1347P - Peripheral osimertinib (osi) plasma trough concentration (Cmin,SS) as surrogate parameter for development and progression of brain metastasis (BM) in patients (pts) with EGFR+ advanced non-small cell lung cancer (aNSCLC)

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 1^st or 2^nd line develop CNS progression, mainly consisting of BM. A possible reason may be pharmacological failure of osi, due to low C_min,SS and intracranial levels. However, data on osi C_min,SS and BM related outcomes in Caucasians is lacking.

Methods

Retrospective study in three Dutch hospitals, collecting osi C_min,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 C_min,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 2^nd 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 C_min,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 C_min,SS-subgroups.

Conclusions

This study suggests no relationship between plasma blood osi trough levels (C_min,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.