Abstract 482P
Background
First-line afatinib significantly improved median progression-free survival (PFS) in pts with EGFRm+ NSCLC vs chemotherapy (CT) in LUX-Lung (LL) 3/6 (HR [95% CI]: 0.58 [0.43, 0.78]/0.28 [0.20, 0.39]), and vs gefitinib in LL7 (0.73 [0.57, 0.95]). We conducted a phase IIIb study of afatinib in a broader patient population, similar to real-world practice, of treatment-naïve or CT pre-treated pts with EGFRm+ NSCLC. Here we present an interim analysis.
Methods
EGFR TKI-naïve pts with locally advanced/metastatic EGFRm+ NSCLC and ECOG PS 0–2 received afatinib 40 mg/day; dose reduction was permitted (min. 20 mg/day). Primary endpoint: adverse events (AEs; descriptive fashion). Efficacy was assessed and post-hoc subgroup analysis conducted.
Results
479 pts were included (data cut-off: 30/04/18): Caucasian/Asian: 97%/2%; female: 66%; 1st/2nd/≥3rd-line therapy: 78%/17%/5%; ECOG PS 0 or 1/2: 92%/8%; brain metastases: 17%; common/uncommon [C/U] mutations: 87%/13%. Median time on afatinib: 359 days. Objective response rate: 46%. Disease control rate: 86%. Median time to symptomatic progression (TTSP) and PFS were 14.9 (95% CI: 13.8, 17.6) and 13.4 (11.8, 14.5); subgroup analysis is in the table. Most common grade ≥3 afatinib-related AEs were diarrhea (16%) and rash (11%). AEs led to dose reduction in 258 (54%) pts (most frequently diarrhea 25%, rash 11%) and to afatinib discontinuation in 105 (22%) pts (malignant neoplasm progression 3%, diarrhea 3% [rash 0.8%]). Afatinib-related serious AEs occurred in 39 (8%) pts.
Conclusions
This analysis indicates a predictable and manageable safety profile for afatinib, consistent with the pivotal LL trials, and encouraging efficacy findings in this broad patient population. As expected, TTSP/PFS were longer for pts with ECOG PS 0/1 vs 2, and for pts with Del 19 or L858R mutations, vs those with uncommon mutations, which may be due to the high prevalence (44%) of pts with exon 20 insertions included in this study.
Table: 482P
TTSP, mos | PFS, mos | |||
---|---|---|---|---|
Baseline characteristic (n) | Median | 95% CI | Median | 95% CI |
Line of tx | ||||
1 (374) | 15.6 | 14.1, 18.5 | 13.8 | 12.6, 15.2 |
2 (81) | 14.7 | 11.3, 20.6 | 13.2 | 8.3, 17.7 |
≥3 (24) | 8.1 | 3.7, 14.4 | 6.6 | 3.2, 12.6 |
Mutationsa | ||||
Del 19b (232) | 19.3 | 15.6, 21.8 | 15.9 | 13.9, 19.1 |
L858Rb (162) | 14.5 | 12.7, 17.9 | 13.1 | 11.5, 15.2 |
Uc (84) | 7.4 | 5.7, 9.0 | 6.0 | 4.2, 8.1 |
ECOG PS, inc. mutations | ||||
0–1 (442)a | 15.8 | 14.4, 18.8 | 13.8 | 12.8, 15.2 |
Cb (364) | 18.2 | 15.5, 19.8 | 15.2 | 13.8, 17.7 |
U (77) | 7.4 | 5.7, 9.7 | 6.6 | 4.6, 8.2 |
2 (36) | 8.9 | 5.7, 13.2 | 6.2 | 2.5, 11.6 |
Cb (30) | 8.9 | 5.7, 13.9 | 7.7 | 3.9, 13.2 |
U (6) | 7.0 | 0.9, 13.0 | 1.4 | 0.4, 6.0 |
Brain metsa | ||||
No (395) | 15.8 | 14.1, 18.8 | 13.9 | 12.7, 15.5 |
Yes (83) | 13.7 | 9.7, 17.2 | 10.1 | 8.2, 13.9 |
Missing n = 1.
bDel 19/L858R only.
cIncludes, n (%): ex 20 ins: 37 (44).
