Abstract 1858
Background
The second-generation afatinib has shown longer Progression-Free Survival (PFS) than gefitinib in the first line treatment of advanced EGFR mutated lung cancer, and has excellent penetration into the central nervous system. It is licensed at a starting dose of 40mg/day, but in real-life practice dose reductions due to toxicity are common. As for other targeted agents, it is questionable if dose selection should be based on biological active dose instead of maximum tolerable dose. Here we aimed to identify the frequency of afatinib dose reductions and analyse their impact in survival outcomes in the UK real-life population.
Methods
Patients with EGFR-mutated lung cancer treated with afatinib between April 2014 and December 2017 in four UK centres were retrospectively identified. The frequency of dose reductions and response rates was quantified. Dose Intensity (DI; average daily dose over the total treatment period) was calculated and patients were grouped into DI > 30mg/day and DI ≤ 30mg/day; PFS and Overall Survival (OS) curves were plotted.
Results
98 patients were identified. The median treatment duration was 8.5 months (range 01.-42.7), and mean DI 30.6mg/day. 85 patients started at 40mg/day and 13 at 30mg/day. They required dose reductions in 65% (n = 55) and 46% (n = 6), respectively. The starting dose did not influence response rates. 50 patients (51%) received a DI ≤ 30 and 48 patients (49%) received a DI > 30. A lower DI did not significantly influence PFS (HR 0.65(0.37-1.14); p = 0.127) or OS (HR 0.58(0.28-1.20); p = 0.14), but showed a trend to better outcomes. Patients with brain metastasis (n = 11(22%) DI ≤ 30 and n = 14(29%) DI > 30) had similar clinical outcomes regardless of DI, and patients that required a reduction to the lowest dose of 20mg/day (n = 28) achieved similar PFS (HR 0.58(0.3-1.14); p = 0.113) and OS (HR 0.41 (0.16-1.08); p = 0.062) as the rest (n = 70).
Conclusions
Our results suggest equal clinical efficacy in patients treated with a lower DI of afatinib, and a reduced need for dose reductions in patients starting at 30mg/day. Prospective tolerability and efficacy of afatinib starting at 30mg/day will be quantified in a phase II UK study.
Clinical trial identification
Legal entity responsible for the study
The Clatterbridge Cancer Centre NHS Trust.
Funding
Has not received any funding.
Editorial Acknowledgement
Disclosure
R. Shah: Advisory board: Boehringer Ingelheim. Q. Ghafoor: Consultancy: Roche, AstraZeneca, Boehringer Ingelheim, Pfizer. S. Popat: Honoraria, consulting and research funding: Boehringer Ingelheim. P.E. Postmus: Paid member of advisory board: Boehringer Ingelheim. All other authors have declared no conflicts of interest.