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
313P - Immunotherapy application for advanced cancers: One institution experiences since 2016 to 2019
Presenter: Jo Pai Chen
Session: Poster display session
Resources:
Abstract
314P - An EGF motif of Del1 inhibits efficient angiogenesis and suppresses tumour growth in vivo
Presenter: Hisataka Kitano
Session: Poster display session
Resources:
Abstract
315P - Inhibition of JAK1 sensitizes human head and neck cancer cells to cetuximab
Presenter: James Bonner
Session: Poster display session
Resources:
Abstract
316TiP - Neoadjuvant and adjuvant pembrolizumab (pembro) plus standard of care (SOC) in patients (pts) with resectable locally advanced (LA) head and neck squamous cell carcinoma (HNSCC): The phase III KEYNOTE-689 study
Presenter: Ezra Cohen
Session: Poster display session
Resources:
Abstract
322P - Three-year overall survival update from the PACIFIC trial
Presenter: Yi-Long Wu
Session: Poster display session
Resources:
Abstract
323P - Novel tumour mutation score versus tumour mutation burden in predicting survival after immunotherapy in pan-cancer from MSK-IMPACT cohort
Presenter: Yuan Li
Session: Poster display session
Resources:
Abstract
324P - A novel anti-PD-1 antibody HLX10 study led to the initiation of combination immunotherapy
Presenter: Tsu Yi Chao
Session: Poster display session
Resources:
Abstract
325P - Association between immune-related adverse events and efficacy of immune checkpoint inhibitors in patients with advanced hepatocellular carcinoma
Presenter: Lawrence Wong
Session: Poster display session
Resources:
Abstract
326P - Autologous V gamma 9 V delta 2 T cell therapy to target Epstein Barr Virus (EBV)-related malignancies
Presenter: Esdy Rozali
Session: Poster display session
Resources:
Abstract
327P - Neoantigen profile of hepatocellular carcinoma reveals its correlation with tumour progression and clonal evolution
Presenter: Xiaolong Liu
Session: Poster display session
Resources:
Abstract