Abstract 483P
Background
Treatment with an EGFR TKI is the standard of care for patients (pts) with EGFR mutation-positive (EGFRm+) NSCLC, based on findings from randomized controlled trials, but acquired resistance is inevitable. A phase IIIb study (NCT01853826) was conducted to assess outcomes with afatinib in a broad EGFRm+ NSCLC patient population, similar to real-world practice. Here we report results from a sub-study of the trial, to assess the relationship between afatinib efficacy and the presence of biomarkers associated with resistance to EGFR TKIs.
Methods
EGFR TKI-naïve pts with locally advanced/metastatic EGFRm+ NSCLC and ECOG PS 0–2 received afatinib starting at 40 mg/day. Tumor biopsies were performed prior to study entry; baseline T790M status (presence vs absence), and total BIM, BIMEL and mTOR mRNA expression (high vs low, according to median values) were analyzed for patients who consented to sub-study participation. Exploratory efficacy analyses were conducted. Time to symptomatic progression (TTSP) and progression-free survival (PFS) were calculated using the Kaplan–Meier method.
Results
A total of 113 pts were included in this sub-study (data cut-off 21 June 2018). Baseline characteristics, n (%): white race, 112 (99); female, 70 (62); 1st/2nd/≥3rd-line therapy, 94/16/3 (83/14/3); ECOG PS 0/1, 106 (94); brain metastases, 16 (14); common/uncommon mutations, 105/8 (93/7). Median time on treatment was 581 days. Objective response/disease control rates were 58%/95%. Median (95% CI) TTSP was 20.6 months (18.9–24.9) and PFS was 19.8 months (16.1–23.5). TTSP and PFS by biomarker status at baseline are reported in the table.
Table: 483P
TTSP | PFS | |||
---|---|---|---|---|
Median (95% CI) | HR (95% CI) | Median (95% CI) | HR (95% CI) | |
T790M* | ||||
Present (n = 51) Absent (n = 60) | 19.5 (14.9–25.1) 21.4 (17.7–26.3) | 1.0 (0.67–1.60) | 18.8 (14.1–24.0) 21.4 (15.9–26.1) | 1.1 (0.7–1.7) |
BIM total mRNA expression† | ||||
High (n = 35) Low (n = 35) | 23.7 (14.7–37.1) 25.7 (19.3–35.8) | 1.2 (0.7–2.1) | 21.8 (14.1–28.5) 26.0 (18.9–35.5) | 1.2 (0.7–2.1) |
BIMEL mRNA expression‡ | ||||
High (n = 22) Low (n = 21) | 19.1 (11.9–24.8) 24.9 (14.8–42.2) | 1.3 (0.6–2.7) | 18.8 (11.6–23.5) 25.2 (16.1–38.6) | 1.4 (0.7–2.9) |
mTOR mRNA expression§ | ||||
High (n = 39) Low (n = 37) | 22.3 (14.8–29.5) 26.1 (19.1–35.8) | 1.0 (0.6–1.7) | 21.8 (14.3–29.5) 23.1 (14.5–35.5) | 1.0 (0.6–1.8) |
Non-evaluable or missing: *n=2; †n = 43; ‡n = 36; §n = 37.
Conclusions
In this broad population of EGFR TKI-naïve pts with EGFRm+ NSCLC who were treated with afatinib, biomarker analysis indicated no notable differences in efficacy outcomes by baseline T790M status (presence vs absence), or baseline mRNA expression of BIM, BIMEL or mTOR (high vs low).
Clinical trial identification
NCT01853826.
Editorial acknowledgement
Laura Winton of GeoMed, an Ashfield company, part of UDG Healthcare plc.
Legal entity responsible for the study
Boehringer Ingelheim.
Funding
Boehringer Ingelheim.
Disclosure
M. Hochmair: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Sharp & Dohme, ; Advisory / Consultancy: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy: Takeda; Speaker Bureau / Expert testimony: Pfizer. R. Ramlau: Advisory / Consultancy: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer Ingelheim; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca. J. Skrickova: Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Roche. P. Bidoli: Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: BMS ; Advisory / Consultancy: Boehringer Ingelheim. L. Clementi: Full / Part-time employment: Boehringer Ingelheim. A. Cseh: Full / Part-time employment: Boehringer Ingelheim. F. De Marinis: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Advisory / Consultancy: Takeda; Research grant / Funding (institution): Boehringer Ingelheim. All other authors have declared no conflicts of interest.
Resources from the same session
511P - Phase II trial of carboplatin, nab-paclitaxel and bevacizumab for advanced non-squamous non-small cell lung cancer (CARNAVAL study; TORG1424/OLCSG1402)
Presenter: Toshio Kubo
Session: Poster display session
Resources:
Abstract
485P - A real-world experience of first-line afatinib in Korean patients with EGFR-mutant non-small cell lung cancer
Presenter: Seong Hoon Yoon
Session: Poster display session
Resources:
Abstract
522P - Weekly nab-PTX and weekly PTX for relapsed small cell lung cancer
Presenter: Hajime Oi
Session: Poster display session
Resources:
Abstract
512P - A phase I and extension study of S-1 and carboplatin for previously untreated patients aged 75 years or more with advanced non-small cell lung cancer
Presenter: Hisao Imai
Session: Poster display session
Resources:
Abstract
497P - Real-word efficacy of osimertinib in patients with metastatic EGFRm NSCLC: An interim analysis from a multi-center study in China
Presenter: Xiangyun Ye
Session: Poster display session
Resources:
Abstract
507P - Immune checkpoint inhibitors for patients acquired resistance to tyrosine kinase inhibitors with EGFR mutated non-small cell lung cancer: A multicenter retrospective study
Presenter: Takeshi Uenami
Session: Poster display session
Resources:
Abstract
516P - Clinical outcomes in elderly patients with advanced non-small cell lung cancer: A prospective multicenter study of the National Hospital Organization in Japan
Presenter: Masahiro Shimada
Session: Poster display session
Resources:
Abstract
486P - Phase II study of low-dose afatinib maintenance treatment for patients with EGFR-mutated non-small cell lung cancer (NJLCG1601)
Presenter: Mami Morita
Session: Poster display session
Resources:
Abstract
515P - Polypharmacy as a prognostic factor in elderly patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors
Presenter: Taiki Hakozaki
Session: Poster display session
Resources:
Abstract
518P - Real world prospective clinical impact of finding actionable genomic alterations by plasma cell-free DNA next generation sequencing in advanced non-small cell lung cancer
Presenter: Beung chul Ahn
Session: Poster display session
Resources:
Abstract