Abstract 3614
Background
The oral tyrosine kinase inhibitor (TKI) crizotinib is approved for the treatment of pts with anaplastic lymphoma kinase (ALK)+ advanced NSCLC. Here we report safety results for pts who were treated with crizotinib for longer than 1 year (y) in PROFILE 1005, the largest clinical trial to date of an ALK TKI in ALK+ advanced NSCLC.
Methods
The PROFILE 1005 study (NCT00932451) was a single-arm phase 2 trial of crizotinib (250 mg twice daily; continuously) conducted at multiple centers. The study enrolled pts with ALK+ NSCLC who had failed ≥1 line of systemic treatment for locally advanced/metastatic disease. The co-primary endpoints were safety and objective response rate.
Results
A total of 1066 pts were treated; 240 and 248 pts were treated for 1–2 y and >2 y, respectively. Treatment-related adverse events (TRAEs) are summarized by treatment duration subgroup in the table. Most common TRAEs of any grade in the 1–2 y and >2 y subgroups, respectively, were vision disorder (65.8% and 69.4%), nausea (57.5% and 58.1%), diarrhea (54.2% and 61.3%), vomiting (49.6% and 46.4%) and edema (47.1% and 60.1%). The most common grade 3/4 TRAE in both subgroups was neutropenia (17.1% and 23.0%). Two grade 5 TRAEs (interstitial lung disease [n = 1] and cardiac arrest [n = 1; for which other factors could not be excluded]) were reported in the >2 y subgroup; no grade 5 TRAEs were reported in the 1–2 y subgroup. Selected TRAEs of interest based on prior experience with crizotinib included the following, reported in the 1–2 y and >2 y subgroups, respectively: elevated transaminases (35.4% and 37.1%), hepatotoxicity (1.3% and 1.2%), interstitial lung disease (2.1% and 2.4%), ECG QT prolonged (2.5% and 4.8%), bradycardia (13.3% and 16.5%), and renal cysts (2.1% and 7.7%).Table: 1397P
| Treatment duration subgroup | |||
|---|---|---|---|
| n (%) | 1–2 y (n = 240) | >2y (n = 248) | Overall (n = 1066) |
| Pts with TRAEs | 239 (99.6) | 247 (99.6) | 1022 (95.9) |
| Pts with serious TRAEs | 23 (9.6) | 34 (13.7) | 119 (11.2) |
| Pts with grade 3 or 4 TRAEs | 104 (43.3) | 114 (46.0) | 425 (39.9) |
| Pts with temporary discontinuation due to TRAEs | 87 (36.3) | 103 (41.5) | 332 (31.1) |
| Pts with dose reductions due to TRAEs | 54 (22.5) | 56 (22.6) | 195 (18.3) |
| Pts permanently discontinued treatment due to TRAEs | 2 (0.8) | 4 (1.6) | 60 (5.6) |
Conclusions
No new major safety signals were observed. The long-term safety profile was consistent with the known safety profile of crizotinib.
Clinical trial identification
Legal entity responsible for the study
Pfizer, Inc.
Funding
Pfizer.
Editorial Acknowledgement
Medical writing support was provided by Jade Drummond and Brian Szente of inScience Communications, Springer Healthcare (Chester, UK and Philadelphia, PA, US), and was funded by Pfizer.
Disclosure
M-J. Ahn: Membership of an advisory board or board of directors: AstraZeneca, Lilly, Lyzz. S-H.I. Ou: Membership of an advisory board or board of directors: TP Therapeutics; Corporate sponsored research: Pfizer, AstraZeneca, Roche/Genentech, Takeda/Ariad, Ignyta, TP Therapeutics, BluePrint Medicines; Honorarium: Pfizer, Roche/Genentech, AstraZeneca, Takeda/Ariad. A.T. Shaw: Membership of an advisory board or board of directors: Blueprint Medicines, KSQ Therapeutics; Consulting or honoraria: Pfizer, Novartis, Genentech, Roche, Takeda, Ariad, Ignyta, Loxo, Blueprint, Natera, Foundation Medicine, EMD Serono. S. Lanzalone, A. Polli, K.D. Wilner: Stock ownership and employment: Pfizer. All other authors have declared no conflicts of interest.