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
357P - Application of multi-modal approach to palliation in end of life head and neck cancer pain
Presenter: Srujana Joga
Session: Poster display session
Resources:
Abstract
358P - Evaluation of continuous low dose versus standard dose capecitabine monotherapy as second/third-line chemotherapy for metastatic malignancies
Presenter: Swaroop Revannasiddaiah
Session: Poster display session
Resources:
Abstract
359P - Factors associated with economic burden among cancer patients with minor children: A cross-sectional web-based survey of an online cancer community
Presenter: Midori Yuki
Session: Poster display session
Resources:
Abstract
360P - Factors influencing treatment decisions among breast cancer patients in the Philippine general hospital cancer institute: Medical oncology outpatient clinic
Presenter: Bobby De Guzman
Session: Poster display session
Resources:
Abstract
361P - The role of volunteers in quality palliative care delivery
Presenter: NABANITA MANDAL
Session: Poster display session
Resources:
Abstract
362P - Survey to assess the efficacy of continuity of care delivered through an out of hours telephonic consultation liaison
Presenter: Rahul D. Arora
Session: Poster display session
Resources:
Abstract
366P - Activity of larotrectinib in TRK fusion cancer patients with primary central nervous system tumours
Presenter: David Ziegler
Session: Poster display session
Resources:
Abstract
367P - Molecular characteristics and efficacy of crizotinib among different subsets of MET Amplification detected by next-generation sequencing in lung cancer
Presenter: Jing Li
Session: Poster display session
Resources:
Abstract
368P - Genomic analysis of malaysian breast cancers unravel molecular differences from Caucasian breast cancers
Presenter: Soo-Hwang Teo
Session: Poster display session
Resources:
Abstract
369P - Institutional-based prospective molecular profiling of advanced solid tumours in Hong Kong: A report of 253 cases
Presenter: Herbert Loong
Session: Poster display session
Resources:
Abstract