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P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Presentations: 1
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
P1.01-98 - A Phase IIIb Trial of Afatinib in EGFRm+ NSCLC: Analyses of Outcomes in Patients with Brain Metastases or Dose Reductions (ID 12906)
16:45 - 18:00 | Author(s): Ching-Liang Ho
We previously reported interim results of a large (n=479) open-label, single-arm Phase IIIb study of afatinib in EGFR TKI-naïve patients with EGFRm+ NSCLC, in a setting similar to ‘real-world’ practice (Wu et al, WCLC, 2017). In this broad population of Asian patients, the tolerability profile of afatinib was predictable and manageable. Adverse events (AEs) were consistent with the LUX-Lung 3, 6 and 7 trials; 3.8% of patients discontinued due to drug-related AEs. Progression-free survival (PFS) and time to symptomatic progression (TTSP) was encouraging, in patients with both common and uncommon EGFR mutations. TTSP data suggested effective treatment beyond progression. Here, we assess the impact of baseline brain metastases and use of dose reductions on efficacy outcomes.a9ded1e5ce5d75814730bb4caaf49419 Method
Patients with locally advanced/metastatic EGFRm+ NSCLC were recruited in China, Hong Kong, India, Singapore and Taiwan. Afatinib 40mg/day was given until disease progression (investigator-assessed) or lack of tolerability. Treatment-related AEs could be managed by protocol-specified tolerability-guided dose adjustment.4c3880bb027f159e801041b1021e88e8 Result
At data cut-off (13 Feb 2017), patient characteristics were as follows: median age, 59.0 years; female, 52.4%; EGFR mutations: Del19+/-L858R+/-uncommon, 86.0%; uncommon only, 14.0%; ECOG PS0, 19.8%; PS1, 78.1%. Prior chemotherapy lines: 0, 59.7%; 1, 30.1%; ≥2, 10.2%.
Overall, dose reductions from 40mg/day to 30mg/day occurred in 119 patients (25%). Incidences of the most frequently reported AEs before and after dose reduction were (any grade): diarrhea, 96/51%; rash/acne, 69/58%; stomatitis, 65/42%; (≥grade 3) diarrhea, 27/4%; rash/acne, 24/11%; stomatitis, 11/5%. A total of 96 patients had a dose reduction during the first six months; median PFS in this subgroup was 14.1 months (95% CI: 10.0–19.3) versus 11.33 (10.7–13.6) months in those who remained on the starting dose (n=383); HR=1.37 (1.01–1.85), p=0.041. Median TTSP was 17.7 (13.5–23.7) and 14.7 (12.7–17.0) months, respectively; HR=1.26 (0.92–1.72), p=0.15.
Among 92 patients (19.2%) with brain metastases at baseline, median PFS was 10.9 (8.3–14.3) months, versus 12.4 (10.8–13.9) months in those without metastases (n=387); HR=1.23 (0.91–1.65), p=0.18. Median TTSP was 14.8 (12.7–20.7) and 15.4 (12.9–18.0) months, respectively; HR=1.0 (0.71–1.40), p=1.0.8eea62084ca7e541d918e823422bd82e Conclusion
These findings demonstrate that tolerability-guided dose adjustment of afatinib is an effective measure to reduce treatment-related AEs, while maintaining therapeutic efficacy. TTSP was similar between patients with and without brain metastasis. This is additional evidence for the efficacy of afatinib in patients with brain metastases.6f8b794f3246b0c1e1780bb4d4d5dc53