Abstract 1347P
Background
Osi is designed to have better central nervous system (CNS) efficacy than other epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). However, 21% and 24% of pts treated in 1st or 2nd line develop CNS progression, mainly consisting of BM. A possible reason may be pharmacological failure of osi, due to low Cmin,SS and intracranial levels. However, data on osi Cmin,SS and BM related outcomes in Caucasians is lacking.
Methods
Retrospective study in three Dutch hospitals, collecting osi Cmin,SS from pts treated with osi 80 mg once daily for EGFR+ aNSCLC. Pts with parenchymal BM at start of osi were allocated to the BM-cohort and those without known BM to the no-known-BM-cohort. Pts were further allocated into subgroups based on osi Cmin,SS (low, middle or high). The primary outcome in both cohorts was cumulative incidence of BM development and progression.
Results
173 pts were included, 28% had BM at osimertinib initiation (BM-cohort). In both cohorts, most pts were female (71% BM-cohort and 69% no known BM-cohort) and approximately half of the pts received osi in 2nd line (49% BM-cohort and 51% no known BM-cohort). Median follow-up was 22.8 months and at data cut-off 39% of pts still used osi without progression of BM. In the BM-cohort, 18 out of 49 pts (37%) experienced BM progression. Competing risk analysis showed a cumulative incidence of BM progression of 20% (95% CI 2.6 – 49.0), 31% (95% CI 10.6 – 53.9) and 31% (95% CI 10.8 – 54.5) after 12 months for the Cmin,SS low, middle and high subgroups respectively and 20% (95% CI 2.6 – 49.0), 52% (95% CI 23.8 – 74.2) and 57% (95% CI 24.9 – 79.7) after 20 months for the corresponding subgroups. In the no-known-BM-cohort, 4% developed BM during osi and no differences were found between the Cmin,SS-subgroups.
Conclusions
This study suggests no relationship between plasma blood osi trough levels (Cmin,SS) and cumulative incidence of BM development and progression in pts with EGFR+ aNSCLC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
L.E.L. Hendriks.
Funding
Has not received any funding.
Disclosure
R.H. Mathijssen: Financial Interests, Institutional, Research Grant, Investigator-initiated research: Astellas, Bayer, Cristal Therapeutics, Pfizer, Roche, Sanofi, Servier, Boehringer Ingelheim, Novartis; Financial Interests, Institutional, Coordinating PI: Pamgene. V. Tjan-Heijnen: Financial Interests, Personal, Advisory Board: E Lilly, AstraZeneca, Novartis; Financial Interests, Institutional, Research Grant: E Lilly, Novartis, Pfizer, AstraZeneca, Roche, Gilead. E.F. Smit: Financial Interests, Institutional, Advisory Board: AstraZeneca, Daiichi Sankyo, MSD, Boehringer Ingelheim, Roche, Eli Lilly, Takeda, Sanofi, Janssen, BMS; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Merck Seranno; Financial Interests, Institutional, Other, DSMB member: DSI; Financial Interests, Institutional, Local PI: Pfizer, AZ, Genmab, DSI, Sanofi. A-M.C. Dingemans: Financial Interests, Institutional, Advisory Board: Roche, Sanofi, Amgen, Bayer, Boehringer Ingelheim; Financial Interests, Institutional, Invited Speaker: Takeda, Lilly, Jansen, Pfizer, AstraZeneca; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Local PI: Lilly, Amgen, Daiichi, JNJ, Mirati; Financial Interests, Institutional, Coordinating PI: Roche; Financial Interests, Institutional, Steering Committee Member: Roche; Non-Financial Interests, Other, Chair EORTC lung cancer group: EORTC; Non-Financial Interests, Member: IASCL, ASCO, AACR. L. Hendriks: Financial Interests, Institutional, Advisory Board: Amgen, Boehringer Ingelheim, Lilly, Novartis, Pfizer, Takeda, BMS, Merck, Janssen, MSD; Financial Interests, Personal, Other, mentorship with key opinion leaders funded by AstraZeneca: AstraZeneca; Financial Interests, Institutional, Invited Speaker, for educational webinar: AstraZeneca, Lilly; Financial Interests, Institutional, Invited Speaker, educational webinar/interview: Bayer; Financial Interests, Institutional, Invited Speaker, educationals: MSD; Financial Interests, Personal, Invited Speaker, for webinars: Medtalks; Financial Interests, Institutional, Advisory Board, one time also personal: Roche; Financial Interests, Institutional, Other, performing interviews at conference: Roche; Financial Interests, Personal, Other, travel support: Roche; Financial Interests, Institutional, Other, podcast on brain metastases: Takeda; Financial Interests, Personal, Invited Speaker, payment for post ASCO round table discussion: VJOncology; Financial Interests, Personal, Invited Speaker, payment for post ASCO/ESMO/WCLC presentations, educational committee member: Benecke; Financial Interests, Institutional, Invited Speaker, payment for post ESMO/ASCO discussion: high5oncology; Financial Interests, Institutional, Other, educational webinar: Janssen; Financial Interests, Personal, Other, member of the committee that revised these guidelines: Dutch guidelines NSCLC, brain metastases and leptomeningeal metastases; Financial Interests, Institutional, Research Grant, for IIS: Roche, Boehringer Ingelheim, AstraZeneca, Takeda; Financial Interests, Institutional, Local PI: AstraZeneca, GSK, Novartis, Merck Serono, Roche, Takeda, Blueprint Medicines, Mirati, AbbVie, MSD, Gilead; Financial Interests, Institutional, Research Grant, donation for health care improvement project: Merck; Financial Interests, Institutional, Research Grant, funding for healthcare improvement project: Pfizer; Non-Financial Interests, Other, Chair metastatic NSCLC for lung cancer group: EORTC; Non-Financial Interests, Other, secretary NVALT studies foundation: NVALT. All other authors have declared no conflicts of interest.
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