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Poster Display session (Friday) (ID 65)
- Event: ELCC 2018
- Type: Poster Display session
- Presentations: 1
- Coordinates: 4/13/2018, 12:30 - 13:00, Hall 1
149P - Real-world outcomes with first-line afatinib in EGFR mutant NSCLC adenocarcinoma: A single centre experience exploring effects of dose-reduction (ID 274)
12:30 - 13:00 | Author(s): R. Kumar
Tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR-TKI) are indicated for first-line treatment of EGFR+ advanced/metastatic NSCLC, having demonstrated superior progression free survival (PFS) and tolerability over chemotherapy in this setting. Afatinib is the only EGFR-TKI to have also shown superior overall survival (OS) over chemotherapy in patients with EGFR 19del mutations, albeit with higher toxicity: 53% and 28% dose reductions (DR) were reported in LUX-LUNG 3 (LL3) and LUX-LUNG 6 (LL6) trials, respectively. Effects of toxicities on treatment delivery and efficacy in the real-world UK population are unknown.
Retrospective review of outcomes in patients with EGFR+ treatment naïve advanced/metastatic NSCLC treated with afatinib at a single UK centre. Primary endpoint: PFS. Key secondary endpoints: rate of DR; relative dose intensity; toxicities; objective response rate (ORR); PFS according to DR vs no DR; OS overall, by DR vs. no DR, and by mutation type. Survival analyses were performed using Kaplan-Meier methods and compared using the log-rank test.Table:Patient demographics and baseline characteristics (n = 44)
Patient demographics and baseline characteristic (n = 44) No. (%) Age (median, range) 63.5 (31–85) Gender M 19 (43.2) F 25 (56.8) Ethnicity Caucasian 29 (65.9) Asian 11 (25) Other 4 (9.1) Stage at diagnosis 2 (4.5) IIIA 3 (6.8) IIIB 1 (2.3) IV 38 (86.4) ECOG performance status at start of afatinib 0 9 (20.5) 1 29 (65.9) 2 6 (13.6) Comorbidities None 18 (40.9) Mild 23 (52.3) Moderate 3 (6.8) EGFR mutation Exon 19 del 29 (65.9) L858R 11 (25.0) G719X 2 (4.5) S768I 1 (2.3) Exon 20 ins 1 (2.3) Starting dose of afatinib 40 mg 40 (90.9) 30 mg 4 (9.1)
44 patients received first-line afatinib (30–40 mg) between September 2012 and July 2017. Patient characteristics are shown in the Table. 70% patients had at least one DR, 29% during the first cycle. Relative dose intensity was 77.1%. The most common toxicity was diarrhoea (32%), followed by skin rash (22%) and paronychia (18%). Out of 42 evaluable patients, 74% achieved partial response (56% and 67% in LL3 and LL6, respectively). Disease control rate was 93% (LL3: 90%, LL6: 93%). After median follow-up of 26 months, 27/42 patients had disease progression or death on afatinib, 10 patients remained on afatinib and 5 switched to other EGFR-TKI due to intolerable toxicities. mPFS was 12.3mo (LL3: 11.1mo, LL6: 11mo). mPFS in patients with a DR was 22.7mo vs. 12.3mo if no DR (HR 0.69, p = 0.38). Median OS was 31.4mo (LL3: 28.2mo, LL6: 23.1mo). There was no significant difference in mOS for patients with DR vs. no DR (31.4 vs 24.4mo, HR 1.51, p = 0.46). There was a trend towards greater OS for patients with EGFR del19, but not statistically significant (p = 0.23). EGFR T790M testing was available for 19 patients after progression on afatinib, with 6 positive for T790M, all of whom went on to a third-generation EGFR-TKI.
Dose reductions on afatinib are required in a majority of real-world patients, with no significant detrimental impact on efficacy and long-term survival outcomes which, in our cohort, were consistent with trial data.
Clinical trial identification:
Legal entity responsible for the study:
Royal Marsden Hospital
Has not received any funding
M. O'Brien: Advisory work for BI. J. Bhosle: Honoraria from Boehringer Ingelheim. S. Popat: Consulting/advisory for Boehringer Ingelheim. All other authors have declared no conflicts of interest.
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