Abstract
Objectives
This real-world analysis describes treatment patterns, sequencing and clinical effectiveness,
toxicities, and health utility outcomes in advanced-stage, incurable ALK-positive
NSCLC patients across five different ALK-TKIs.
Materials and Methods
Clinicodemographic, treatment, and toxicity data were collected retrospectively in
patients with advanced-stage ALK-positive NSCLC at Princess Margaret Cancer Centre.
Patient-reported symptoms, toxicities, and health utilities were collected prospectively.
Results
Of 148 ALK-positive NSCLC patients seen July 2009-May 2021, median age was 58.9 years;
84 (57%) were female; 112 (76%) never-smokers; 54 (47%) Asian and 40 (35%) white;
139 (94%) received at least one ALK-TKI: crizotinib (n = 74; 54%) and alectinib (n = 61; 44%) were administered mainly as first-line ALK-TKI,
ceritinib, brigatinib and lorlatinib were administered primarily after previous ALK-TKI
failure. Median overall survival (OS) was 54.0 months; 31 (21%) patients died within
two years of advanced-stage diagnosis. Treatment modifications were observed in 35
(47%) patients with crizotinib, 19 (61%) with ceritinib, 41 (39%) with alectinib,
9 (41%) with brigatinib and 8 (30%) with lorlatinib. Prevalence of dose modifications
and self-reported toxicities were higher with early versus later generation ALK-TKIs (P<.05). The presence of early treatment modification was not negatively associated
with progression-free survival (PFS) and OS analyses.
Conclusion
Serial ALK-TKI sequencing approaches are viable therapeutic options that can extend
quality of life and quantity-of-life, though a fifth of patients died within two years.
No best single sequencing approach could be determined. Clinically relevant toxicities
occurred across all ALK-TKIs. Treatment modifications due to toxicity may not necessarily
compromise outcomes, allowing multiple approaches to deal with ALK-TKI toxicities.
Keywords
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Article info
Publication history
Published online: September 23, 2022
Accepted:
September 15,
2022
Received in revised form:
September 7,
2022
Received:
July 14,
2022
Footnotes
Conflict of interest statement: On behalf of the co-authors of this manuscript we declare the following conflicts of interests:
Sabine Schmid: Advisory (institutional): Boehringer Ingelheim, MSD, BMS, Astra Zeneca; Research grants (institutional): BMS, Astra Zeneca, Janssen; Travel support: Takeda, Boehringer Ingelheim, MSD
Geoffrey Liu: Advisory or Institutional Grants: Boehringer Ingelheim, AstraZeneca, Bristol Myers Squibb, Merck, Takeda, Pfizer, Hoffman La Roche, Abbvie, EMD Serono, Eli Lilly.
Penelope Bradbury: Advisory Boards: Pfizer, Boehringer Ingelheim, Abbvie, Astra Zeneca (no financial remuneration); Honorarium: Merck, Eli Lilly.
Patrick Moriarty: Employee at Takeda Canada Inc; Hold Takeda Stock Options
The following authors declare no conflicts of interest: SC, SiC, MG, LZ, KH, KB, KK, DP, BG, RR, WX, FS, AS, NL.
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