Abstract CT017: FLAURA2: exploratory analysis of baseline (BL) and on-treatment plasma EGFRm dynamics in patients (pts) with EGFRm advanced NSCLC treated with first-line (1L) osimertinib (osi) ± platinum-pemetrexed
Authors: Pasi A. Jänne, Kunihiko Kobayashi, Jacqulyne Robichaux, Chee Khoon Lee, Shunichi Sugawara, Tsung-Ying Yang, Tae Min Kim, Noriko Yanagitani, Sang-We Kim, Aleksandra Markovets, Preetida Bhetariya, Lynne Poole, Dana Ghiorghiu, Ryan Hartmaier, James Chih-Hsin Yang, David Planchard
Journal: Cancer Research (2024)

Abstract Background In FLAURA2, 1L osi with addition of platinum-pemetrexed chemotherapy (osi + CTx) significantly improved PFS vs osi alone in pts with EGFRm advanced NSCLC. Prior FLAURA analyses showed detected BL plasma EGFRm to be prognostic and early clearance of plasma EGFRm correlated with improved outcomes. We explored correlation of BL plasma EGFRm detection, and its clearance, with PFS in FLAURA2 to determine its potential to identify pts who derive particular benefit from osi + CTx. Methods Treatment-naïve pts with EGFRm (Ex19del or L858R) advanced NSCLC were randomized to osi + CTx (osi 80 mg once daily [QD] + pemetrexed 500 mg/m2 + cisplatin 75 mg/m2 or carboplatin AUC5 every 3 wks [Q3W] for 4 cycles, followed by osi 80 mg QD + pemetrexed 500 mg/m2 Q3W) or osi alone (80 mg QD). BL and wk 3/6 plasma EGFRm were analyzed by ddPCR (Biodesix). Clearance was defined as undetected EGFRm circulating tumor DNA at wk 3/6, where it was detected at BL. Median PFS (mPFS) was investigator-assessed per RECIST 1.1. Results In total, 421/557 pts had an evaluable BL plasma ddPCR result, of who 308 had detected BL plasma EGFRm. Of pts randomized to osi alone, pts with non-detected BL plasma EGFRm had longer mPFS* vs those with detected BL plasma EGFRm. Of pts with evaluable BL and wk 3/6 plasma ddPCR results, plasma EGFRm was detected at wk 3/6 in 19/12% of osi + CTx-treated pts, and 29/11% of osi-treated pts, respectively (Table). Conclusion In this exploratory analysis, detected BL plasma EGFRm was prognostic and appeared predictive of clinical benefit with osi + CTx vs osi alone. Detection of BL plasma EGFRm may identify a subgroup of pts deriving most benefit from the addition of CTx to osi. Although within each treatment arm plasma EGFRm wk3 clearance correlated with improved PFS, the relative benefit of osi + CTx vs osi alone was similar, suggestive that on-treatment EGFRm clearance is only prognostic in this setting. Osimertinib + CTx (evaluable BL ddPCR, n = 212) Osimertinib (evaluable BL ddPCR, n = 209) Osimertinib + CTx vs osimertinib n mPFS (mo) n mPFS (mo) HR (95% CI) Baseline plasma EGFRm Detected 147 24.8 161 13.9* 0.60 (0.45, 0.80) Not detected 65 33.3 48 30.3* 0.93 (0.51, 1.72) EGFRm clearance/non-clearance at 3 weeks Clearance 88 27.6 100 15.2 0.51 (0.35, 0.75) No clearance 21 19.6 40 11.1 0.62 (0.33, 1.14) *Not detected vs detected in the osimertinib arm: mPFS HR 0.51 (95% CI 0.35, 0.76). BL, baseline; CI, confidence interval; CTx, chemotherapy; ddPCR, droplet digital PCR; EGFRm, epidermal growth factor receptor mutation-positive; HR, hazard ratio; mo, months; mPFS, median progression-free survival Citation Format: Pasi A. Jänne, Kunihiko Kobayashi, Jacqulyne Robichaux, Chee Khoon Lee, Shunichi Sugawara, Tsung-Ying Yang, Tae Min Kim, Noriko Yanagitani, Sang-We Kim, Aleksandra Markovets, Preetida Bhetariya, Lynne Poole, Dana Ghiorghiu, Ryan Hartmaier, James Chih-Hsin Yang, David Planchard. FLAURA2: exploratory analysis of baseline (BL) and on-treatment plasma EGFRm dynamics in patients (pts) with EGFRm advanced NSCLC treated with first-line (1L) osimertinib (osi) ± platinum-pemetrexed [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT017.