568P - First-line (1L) osimertinib + platinum-pemetrexed in EGFR-mutated (EGFRm) advanced NSCLC: Updated FLAURA2 safety run-in (SRI) results

Background

Osimertinib (osi), a third-generation, CNS-active EGFR-TKI, is the preferred 1L treatment for EGFRm advanced NSCLC, based on significant clinical benefit in the FLAURA study; however, most patients (pts) will develop disease progression. FLAURA2 (NCT04035486) is a global, phase III, open-label, randomised study of 1L osi + platinum-pemetrexed (pem) vs osi monotherapy in EGFRm advanced NSCLC. The FLAURA2 SRI phase assessed the safety/tolerability of the combination prior to the randomised period. We report final data following 3-years additional follow-up (previous data cut-off [DCO]: 19 Feb 2020).

Methods

Overall, 30 pts (≥18 years; ≥20 years Japan) with locally advanced/metastatic NSCLC received oral osi 80 mg once daily (QD) + either intravenous cisplatin 75 mg/m² or carboplatin AUC5 + pem 500 mg/m² every 3 weeks (Q3W) for 4 cycles, then maintenance osi (80 mg QD) + pem 500 mg/m² (Q3W) until progression/discontinuation. SRI primary endpoint: safety; secondary endpoints: ORR, DCR, duration/depth of response and OS. DCO: 03 Apr 2023.

Results

Median age (range): 61 (45–84) years; 63% female; 73% Asian, 37% former smoker. Median exposure (range): 38.6 (1.9–44.6) months osi / 15.0 (1.0–64.0) cycles pem; 47% ongoing osi and 17% ongoing pem at DCO; 80% completed 4 cycles carbo/cis-platin. With 3 further years’ exposure, 2 more pts had adverse events (AEs) (n=29 [97%] total), 5 more had serious AEs (n=11 [37%] total), 4 more had Grade ≥3 AEs (n=15 [50%] total) and 1 new AE leading to death (n=2 [7%] total). No new cases of ILD/pneumonitis reported. New Grade ≥3 AEs included COVID-19/pneumonia (n=1 each). New AEs leading to discontinuation: 4 pem (n=10 [33%] total); none osi. No new safety signals were observed. Clinical benefit was observed (Table).

Conclusions

Osi + platinum-pem was well tolerated and clinical benefit continued with 3 further years’ exposure. Data support long-term tolerability of 1L osi + platinum-pem for EGFRm advanced NSCLC. Table: 568P

CI, confidence interval; NC, not calculable; NR, not reached

Clinical trial identification

NCT04035486.

Editorial acknowledgement

The authors would like to acknowledge Gemma White, MSc, of Ashfield MedComms, an Inizio Company, for medical writing support in accordance with Good Publications Practice (GPP) guidelines (https://www.ismpp.org/gpp-2022).

