.1%) |
Squamous-cell carcinoma | 1 (2.7%) | 0 (0%) |
Prior lines of therapy | ||
2 lines | 3 (8.1%) | 6 (42.9%) |
3 lines | 11 (29.7%) | 2 (14.3%) |
4 lines | 14 (37.8%) | 1 (7.1%) |
5 lines | 8 (21.6%) | 4 (28.6%) |
6 lines | 0 (0%) | 1 (7.1%) |
9 lines | 1 (2.7%) | 0 (0%) |
Prior lines of TKI | ||
1 lines | 10 (27.0%) | 11 (78.6%) |
2 lines | 13 (35.1%) | 3 (21.4%) |
3 lines | 13 (35.1%) | 0 (0%) |
4 lines | 1 (2.7%) | 0 (0%) |
Prior lines in detail | ||
Alectinib | 14 (37.8%) | 0 (0%) |
Brigatinib | 27 (73.0%) | 0 (0%) |
Ceritinib | 21 (56.8%) | 3 (21.4%) |
Crizotinib | 25 (67.6%) | 14 (100%) |
At least one Chemotherapy | 10 (27.0%) | 8 (57.1%) |
Efficacy Results of ALK Positive Patients | ||||||
Results | Overall | 1 Prior TKI | 2 Prior TKI | ≥3 Prior TKI | Only One 2nd Gen TKI | ≥Two 2nd Gen TKI |
N (%) | 37 (100%) | 10 (27.0%) | 13 (35.1%) | 14 (37.8%) | 20 (54.1%) | 17 (45.9%) |
ORR1 | 43.2% (27.1; 60.5) | 40.0% (12.2; 73.8) | 53.8% (25.1; 80.8) | 35.7% (12.8; 64.9) | 50.0% (27.2; 72.8) | 35.3% (14.2; 61.7) |
DCR1 | 56.8% (39.5; 72.9) | 60.0% (26.2; 87.8) | 69.2% (38.6; 90.9) | 42.9% (17.7; 71.1) | 60.0% (36.1; 80.9) | 52.9% (27.8; 77.0) |
CR | 1 (2.7%) | 0 (0%) | 0 (0%) | 1 (7.1%) | 0 (0.0%) | 1 (5.9%) |
PR | 15(40.5%) | 4 (40.0%) | 7 (53.8%) | 4 (28.6%) | 10 (50.0%) | 5 (29.4%) |
SD | 5 (13.5%) | 2 (20.0%) | 2 (15.4%) | 1 (7.1%) | 3 (10.0%) | 3 (17.6%) |
PD | 16 (43.2) | 4 (40.0%) | 4 (30.8%) | 8 (57.1%) | 8 (40.0%) | 8 (47.1%) |
Median DoT2 | 4.4 (1.3; 7.6) | 4.4 (0.5; 8.2) | NR | 3.0 (1.8; 4.2) | 4.4 (1.1; 7.7) | 4.4 (0.2; 8.6) |
Median OS2 (since lorla start) | 10.2 (3.6; 16.8) | 6.4 (3.9; 9.0) | 31.2 (NR) | 7.1 (0.0; 20.2) | 7.9 (0.0; 29.7) | 10.2 (4.1; 16.2) |
Median OS2 (since advanced diagnosis) | 41.8 (34.1; 49.5) | 28.3 (11.9; 44.8) | 66.5 (NR) | 40.6 (30.5–50.8) | 39.2 (21.7; 56.7) | 43.4 (30.9; 55.9) |
Risk analysis of the efficacy data of ALK positive patients | ||||||
Risk Analysis3 | Maturity | 3-Months | 6-Months | 12-Months | 2-Years | 5-Years |
DoT rate | 70.3% | 62.2% | 45.9% | 31.7% | NR | NR |
OS rate (since lorla start) | 67.6% | 73.0% | 62.2% | 45.4% | 35.1% | NR |
OS rate (since advanced diagnosis) | 67.6% | 100% | 100% | 86.5% | 70.3% | 33.3% |
Efficacy results of ROS1 positive patients | ||||||
Results | Overall | 1 Prior TKI | 2 Prior TKI | |||
N (%) | 14 (100%) | 11 (78.6%) | 3 (21.4%) | |||
ORR 4 | 85.7% (57.2; 98.2) | 90.9% (58.7; 99.8) | 66.7% (0.9; 99.2) | |||
DCR 1 | 92.9% (66.1; 99.8) | 100% (71.5; 100) | 69.2% (0.9; 99.2) | |||
