Abstract 1130P
Background
For pts with metastatic NSCLC and a sensitizing EGFR mutation, osi is standard treatment, either in first line (1L) or beyond (2L+, if T790M+). Limited osi efficacy data is available in relation to plasma trough levels, as well as elderly or those with low or high BMI.
Methods
Retrospective Dutch multicentre (two academic, one non-academic) study. Eligible: pts ≥18 years, with metastatic EGFR+ NSCLC regularly treated with osi. Start date of osi was used as index date, data was extracted from medical files. Primary endpoint: progression free survival (PFS). Secondary endpoint: overall survival (OS), objective response rate (ORR, RECIST v1.1) and disease control rate (DCR). Kaplan-Meier and multivariate Cox proportional hazard models were used to compare different subgroups for age, BMI and steady state plasma trough levels (Cmin,SS), measured <3 months (m) before disease progression (age [<70 / ≥70], BMI [<18.5 / 18.5 – 24.9 / 25.0 – 29.9 / >30] and plasma trough level [<149 / 149 – 259 / >259]).
Results
In total 294 pts were included: mean age 67 years (range = 29 – 87 years), mean BMI 25.3 (range = 17.6 – 67.1), 35% male, 90% Caucasian, 54% exon 19 deletion, 30% L858R, 17% other. Osi was given in 1L (n = 118, 40%), 2L (n = 134, 46%) or beyond (3L+, n=42, 14%). Median PFS was 14.6 m (95% CI = 10.2 – 20.0) (1L), 13.7 m (95% CI = 11.1 – 15.6) (2L) and 8.7 m (95% CI = 5.1 – 12.7) (3L+). ORR and DCR were similar in all lines (1L: 68% and 96%, 2L: 62% and 93% and 3L+: 69% and 91%). Pts ≥70 years at osi start achieved similar PFS and OS compared to pts <70 years (PFS: aHR = 0.93; 0.68 – 1.28; OS: aHR = 1.14; 0.77 – 1.68). Low BMI (<18.5) led to lower absolute effectiveness (PFS and OS), but not statistically significant, due to the low number of pts in the subgroup (n = 8). A high plasma trough concentration was associated with lower PFS (aHR = 1.92, 95% CI = 1.10 – 3.37).
Conclusions
PFS and OS with 1L osi were lower compared to those found in the FLAURA trial, while in 2L survival was slightly longer in daily practice. Age was not associated with PFS, while a low BMI and a high Cmin,SS may be correlated with worse treatment outcomes on osi.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
M.G.D. Veerman: Financial Interests, Personal, Other: Eli Lilly. R.H. Mathijssen: Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Servier; Other, Personal, Other, Patent pending: Pamgene; Financial Interests, Institutional, Other, Investigator-initiated research: Astellas, Bayer, Boehringer Ingelheim, Cristal Therapeutics, Pamgene, Pfizer, Novartis, Roche, Servier. A.C. Dingemans: Financial Interests, Institutional, Advisory Board: Roche, Sanofi, Amgen, Bayer, Boehringer Ingelheim; Financial Interests, Institutional, Invited Speaker: Takeda, Lilly, Jansen, Pfizer, AstraZeneca, Lilly, Amgen, Daiichi, Roche, Roche, JNJ, Mirati; Financial Interests, Institutional, Research Grant: Amgen; Non-Financial Interests, Other, Chair lung cancer group; EORTC; Non-Financial Interests, Member: IASCL, ASCO, AACR. V.C.G. Tjan-Heijnen: Financial Interests, Personal, Other, Honoraria: Novartis, Roche, Eli Lilly, AstraZeneca; Financial Interests, Personal, Advisory Board: Pfizer, Eli Lilly, Accord, Novartis; Financial Interests, Institutional, Other, Research funding: Roche, Eisai, Pfizer, Novartis, Eli Lilly, Daiichi Sankyo/AstraZeneca, Gilead. L. Hendriks: Financial Interests, Institutional, Advisory Board: BMS, Boehringer Ingelheim, Lilly, Takeda, Amgen, Pfizer; Financial Interests, Institutional, Advisory Board, one time also personal: Roche; Financial Interests, Institutional, Other, performing interviews at conference: Roche; Financial Interests, Personal, Other, mentorship with key opinion leaders funded by AstraZeneca: AstraZeneca; Financial Interests, Personal, Invited Speaker, for webinars: Medtalks; Financial Interests, Institutional, Invited Speaker: MSD, AstraZeneca, GSK, Novartis, Merck Serono, Roche, Takeda, Blueprint Medicines, Mirati, Janssen; Financial Interests, Personal, Other, travel support: Roche, BMS; Financial Interests, Personal, Invited Speaker, payment for post ASCO round table discussion: VJOncology; Financial Interests, Institutional, Invited Speaker, payment for post ESMO discussion: high5oncology; Financial Interests, Personal, Invited Speaker, payment for post ASCO/ESMO/WCLC presentations, educational committee member: Benecke; 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; Financial Interests, Institutional, Research Grant, for IIS (contract in negotiation): Takeda; Financial Interests, Institutional, Other, drug support for IIS (contract in negotiation): BeiGene; 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.