Clinical trial identification
NCT01853826.
Editorial acknowledgement
Christina Jennings 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. M. Hochmair: 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; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Speaker Bureau / Expert testimony: Pfizer. M.R. Migliorino: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: B.I.; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: ROCHE; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: PFIZER. G.Z. Mukhametshina: Advisory / Consultancy: Association of oncologists of Russian Federation; Full / Part-time employment: State Autonomous Healthcare Institution «Republican Clinical Oncology Dispensary of the Ministry of Health of the Republic of Tatarstan». M. Schumacher: Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: AstraZeneca. S. Novello: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: BI; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: AbbVie; Advisory / Consultancy, Speaker Bureau / Expert testimony: Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda. R. Dziadziuszko: Honoraria (self): Pfizer; Honoraria (self): Boehringer Ingelheim; Honoraria (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Travel / Accommodation / Expenses: Roche; Honoraria (self): MSD; Honoraria (self): Bristol-Myers Squibb. W. Tang: Full / Part-time employment: Boehringer Ingelheim. L. Clementi: Full / Part-time employment: Boehringer Ingelheim Italia SpA. A. Cseh: Full / Part-time employment: Boehringer Ingelheim . All other authors have declared no conflicts of interest.
Resources from the same session
528P - High-biologically effective dose radiotherapy may improve local control of small cell lung cancer patients with brain metastases: A propensity-matching analysis
Presenter: Qingyang Zhuang
Session: Poster display session
Resources:
Abstract
530P - Prognostic value of C-reactive protein, albumin and C-reactive protein to albumin ratio in small cell lung cancer: A meta-analysis
Presenter: Carla Emille Barbon
Session: Poster display session
Resources:
Abstract
531TiP - CANOPY-A: A phase III, placebo-controlled study of canakinumab as adjuvant therapy in patients (pts) with surgically resected NSCLC
Presenter: Byoung Chul Cho
Session: Poster display session
Resources:
Abstract
532TiP - CANOPY-1: A phase III, placebo-controlled study of pembrolizumab (PEM) plus platinum-based doublet chemotherapy (Ctx) with/without canakinumab in untreated patients (pts) with stage IIIB/IIIC-IV NSCLC
Presenter: Daniel Shao Weng Tan
Session: Poster display session
Resources:
Abstract
533TiP - CANOPY-2: A phase III, placebo-controlled study of canakinumab with or without docetaxel in patients (pts) with NSCLC previously treated with PD-(L)1 inhibitors and platinum-based chemotherapy (Ctx)
Presenter: Darren Lim
Session: Poster display session
Resources:
Abstract
534TiP - A randomized phase III study of carboplatin plus nab-paclitaxel with or without nintedanib for NSCLC with IPF (J-SONIC)
Presenter: Kohei Otsubo
Session: Poster display session
Resources:
Abstract
535TiP - Phase II study of atezolizumab for pretreated advanced / recurrent non-small cell lung cancer with idiopathic interstitial pneumonia (TORG1936 / AMBITIOUS study)
Presenter: Satoshi Ikeda
Session: Poster display session
Resources:
Abstract
536TiP - INSIGHT 2: Tepotinib plus osimertinib in patients with EGFR-mutant NSCLC having acquired resistance to EGFR TKIs due to MET-amplification: A phase II trial in progress study
Presenter: James C-H Yang
Session: Poster display session
Resources:
Abstract
YO8 - Carcinosarcoma of the Breast in a Filipino Female: A Case Report
Presenter: Ma. Angelle Lalaine Dantes
Session: Poster display session
Resources:
Abstract
YO9 - Small Malignant Phyllodes Tumor of the Breast with Metastases to the Lung and Bone
Presenter: Gusti Harti
Session: Poster display session
Resources:
Abstract