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
74TiP - Phase I study of BI 836880, a VEGF/Ang2-blocking nanobody®, as monotherapy and in combination with BI 754091, an anti-PD-1 antibody, in Japanese patients (pts) with advanced solid tumours
Presenter: Kentaro Yamazaki
Session: Poster display session
Resources:
Abstract
75P - A parallel deep learning network framework for whole-body bone scan image analysis
Presenter: Xiaorong Pu
Session: Poster display session
Resources:
Abstract
76P - Perception and satisfaction of cancer patients in clinical trials
Presenter: Jukyung Jeon
Session: Poster display session
Resources:
Abstract
77P - A prognostic nomogram for the prediction of neuroblastoma
Presenter: Jian-Guo Zhou
Session: Poster display session
Resources:
Abstract
80P - The clinical usefulness of a new fat-dissociation method to detect lymph nodes from surgically resected specimen in colorectal cancer: Prospective randomized study
Presenter: Shiki Fujino
Session: Poster display session
Resources:
Abstract
81P - Concurrent or consolidation chemotherapy during radiation as neoadjuvant treatment for locally advanced rectal cancer: A propensity score analysis from two prospective study
Presenter: JianWei Zhang
Session: Poster display session
Resources:
Abstract
82P - Body mass index, tumour location, and colorectal cancer survival
Presenter: Dake Chu
Session: Poster display session
Resources:
Abstract
83P - Helicobacter bilis may play a role in the carcinogenesis of colitis associated colon cancer correlating to increased number of CD4+CD45RB+ T cells
Presenter: Xiangsheng Fu
Session: Poster display session
Resources:
Abstract
84P - Comprehensive evaluation of relapse risk (CERR) score for colorectal liver metastases development and validation
Presenter: Jianmin Xu
Session: Poster display session
Resources:
Abstract
85P - Which is the best partner for capecitabine-based neoadjuvant chemoradiotherapy in locally advanced rectal cancer? A retrospective analysis of a comprehensive cancer center
Presenter: Jingwen Wang
Session: Poster display session
Resources:
Abstract