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Michael Schumacher
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P2.14 - Targeted Therapy (ID 183)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.14-58 - A Phase IIIb, Open-Label Study of Afatinib in Caucasian EGFR TKI-Naïve Patients with EGFRm+ NSCLC: An Interim Analysis (ID 1371)
10:15 - 18:15 | Author(s): Michael Schumacher
- Abstract
Background
First-line afatinib demonstrated significantly improved median PFS in patients with EGFR mutation-positive (EGFRm+) NSCLC versus chemotherapy in LUX-Lung 3/6 (HR [95% CI]: 0.58 [0.43–0.78]/0.28 [0.20–0.39]), and versus gefitinib in LUX-Lung 7 (0.73 [0.57–0.95]). Since these trials had strict inclusion criteria, it is important to support these findings with real-world studies of broader patient populations. We report interim results of a Phase IIIb study of afatinib treatment for EGFRm+ NSCLC in a patient population similar to real-world practice.
Method
EGFR TKI-naïve patients with locally advanced/metastatic EGFRm+ NSCLC, and ECOG PS 0–2, received afatinib 40 mg/day. Dose reduction was permitted (minimum 20 mg/day). Primary endpoint: adverse events (AEs; descriptive fashion). Efficacy was also assessed.
Result
At data cut-off (30-April-2018), 479 patients were enrolled and treated (Caucasian/Asian/other: 97%/2%/<1%; ECOG PS 0–1/2: 92%/8%; 1st/2nd/≥3rd-line therapy: 78%/17%/5%; common/uncommon mutations: 87%/13%; brain metastases: 17%). Median time on afatinib: 359 days. Objective response and disease control rates were 46% and 86%, respectively. Other efficacy outcomes are in the Table. The most common grade ≥3 afatinib-related AEs were diarrhoea (16%) and rash (11%). 258 (54%) patients had AEs leading to dose reduction (most frequently diarrhoea [25%]/rash [11%]), and 37 (8%) had TRAEs leading to discontinuation (most frequently diarrhoea [3%]; all others [<1%]). Serious afatinib-related AEs occurred in 39 (8%) patients.
Median TTSP, months
(95% CI)
Median PFS, months
(95% CI)
All pts (n=479)
14.9
(13.8–17.6)
13.4
(11.8–14.5)
Line of therapy
1st (n=374)
15.6
(14.1–18.5)
13.8
(12.6–15.2)
2nd (n=81)
14.7
(11.3–20.6)
13.2
(8.3–17.7)
≥3rd (n=24)
8.1
(3.7–14.4)
6.6
(3.2–12.6)
Baseline brain metastases*
No (n=395)
15.8
(14.1–18.8)
13.9
(12.7–15.5)
Yes (n=83)
13.7
(9.7–17.2)
10.1
(8.2–13.9)
Baseline mutation type*
Common† (n=416)
15.9
(14.5–19.1)
14.1
(13.0–15.7)
Uncommon‡ (n=62)
6.7
(5.4–8.3)
5.9
(4.0–7.4)
Baseline ECOG PS*, including age
0–1 (n=442)
15.8
(14.4–18.8)13.8
(12.8–15.2)<65 years (n=221)
14.7
(12.7–17.6)13.4
(11.6–15.5)≥65 years (n=221)
18.9
(14.7–21.7)14.1
(12.6–16.4)2 (n=36)
8.9
(5.7–13.2)6.2
(2.5–11.6)<65 years (n=16)
6.0
(2.4–13.2)3.2
(1.5–9.1)≥65 years (n=20)
9.9
(7.6–13.9)7.7
(5.7–13.9)*Missing (n=1); †Del 19 and/or L858R with or without uncommon mutation; ‡Includes, n (%, of those with uncommon mutations): ex 20 ins: 37 (60), T790M: 12 (19), G719S/A/C: 12 (19), L861Q: 10 (16), S768I: 9 (15). TTSP, time to symptomatic progression; PFS, progression-free survival
Conclusion
This interim analysis indicated predictable and manageable safety, and encouraging efficacy, with afatinib in a broad patient population. The high proportion of patients with tumours harbouring exon 20 insertions may account for the differences in TTSP/PFS by common/uncommon mutation subgroup. Independent of treatment line, median TTSP/PFS in patients with ECOG PS 0–1 (LUX-Lung trials’ inclusion criteria) was 15.8/13.8 months, and, notably, was 18.9/14.1 months in those also aged ≥65 years. These findings by ECOG PS/age are consistent with those of the LUX-Lung trials.
