366MO - Osimertinib plus platinum/pemetrexed in newly diagnosed EGFR mutation (EGFRm)-positive advanced NSCLC: Safety run-in results from the FLAURA2 study

Background

Osimertinib, a 3rd-generation, CNS-active, oral EGFR-TKI, showed superior efficacy vs comparator EGFR-TKIs (erlotinib/gefitinib) in treatment-naïve EGFRm advanced NSCLC (median OS 38.6 vs 31.8 months; median PFS 18.9 vs 10.2 months). Gefitinib plus carboplatin/pemetrexed chemotherapy has shown improved ORR and PFS vs gefitinib alone. Combining osimertinib with platinum/pemetrexed may further improve patient outcomes.

Methods

The safety run-in to allow the opening of the phase III global FLAURA2 (NCT04035486) study was designed to assess safety and tolerability of osimertinib with platinum/pemetrexed chemotherapy. Thirty adults with confirmed EGFRm (ex19del/L858R) locally advanced/metastatic NSCLC, WHO PS 0/1, with no prior therapy for advanced disease, received osimertinib 80 mg QD, and either cisplatin 75 mg/m² (n=15) or carboplatin AUC5 (n=15), plus pemetrexed 500 mg/m² every 3 weeks (Q3W) for 4 cycles, then osimertinib 80 mg QD with pemetrexed 500 mg/m² maintenance Q3W until discontinuation criteria were met (data cut-off [DCO] Feb 2020).

Results

Median age was 61 years (range 45–84), 63% female, 73% Asian, 37% smoker, 67% ex19del/33% L858R. At DCO, 23 (77%) pts had completed 4 cycles of carboplatin/cisplatin chemotherapy. 27 (90%) pts had adverse events (AEs; Table). Two (7%) pts discontinued all study treatments due to AEs, including 1 ILD (CTCAE grade 2) and 1 fatal AE (haemoptysis) attributed to NSCLC, unrelated to treatment. Grade 3 / 4 CTCAE haematological toxicities were reported by 7 / 2 (23 / 7%) pts; the majority recovered by DCO. Table: 366MO

^∗1 pt also discontinued all study treatment due to fatal AE.^†1 pt switched from cisplatin to carboplatin after 1 cycle; pt completed 4 cycles of platinum chemotherapy.

Conclusions

Osimertinib plus platinum/pemetrexed chemotherapy was generally well tolerated; no new safety signals were identified. No clear differences were observed between chemotherapy regimens. These results support further assessment of this combination in the FLAURA2 randomised study period (planned enrolment: 556; primary endpoint: PFS).

Clinical trial identification

NCT04035486.

Editorial acknowledgement

Alexandra Webster, MSc, from iMed Comms, an Ashfield Company, part of UDG Healthcare plc, who provided medical writing support funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

D. Planchard: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Boehringer Ingelheim; Celgene; Eli Lilly; Merck; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Pfizer; prIME Oncology; Honoraria (self), Advisory/Consultancy: Peer CME; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Daiichi Sankyo; Samsung. T.M. Kim: Honoraria (institution), Advisory/Consultancy: AstraZeneca; Boryung; Novartis; Regeneron; Roche/Genentech; Sanofi; Takeda; Voronoi; Research grant/Funding (self), outside this work: AstraZeneca-KHIDI. C.K. Lee: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: Takeda. N. Yanagitani: Advisory/Consultancy: Chugai Pharmaceutical Co., Ltd. S. Powar: Full/Part-time employment: AstraZeneca. X. Huang: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. P. Howarth: Full/Part-time employment: AstraZeneca. P. Jänne: Advisory/Consultancy, Research grant/Funding (self): AstraZeneca, Boehringer Ingelheim; Licensing/Royalties: LabCorp; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy: Acea Biosciences; Advisory/Consultancy: Ignyta; Shareholder/Stockholder/Stock options: Loxo Oncology, Gatekeeper Pharmaceuticals; Advisory/Consultancy, Research grant/Funding (self): Eli Lilly pharmaceuticals; Advisory/Consultancy: Araxes pharmaceuticals; Advisory/Consultancy: SFJ Pharmarceuticals; Advisory/Consultancy: Voronoi; Advisory/Consultancy, Research grant/Funding (self): Daiichi Sankyo; Advisory/Consultancy: Biocartis; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Takeda Oncology; Advisory/Consultancy: Mirati Therapeutics; Research grant/Funding (self): Astellas Pharmaceuticals; Research grant/Funding (self): Puma; Research grant/Funding (self): Revolution Medicines; Research grant/Funding (self): Takeda Oncology. K. Kobayashi: Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Bristol-Myers Squibb Japan; Speaker Bureau/Expert testimony: Ono Pharmaceutical; Speaker Bureau/Expert testimony: Boehringer Ingelheim; Speaker Bureau/Expert testimony: Taiho Pharmaceutical Company. All other authors have declared no conflicts of interest.