1366P - Association between the adverse events and serum concentrations of lorlatinib in patients with advanced ALK-positive lung cancer

Background

Lorlatinib is a third-generation anaplastic lymphoma kinase (ALK) inhibitor, has been the standard of care for untreated and previously treated patients with advanced ALK-positive non-small cell lung cancer (NSCLC). The common adverse events (AEs) of lorlatinib leading to drug discontinuation or dose reduction were hyperlipidemia, edema, and central nervous system (CNS)/ psychiatric disorders. The association between AEs and serum concentrations of lorlatinib remains unclear.

Methods

We retrospectively reviewed advanced ALK-positive NSCLC patients treated with lorlatinib between December 2018 and July 2022. The association between AEs and serum concentrations of lorlatinib was assessed at 28 days (± 14 days) after the initiation of lorlatinib using a high-performance liquid chromatography tandem mass spectrometry.

Results

Among 55 eligible patients, the median age was 54 years (range: 23–79) and the median number of treatment lines was 2 (range: 2-10). Most patients were female (29 [53%]) and performance status 0-1 (48 [87%]). Grade 3 or higher AEs occurred in 23 patients (42%) including hyperlipidemia in 18 (33%), edema in 5 (9%), and CNS/ psychiatric disorders in 4 (7%). Discontinuation or dose reduction was required in 21 patients (38%). Serum concentrations were measured in 36 patients (65%) and were significantly higher in the patients experiencing grade 3 or higher AEs than those without (462 ng/mL vs 177 ng/mL, p<0.01). On the other hand, there was no significant difference in progression-free survival (PFS) between the patients who had experienced the discontinuation or dose reduction within the first 6 months and those who had not (12.8M vs 5.2M, p=0.14).

Conclusions

The incidence of grade 3 or higher AEs with lorlatinib was associated with high serum concentrations at the first month of treatment. Drug discontinuation or dose reduction had no impact on PFS.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

T. Yoshida: Financial Interests, Personal and Institutional, Research Grant, Personal fees: Amgen, AstraZeneca, Ono, MSD, Novartis, Chugai, BMS; Financial Interests, Institutional, Research Grant: Takeda, Daiichi Sankyo, AbbVie; Financial Interests, Personal, Speaker’s Bureau, Personal fees: Taiho, Lilly, Roche, ArcherDX. Y. Matsumoto: Financial Interests, Institutional, Research Grant: National Cancer Center Research and Development Fund, Grant-in-Aid for Scientific Research on Innovative Areas, Hitachi, Ltd; Financial Interests, Personal and Institutional, Research Grant, Personal fees: Olympus; Financial Interests, Personal, Speaker’s Bureau, Personal fees: AstraZeneca, Novartis, Cook, Amco Inc, Thermo Fisher Scientific, Erbe Elektromedizin GmbH, Fujifilm, Chugai, Eli Lilly. Y. Shinno: Financial Interests, Personal, Speaker’s Bureau, Personal fees: BMS, Chugai, AstraZeneca, Eli Lilly; Financial Interests, Personal and Institutional, Research Grant, Personal fees: Ono; Financial Interests, Institutional, Research Grant: Janssen, Japan Clinical Research Operations K.K. Y. Okuma: Financial Interests, Institutional, Research Grant: Roche, AbbVie K.K; Financial Interests, Personal, Speaker’s Bureau, Personal fees: AstraZeneca, EIi Lilly K.K, Bristol Myers Squibb, Pfizer, Taiho Pharma Co. Ltd., AstraZeneca, Nippon, Boehringer Ingelheim, Chugai Pharma Co. Ltd., Ono Pharma Co. Ltd., Taiho Pharma Co. Ltd.. Y. Goto: Financial Interests, Institutional, Research Grant: AZK, AbbVie, Kyorin, Preferred Network; Financial Interests, Personal and Institutional, Research Grant, Personal fees: Pfizer, Eli Lilly, Bristol Myers Squibb, Ono, Novartis, Daiichi Sankyo; Financial Interests, Personal, Speaker’s Bureau, Personal fees: Chugai, Taiho, Boehringer Ingelheim, MSD, Merck, Thermo Fischer, AstraZeneca, Chugai, Guardant Health Inc., Illumina. H. Horinouchi: Financial Interests, Personal and Institutional, Research Grant, Personal fees: MSD, AstraZeneca, BMS, Ono, Chugai, Roche, Novartis; Financial Interests, Institutional, Research Grant: AbbVie, Merck Biophama, Daiichi Sankyo, Janssen, Genomic Health; Financial Interests, Personal, Speaker’s Bureau, Personal fees: Eli Lilly, Kyowa-Kirin. N. Yamamoto: Financial Interests, Personal and Institutional, Research Grant, Personal fees: Chugai, Eisai, Lilly, BMS, Pfizer, Boehringer Ingelheim, Ono Pharmaceutical Co., Ltd, Takeda, Otsuka; Financial Interests, Institutional, Research Grant: Taiho, Quintiles, Astellas, Novartis, Daiichi Sankyo, Kyowa-Hakko Kirin, Bayer, Janssen Pharma, MSD, Merck, GSK, Sumitomo Dainippon, Chiome Bioscience Inc., Carna Biosciences, Genmab, Shionogi; Financial Interests, Personal, Speaker’s Bureau, Personal fees: Sysmex, AstraZeneca, Cimic. Y. Ohe: Financial Interests, Personal and Institutional, Research Grant, Personal fees: AstraZeneca, Chugai, Eli Lilly, Ono, BMS, Kyorin, Pfizer, Taiho; Financial Interests, Institutional, Research Grant: Dainippon-Sumitomo, Novartis, Takeda, Kissei, Daiichi Sankyo, Janssen, Loxo; Financial Interests, Personal, Speaker’s Bureau, Personal fees: Boehringer Ingelheim, Bayer, MSD, Nippon Kayaku, Kyowa Hakko Kirin, Celltrion, Amgen, An Heart Tharapeutics Inc. All other authors have declared no conflicts of interest.