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

D. Planchard: Financial Interests, Personal, Advisory Board: AstraZeneca, AbbVie, Bristol Myers Squibb, Celgene, Daiichi Sankyo, Merck, Novartis, Janssen, Pfizer, Roche, Pierre-fabre, Takeda, ArriVent, Mirati, Seagen; Non-Financial Interests, Institutional, Coordinating PI: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmune, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo, AbbVie, Janssen, Pierre Fabre, Takeda, ArriVent, Mirati, Seagen; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Janssen, Pfizer, Roche, Pierre Fabre, Takeda, ArriVent, Mirati, Seagen. S. Kim: Non-Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Boehringer Ingelheim, Janssen, Norvasc, Takeda, Terrapex, Yuhan; Non-Financial Interests, Personal, Funding: Yuhan; Non-Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim. T.M. Kim: Non-Financial Interests, Personal, Advisory Board: Boryung, Janssen, Novartis, Takeda, Regeneron; Financial Interests, Personal, Advisory Role: AstraZeneca, Boryung, Hanmi, IMBDx, Janssen, Novartis, Takeda, Sanofi, Regeneron, Roche/Genentech, Samsung Bioepis; Non-Financial Interests, Personal, Coordinating PI: Regeneron; Financial Interests, Institutional, Local PI: ABBVIE, AstraZeneca, Bayer, Black Diamond Therapeutics, Blueprint Medicines, Boryung, Bristol Myers Squibb, Celgene, F. Hoffmann-La Roche Ltd/Genentech, Inc, Hanmi, Janssen, Novartis, Regeneron, Sanofi, Takeda, and Yuhan. N. Yanagitani: Non-Financial Interests, Personal, Advisory Board: Pfizer Inc.; Non-Financial Interests, Personal, Speaker, Consultant, Advisor, Consultant: Chugai; Financial Interests, Personal, Speaker, Consultant, Advisor, Lecture Fees: Taiho, MSD, Ono, Bristol Myers Squibb, Novartis, Pfizer Inc., Chugai co., Eli Lilly and Company, Boehringer Ingelheim, Bayer AG. H. Kagamu: Financial Interests, Personal, Research Funding, Collaborative Research Fund: Boehringer Ingelheim Inc., Chugai pharm. Inc., Ono pharm. Inc.; Financial Interests, Personal, Speaker, Consultant, Advisor, Honoraria: AstraZeneca, Bristol Myers Squibb, Ono pharm., Chugai pharm. P. Feng: Non-Financial Interests, Personal, Invited Speaker: Roche, MSD, Ono, AZ; Financial Interests, Personal, Speaker, Consultant, Advisor: PharmaEssentia. B. Hughes: Financial Interests, Personal, Advisory Board: MSD, BMS, AstraZeneca, Roche, Pfizer, Takeda, Sanofi, Eisai; Financial Interests, Personal, Research Funding: Amgen. J.C. Yang: Financial Interests, Institutional, Advisory Board, My institute received fee for my role as advisory board: AstraZeneca, Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Merck KGaA, Merck Sharp & Dohme, Novartis, Pfizer, Roache/Genentech, Takeda, Yuhan Pharmaceuticals, Janssen, Puma Technology, Gilead, GSK, Dizal Pharmaceutica; Financial Interests, Personal, Coordinating PI: AstraZeneca, MSD, Dizal Pharmaceutical; Non-Financial Interests, Personal, Member: ASCO, ESMO, IASLC; Financial Interests, Personal, Research Funding: AstraZeneca, Roche; Financial Interests, Personal, Steering Committee Member: AstraZeneca, Daiichi Sankyo, Eli Lilly, Merck Sharp & Dohme, Takeda, Yuhan Pharmaceuticals, Janssen, Dizal Pharmaceutical. C.K. Lee: Financial Interests, Personal, Advisory Board: AstraZeneca, Amgen, Takeda, Pfizer, Novartis, GSK, Merck KGA, Roche, Janssen, and MSD; Financial Interests, Personal, Research Grant: AstraZeneca, Amgen, Roche, Merck KGA. P. Mitchell: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, BMS, Roche, MSD, Novartis, Pfizer ; Financial Interests, Personal, Advisory Role: Grey Wolf; Financial Interests, Personal, Coordinating PI: AstraZeneca, Amgen. Y. Tambo: Financial Interests, Personal, Speaker, Consultant, Advisor: Chugai, AstraZeneca, Taiho, MSD, Pfizer, Kyowa Kirin. E. Armenteros Monterroso: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. A. Todd: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. A. Sahasrabudhe: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. P.A. Jänne: Financial Interests, Personal, Advisory Board, Consulting fees for advice on drug development: 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, Dr. Jänne is a co-inventor on a DFCI owned patent on EGFR mutations licensed to Lab Corp: Lab Corp; Financial Interests, Personal, Research Grant: AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Takeda Oncology, PUMA, Astellas Pharmaceuticals, Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Post marketing royalties from DFCI owned intellectual property on EGFR mutations licensed to Lab Corp: Lab Corp. K. Kobayashi: Financial Interests, Personal, Financially compensated role, Board Chairman: NPO North East Japan Study Group; Financial Interests, Personal, Speaker’s Bureau, Speaker Fees: AstraZeneca, Takeda Pharmaceutical Co., Daiichi Sanko Pharmaceutical Co., Boehringer Ingelheim. All other authors have declared no conflicts of interest.