Abstract 503P
Background
In the registrational trials, afatinib (afa) was active against NSCLC tumors harboring common and uncommon EGFR mutations, including G719X, L861Q and S768I,1 and is approved in this setting. Here, we assess 1st-line afa in pts with uncommon EGFR mutations treated in a ‘real-world’ setting in the largest analysis of its kind to date.
Methods
Retrospective pooled analysis of three ‘real-world’ studies: an expanded-access program in Korea (1200.193); an Asian phase IIIB trial (1200.66); a global phase IIIB trial (mainly Europe; 1200.55). Pts had EGFR mutation-positive (EGFRm+) NSCLC, were EGFR TKI-naïve, and received afa 40 mg/day. Dose reduction was permitted (minimum 20 mg/day). Endpoints included time to symptomatic progression (TTSP), investigator-assessed PFS and ORR.
Results
Overall, 1108 pts were treated with afa: median age, 61 yrs; female, 58%; ECOG PS of 0/1/2, 26%/70%/4%; asymptomatic brain metastases, 19%; 1st-line afatinib, 69%. 198 (18%) had tumors harboring at least one uncommon mutation (exon 20 insertions [Ins20]: n = 70; T790M: n = 20; G719X: n = 41; L861Q: n = 47; S768I: n = 20; other: n = 25. Of note, 35% of pts had Ins20 mutations, a heterogeneous group generally resistant to EGFR TKIs). Median TTSP, PFS and ORR were 8.3 mos (95% CI 7.2–11.0), 7.4 mos (95% CI 6.0–9.0) and 37% respectively. Median duration of response was 10.2 mos (95% CI 8.4–12.9). In those pts with uncommon mutations and brain metastases, median TTSP and PFS were 7.6 mos (95% CI 4.6–10.1) and 7.4 mos (95% CI 4.6–9.1). Clinical activity in pts with uncommon mutations was greatest against tumors harboring G719X, L861Q or S768I. Some pts with Ins20 or T790M mutations appeared to benefit from treatment. Survival data in specific mutation subgroups will be presented.
Conclusions
In this ‘real-world’ analysis, nearly 20% of pts with EGFRm+ NSCLC harbored uncommon EGFR mutations. Afa was active in a broad range of these pts, including some with Ins20 mutations. 1. Yang, JC. et al. Lancet Oncol 2015;16:830–8.
Table: 503P
EGFR mutation type | ||||||
---|---|---|---|---|---|---|
Common | Uncommon | |||||
Del19 | L858R | T790M | Ins20 | T790M + Ins 20 | G719X, L861Q, S768I and Other | |
n | 531 | 378 | 15 | 65 | 5 | 113 |
Median TTSP, mos (95% CI) | 17.2 (15.5, 19.3) | 14.5 (13.1, 16.5) | 8.2 (2.7, 13.4) | 5.9 (3.8, 8.2) | 1.5 (0.1, 13.0) | 11.0 (9.0, 16.4) |
Median PFS, mos (95% CI) | 14.5 (13.8, 15.9) | 12.6 (11.1, 13.8) | 7.1 (2.0, 9.0) | 5.6 (3.9, 7.4) | 1.5 (0.1, 9.1) | 9.2 (7.3, 12.1) |
ORR, % | 64 | 52 | 20 | 23 | 20 | 49 |
Median DOR, mos (95% CI) | 14.1 (12.6, 16.2) | 12.5 (11.1, 14.9) | 12.5 (1.1, 12.5) | 10.1 (3.7, 21.2) | 8.3 (NE, NE) | 10.2 (8.3, 15.5) |
Clinical trial identification
NCT01931306; NCT01953913; NCT01853826.
Editorial acknowledgement
Lynn Pritchard of GeoMed, an Ashfield company, part of UDG Healthcare plc.
Legal entity responsible for the study
Boehringer Ingelheim.
Funding
Boehringer Ingelheim.
Disclosure
F. De Marinis: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Advisory / Consultancy: Takeda; Research grant / Funding (institution): Boehringer Ingelheim. V. Lee: Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self): Eli Lilly; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Merck Sharp & Dohme. L. Clementi: Full / Part-time employment: Boehringer Ingelheim. W. Tang: Full / Part-time employment: Boehringer Ingelheim. D.C-L. Huang: Full / Part-time employment: Boehringer Ingelheim. A. Cseh: Full / Part-time employment: Boehringer Ingelheim. K. Park: Advisory / Consultancy: AMGEN; Advisory / Consultancy: Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): AstraZeneca; Advisory / Consultancy: BluePrint; Advisory / Consultancy: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Hanmi; Advisory / Consultancy: KHK; Advisory / Consultancy: Loxo; Advisory / Consultancy: Merch KGaA; Advisory / Consultancy, Research grant / Funding (self): MSD; Advisory / Consultancy: ONO; Advisory / Consultancy: Roche. C. Zhou: Honoraria (self): BI; Honoraria (self): Roche; Honoraria (self): Sanofi; Honoraria (self): Hengrui; Honoraria (self): Qilu; Honoraria (self): MSD. Y-L. Wu: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self): Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (self): Pfizer; Honoraria (self): Eli Lilly; Honoraria (self): MDS; Honoraria (self): BMS. All other authors have declared no conflicts of interest.
Resources from the same session
248P - Retrospective review of metastatic carcinoma of cervix from a tertiary cancer institute of south India
Presenter: Arkoprovo Halder
Session: Poster display session
Resources:
Abstract
249P - Accuracy of endometrial biopsy by Pipelle: A systematic review and meta-analysis
Presenter: Jinhai Gou
Session: Poster display session
Resources:
Abstract
250P - Non-endometrioid endometrial cancer: Analysis of different adjuvant treatment modalities
Presenter: Gonçalo Nogueira da Costa
Session: Poster display session
Resources:
Abstract
251P - A prognostic index model for predicting long-term recurrence of uterine leiomyoma after initial myomectomy in women aged 18-44 years
Presenter: Xiu Ming
Session: Poster display session
Resources:
Abstract
252P - Uterine sarcomas in Qatar: Clinico-pathological characteristics and treatment outcome
Presenter: Ashraf Fadlelseid
Session: Poster display session
Resources:
Abstract
253P - Anti-PD-1-induced reinvigoration of tumour-infiltrating CD8+ T cells in epithelial ovarian cancer patients is correlated with T cell factor-1
Presenter: Junsik Park
Session: Poster display session
Resources:
Abstract
254P - Cyclin E1 is a shared biomarker of subsets of high grade serous ovarian cancer (HGSOC) and basal like breast cancer (BLBC)
Presenter: Diar Aziz
Session: Poster display session
Resources:
Abstract
255P - MEX3A is a prognostic biomarker and correlates with RNA splicing and cell proliferation in endometrial cancer by analysis of RNA-seq data
Presenter: Huining Jing
Session: Poster display session
Resources:
Abstract
256P - Lnc-AL445665.1-4 may be involved in the development of multiple uterine leiomyoma through interacting with miR-146b-5p
Presenter: E Yang
Session: Poster display session
Resources:
Abstract
257P - Treatment results of low risk gestational trophoblastic neoplasia (GTN) from a tertiary hospital, Chennai, India
Presenter: Rakesh M. P
Session: Poster display session
Resources:
Abstract