CR | 2 | 2 | 0 | |||
PR | 10 | 8 | 2 | |||
SD | 1 | 1 | 0 | |||
PD | 1 | 0 | 1 | |||
Median DoT 5 | 12.2 (0.0; 29.5) | 25.0 (8.0; 42.1) | 7.0 (0.0; 16.6) | |||
Median OS 5 (since lorla start) | 20.0 (NR) | 17.6 (NR) | 24.4 (3.1; 45.6) | |||
Median OS 5 (since advanced diagnosis) | 40.1 (NR) | 39.2 (NR) | 46.3 (38.7; 105.9) | |||
Risk analysis of the efficacy data of ROS1 positive patients | ||||||
Risk Analysis 6 | Maturity | 3-Months | 6-Months | 12-Months | 2-Years | 5-Years |
DoT rate (SD) | 57.1% | 78.6% | 78.6% | 50.0% | 49.0% | NR |
OS rate (SD) (since lorla start) | 42.9% | 92.9% | 92.9% | 61.4% | 50.8% | NR |
OS rate (SD) (since advanced diagnosis) | 42.9% | 100% | 100% | 100% | 92.9% | 58.8% |
Adverse Events | Grade 1 | Grade 2 | Grade 3 | Grade 4 |
---|---|---|---|---|
N = 51 | N (%) | N (%) | N (%) | N (%) |
Hyperlipidemia | 8 (16%) | 8 (16%) | 4 (8%) | 5 (10%) |
Hypercholesterolemia | 6 (12%) | 4 (8%) | 2 (4%) | 2 (4%) |
Hypertriglyceridemia | 2 (4%) | 4 (8%) | 2 (4%) | 3 (6%) |
Peripheral Edema | 5 (10%) | 1 (2%) | 1 (2%) | |
Cognitive Effects | 1 (2%) | 2 (4%) | ||
Diarrhea | 1 (2%) | 2 (4%) | ||
Arthralgia | 1 (2%) | |||
Fatigue | 1 (2%) | |||
Peripheral Neuropathy | 1 (2%) | |||
Other | 3 (6%) | 2 (4%) | ||
Bloating | 1 (2%) | |||
Muscle Weakness | 1 (2%) | |||
Myalgia | 1 (2%) | |||
Pneumonitis | 1 (2%) | |||
Thrombosis | 1 (2%) |
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Hochmair, M.J.; Fabikan, H.; Illini, O.; Weinlinger, C.; Setinek, U.; Krenbek, D.; Prosch, H.; Rauter, M.; Schumacher, M.; Wöll, E.; et al. Later-Line Treatment with Lorlatinib in ALK- and ROS1-Rearrangement-Positive NSCLC: A Retrospective, Multicenter Analysis. Pharmaceuticals 2020, 13, 371. https://doi.org/10.3390/ph13110371
Hochmair MJ, Fabikan H, Illini O, Weinlinger C, Setinek U, Krenbek D, Prosch H, Rauter M, Schumacher M, Wöll E, et al. Later-Line Treatment with Lorlatinib in ALK- and ROS1-Rearrangement-Positive NSCLC: A Retrospective, Multicenter Analysis. Pharmaceuticals. 2020; 13(11):371. https://doi.org/10.3390/ph13110371
Chicago/Turabian StyleHochmair, Maximilian J., Hannah Fabikan, Oliver Illini, Christoph Weinlinger, Ulrike Setinek, Dagmar Krenbek, Helmut Prosch, Markus Rauter, Michael Schumacher, Ewald Wöll, and et al. 2020. "Later-Line Treatment with Lorlatinib in ALK- and ROS1-Rearrangement-Positive NSCLC: A Retrospective, Multicenter Analysis" Pharmaceuticals 13, no. 11: 371. https://doi.org/10.3390/ph13110371