First-line Afatinib (A) vs Gefitinib (G) for Patients (pts) with EGFR Mutation Positive (EGFRm+) NSCLC (LUX-Lung 7): Patient-reported Outcomes (PROs) and Impact of Dose Modifications on Efficacy and Adverse Events (AEs)
Invited conference paper presented and published in conference proceedings


摘要Background: The phase IIb LUX-Lung 7 (LL7) trial compared the 2nd-generation ErbB family blocker, A 40 mg/day, and the 1st-generation reversible EGFR TKI, G 250 mg/day in pts with treatment (tx) naïve EGFRm+ NSCLC. The co-primary endpoints, PFS and TTF were significantly better with A vs G, as was ORR. To explore pt experience of tx we report PROs (secondary endpoint) and post-hoc analysis of the impact of dose adjustment of A on PFS and AEs. Methods: PROs were assessed using EQ-5D utility and EQ-VAS scores. To optimize individual tolerability, the dose of A could be reduced by 10 mg decrements to a minimum of 20 mg in the event of grade ≥ 3 (or selected grade 2) drug-related (DR) AEs. PFS was compared between pts who had a dose reduction within 6 mos and those who received ≥ 40mg for the first 6 mos. Incidence/severity of common AEs before/after dose reduction from 40 mg was assessed. Results: There was no significant/clinically meaningful difference in mean EQ-5D (baseline to post-baseline, A: 0.72 to 0.77; G: 0.73 to 0.80; p = 0.142) or EQ-VAS (A: 69.7 to 74.5; G: 71.2 to 76.0; p = 0.20) with A and G. Of 160 pts treated with A (40 mg), 63 (39%) had a dose reduction to 30 mg; 21 (13%) had a further dose reduction to 20 mg. Dose reductions were more frequent in non-Asians than Asians (64 vs 36%). There was no significant difference in PFS in pts who received < 40 mg or ≥40 mg (median: 12.8 vs 11.0 mos; HR [95% CI]: 1.3 [0.9–2.0]; p = 0.14). Dose reduction of A reduced the incidence/severity of DR AEs (Table), and did not diminish its effects on PROs (EQ-5D, < 40 mg: 0.69 to 0.74, ≥ 40 mg: 0.73 to 0.77; EQ-VAS, < 40 mg: 72.4 to 70.5, ≥40 mg: 68.6 to 75.4). Conclusions: Improvements in PROs were similar in pts treated with A or G. As with LL3/LL6 dose adjustment of A in LL7 reduced the frequency/intensity of DR AEs without compromising efficacy. This enables pts to remain on effective tx without affecting PROs. Clinical trial information: NCT01466660
著者HIRSH Vera, YANG James Chih Hsin, TAN Eng Huat, O BYRNE Ken, ZHANG Li, BOYER Michael J, MOK Shu Kam Tony, LEE Ki Hyeong, LU Shun, SHI Yuankai, KIM Sang We, LASKIN Janessa J, KIM Dong Wan, ARVIS Catherine Dubos, KOLBECK Karl, SCHULER Martin H, MASSEY Dan, MAERTEN Angela, PAZ ARES Luis, PARK Keunchil
會議名稱ASCO 2016 Annual Meeting
會議地點Chicago, Illinois
會議論文集題名Journal of Clinical Oncology
詳細描述organized by American Society of Clinical Oncology,
期次Suppl. 15
出版地United States of America
頁次9046 - 9046

上次更新時間 2018-20-01 於 19:40