Abstract 53P
Background
In the ph III FLAURA2 study (NCT04035486), 1L osi + platinum-pem chemotherapy (CTx) followed by osi + pem maintenance significantly improved PFS vs osi alone in pts with EGFRm aNSCLC. We report results from exploratory analyses characterising pem exposure.
Methods
Pts with treatment (tx)-naïve EGFRm (Ex19del/L858R) aNSCLC and WHO PS 0/1 (stable CNS metastases allowed) received osi 80 mg QD + pem and cis/carboplatin Q3W for 4 cycles (induction), followed by osi QD + pem Q3W (maintenance), or osi 80 mg QD alone until progression/discontinuation. Primary endpoint: PFS by investigator per RECIST v1.1. Exploratory post-hoc analyses by tx exposure in pts who received maintenance tx were performed. Data cutoff: 3 Apr 2023.
Results
211/279 pts (76%) randomised to the osi + CTx arm completed the planned 4 induction cycles; median duration of exposure (induction + maintenance) was: platinum CTx 2.8 mo, pem 8.3 mo and osi 22.3 mo. At start of maintenance (3 mo), 256/279 pts (92%) were ongoing tx (pem + osi or osi); the number of pts in pem maintenance exposure subgroups 3 – <9, 9 – <18 and ≥18 mo were 84 (30%), 49 (18%) and 83 (30%), respectively. Baseline characteristics were generally similar between pem exposure subgroups, with some differences (Table). Median PFS (95% CI) was 24.7 (19.6, NC), 27.6 (16.7, NC) and 30.6 (27.4, NC) mo in the 3 – <9, 9 – <18 and ≥18 mo subgroups, respectively. Among pts who received maintenance tx, ≥G3 AEs causally related to pem were reported in 16% pts during 3 – <9 mo and 10% during ≥9 mo tx; AEs leading to pem discontinuation were 17% and 10%, respectively.
Table 53P| Baseline characteristics | Pemetrexed maintenance exposure | ||
|---|---|---|---|
| 3 – <9 mo (n=84) | 9 – <18 mo (n=49) | ≥18 mo (n=83) | |
| Age, median (range), years | 63 (26, 82) | 60 (34, 81) | 59 (39, 80) |
| Male, n (%) | 29 (35) | 25 (51) | 31 (37) |
| Race, n (%) Asian White Other |
41 (49) 29 (35) 14 (17) |
35 (71) 10 (20) 4 (8) |
61 (73) 19 (23) 3 (4) |
| Smoking status, n (%) Never Current/former |
60 (71) 24 (29) |
33 (67) 16 (33) |
57 (69) 26 (31) |
| WHO PS, n (%)* 0 1 |
35 (42) 48 (57) |
19 (39) 30 (61) |
30 (36) 53 (64) |
| EGFR mutation, n (%) Exon 19 deletion L858R Both |
54 (64) 29 (35) 1 (1) |
29 (59) 20 (41) 0 |
51 (61) 31 (37) 1 (1) |
| Extra-thoracic metastases, n (%) | 38 (45) | 25 (51) | 53 (64) |
| CNS metastases, n (%) | 27 (32) | 21 (43) | 43 (52) |
| *One patient (in the 3 – <9 mo subgroup) had a WHO PS of 2 | |||
Conclusions
Median PFS was >24 mo across all 3 pem maintenance exposure subgroups, with a trend for longer PFS with longer pem tx; selection bias should be considered. Median duration of exposure was longer for osi vs pem, indicating continued osi tx post-pem discontinuation. Further research to assess pem maintenance duration and optimise benefit-risk will support personalised tx.
Clinical trial identification
NCT04035486; release date: 29/07/2019.
Editorial acknowledgement
The authors would like to acknowledge Clare McCleverty, PhD, (as contracted) of Ashfield MedComms, an Inizio company, for medical writing support that was funded by AstraZeneca.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
D. Planchard: Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Novartis, Roche, Pfizer, MSD Oncology, Celgene, BeiGene, Samsung, AbbVie, Janssen, Daiichi Sankyo/AstraZeneca, Pierre Fabre, Seagen, Gilead Sciences, Sanofi/Aventis, GSK, Miratti. K. Kobayashi: Financial Interests, Personal, Other, Grants: Zeria Pharmaceutical; Financial Interests, Personal, Other, Consulting fees: Daiichi Sankyo, UCB Japan; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Other: Co-inventor on Japanese patent # 7422498; Peptide inhibiting cell migration, cell invasion, and cancer metastasis. H. Mann: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. Y. Rukazenkov: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. C.K. Lee: Financial Interests, Personal, Other, Grants or contracts: Roche, Amgen, AstraZeneca, Merck KGaA; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Amgen, Janssen, GSK, Merck KGaA, Roche, Gilead, Novartis, Takeda, Boehringer Ingelheim, MSD, Glenmark; Financial Interests, Personal, Other, Travel support: AstraZeneca. N. Valdiviezo: Financial Interests, Personal, Other, Travel support: AstraZeneca. J.C. Yang: Financial Interests, Personal, Other, Grants or contracts: AstraZeneca, F. Hoffmann-La Roche; Financial Interests, Personal, Other, Travel support: Dizal Pharaceuticals, AstraZeneca, Takeda Oncology; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, AbbVie, Bayer, Boehringer Ingelheim, Daiichi Sankyo Inc, Eli Lilly, F. Hoffmann-La Roche, Gilead Sciences Inc, Janssen Pharmaceuticals, Merck KGaA, Merck Sharp & Dohme Corporation, Novartis, Pfizer, Regeneron Pharmaceuticals, Takeda On; Financial Interests, Personal, Other, Steering committee: Amgen, AstraZeneca, Bayer, Daiichi Sankyo Inc, Eli Lilly, Janssen Pharmaceuticals, Merck KGaA, Merck Sharp & Dohme Corporation, Takeda Oncology, Yuhan Pharmaceuticals, ArriVent, Dizal Pharmaceuticals, Black Diamond Therapeutics Inc. Numab Therapeutics AG; Financial Interests, Personal, Other, Coordinating PI: AstraZeneca, Merck Sharp & Dohme Corporation, Dizal Pharmaceuticals; Financial Interests, Personal, Other, Local PI: Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo Inc, Eli Lilly, F. Hoffmann-La Roche, Gilead Sciences Inc, Janssen Pharmaceuticals, Merck KGaA, Merck Sharp & Dohme Corporation, Novartis, Takeda Oncology, Yuhan Pharmaceuticals, ArriVent, Di; Financial Interests, Personal, Member: ASCO, ESMO, IASLC. D. Ghiorghiu: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. P.A. Jänne: Financial Interests, Personal, Other, Grants or contracts: AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company, Takeda Oncology, PUMA, Astellas Pharmaceuticals, Daiichi Sankyo; Financial Interests, Personal, Royalties: Post marketing royalties from DFCI owned intellectual property on EGFR mutations licensed to Lab Corp; Financial Interests, Personal, Advisory Board: AstraZeneca, Mirati Therapeutics, Boehringer-Ingelheim, Pfizer, Roche/Genentech, Chugai Pharmaceuticals, Eli Lilly and Company, Ignyta, Takeda Oncology, Novartis, Voronoi, SFJ Pharmaceuticals, Biocartis, LOXO Oncology, PUMA, Sanofi, Transcenta, Daiichi Sa; Financial Interests, Personal, Other, Co-inventor on a DFCI owned patent on EGFR mutations licensed to Lab Corp: Lab Corp. All other authors have declared no conflicts of interest.