Abstract 88P
Background
Interstitial lung disease (ILD) and pneumonitis are known adverse events (AEs) with tyrosine kinase inhibitors (TKIs) used to treat ALK+ NSCLC, including brigatinib. In brigatinib clinical trials, pulmonary AEs (eg, ILD, pneumonitis, dyspnea, hypoxia) occurring within 14 days of starting brigatinib were termed early-onset pulmonary events (EOPEs). A step-up dosing regimen for brigatinib (180 mg QD with a 7-day lead-in at 90 mg QD) was implemented to minimize EOPE occurrence. In patients (pts) with advanced NSCLC, symptoms of drug-related pulmonary AEs may be similar to those of the underlying cancer and other lung diseases, making it challenging to ascribe causality. This post-authorization safety study evaluated EOPE rates with brigatinib in a real-world setting.
Methods
This prospective, observational, single-arm study conducted at 29 sites across Europe followed adults with advanced ALK+ NSCLC during the first 42 days of brigatinib monotherapy initiation. Pulmonary events occurring on days 1 to 15 post brigatinib initiation were AEs of special interest (AESIs). An independent adjudication committee (AC) of 5 physicians with expertise in pulmonary medicine, radiology, and thoracic oncology reviewed AESIs to determine if they met all of the following EOPE criteria: (1) signs/symptoms began within 14 days of starting brigatinib; (2) evidence of a pneumonitis-like process supported by imaging or pathology; and (3) other etiology deemed unlikely.
Results
Of 98 enrolled pts (median age: 59.5 y; 50% female), 88 (90%) received brigatinib as first-line TKI. All 10 pts with prior TKI treatment received prior alectinib; 4 also had prior crizotinib (3 before and 1 after alectinib), and 2 had prior lorlatinib (both after alectinib). Most pts (79%) started brigatinib at 90 mg QD and transitioned to 180 mg QD. Median relative dose intensity was 99.4%. Eleven AESIs were reviewed by the AC, with none confirmed as EOPEs.
Conclusions
In this real-world study, most pts (79%) received brigatinib at doses consistent with recommended step-up dosing. There were no confirmed EOPEs after review by the independent AC. Inclusion of the AC may provide a more accurate representation of EOPE incidence than previous studies.
Editorial acknowledgement
Medical writing support provided by Lela Creutz, PhD, of Peloton Advantage, LLC, an OPEN Health company.
Legal entity responsible for the study
Takeda Development Center Americas, Inc.
Funding
Takeda Development Center Americas, Inc.
Disclosure
M.J. Hochmair: Financial Interests, Personal, Advisory Board: Roche, MSD, Böhringer Ingelheim, BMS, Takeda, Lilly. G. Stewart: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Sanofi, Regeneron, AstraZeneca, Takeda; Financial Interests, Personal, Other, Honoraria and meeting support: Takeda, Sanofi, Bristol Myers Squibb, AstraZeneca. M. Rauter: Financial Interests, Personal, Other, Meeting support and honoraria: Amgen, AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme, Janssen, Mirati, Roche, Sanofi, Takeda. B. Khokhar, R. Gounden, Y. Yin, R. Fram: Financial Interests, Personal, Full or part-time Employment: Takeda. T. Egenod: Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, Takeda, Roche. All other authors have declared no conflicts of interest.