Abstract 1341P
Background
Uncommon EGFR mutations show heterogeneity in their EGFR TKI sensitivities.1 Afatinib has shown broad inhibitory activity against uncommon mutations in vitro,1 and clinical activity against major uncommon mutations (G719X/L861Q/S768I).2 However, clinical data regarding the efficacy of afatinib against other uncommon EGFR mutations is lacking, particularly between ethnicities.
Methods
This pooled analysis assessed afatinib activity in Asian/non-Asian, EGFR TKI-naïve pts with NSCLC and uncommon EGFR mutations, treated in RCTs and real-world studies. Uncommon mutations were classed as: de novo T790M; exon 20 insertions (Ins20); major uncommon mutations (G719X/L861Q/S768I); compound mutations (≥2 uncommon mutations); and other uncommon mutations. Key endpoints were objective response rate (ORR), duration of response (DoR), and time to treatment failure (TTF).
Results
Of the 178/120 Asian/non-Asian pts with uncommon EGFR mutations, 62/35% had a major uncommon mutation and 16/39% had an Ins20 mutation. Clinical activity (Asian/non-Asian) was observed against major uncommon mutations (ORR: 66/59%; median DoR: 14.7/15.9 mos) compound mutations (ORR: 81/100%; median DoR: 11.5/18.6 mos) and other uncommon mutations (ORR: 79/60%; median DoR: 9.0/10.7 mos). Some pts with Ins20 responded (21/23%). TTF was longest in pts with compound mutations, particularly amongst non-Asian pts (median 18.5 mos). Overall, 3.1/3.5% of Asian/non-Asian pts were long-term responders (treated ≥3 years).
Conclusions
Afatinib is effective in pts with NSCLC harboring major uncommon and compound EGFR mutations, with broad activity against other uncommon EGFR mutations and some Ins20 mutations, unaffected by ethnicity. Asian pts appeared to have a high proportion of major uncommon mutations, known to be highly sensitive to afatinib.2 1. Kohsaka S, et al. Sci Transl Med 2017;9:eaan6566. 2. Yang JC, et al. Lancet Oncol 2015;16:830‒8 Table: 1341P
| Patients*, n (%) | ORR, % | DoR, months (95% CI) | TTF, months (95% CI) | |||||
| Asian (N=178) | Non-Asian (N=120) | Asian | Non-Asian | Asian | Non-Asian | Asian | Non-Asian | |
| Major uncommon | 110 (61.8) | 42 (35.0) | 66 | 59 | 14.7 (11.5–17.1) | 15.9 (8.1–18.7) | 11.5 (11.5–13.8) | 9.0 (4.6–15.4) |
| Compound | 26 (14.6) | 8 (6.7) | 81 | 100 | 11.5 (11.5–17.1) | 18.6 (18.5–18.7) | 11.5 (8.2– 16.6) | 18.5 (1.6–NR) |
| Ins20 | 29 (16.3) | 47 (39.2) | 21 | 23 | 11.0 (5.4–NR) | 10.7 (1.6–26.7) | 4.5 (2.6–5.4) | 3.9 (2.8–5.4) |
| Any de novo T790M | 19 (10.7) | 14 (11.7) | 38 | 17 | 8.1 (3.8–13.8) | 7.4 (3.7–11.0) | 4.7 (1.2–5.5) | 2.9 (0.9–6.7) |
| Others | 17 (9.6) | 13 (10.8) | 79 | 60 | 9.0 (2.0–14.7) | 10.7 (3.5–24.0) | 7.2 (1.8–11.9) | 10.7 (2.0–24.0) |
*patients may be included in >1 group.
.Clinical trial identification
N/A
Editorial acknowledgement
Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Nadia Fowler, of GeoMed, an Ashfield company, part of UDG Healthcare plc, during the preparation of this abstract.
Legal entity responsible for the study
Boehringer Ingelheim.
Funding
Boehringer Ingelheim.
Disclosure
J.C-H. Yang: Honoraria (institution), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (institution), Advisory/Consultancy: Novartis; Honoraria (institution), Advisory/Consultancy: AstraZeneca; Honoraria (institution), Advisory/Consultancy: Roche/Genentech; Honoraria (institution), Advisory/Consultancy: Lilly; Honoraria (institution), Advisory/Consultancy: MSD Oncology; Honoraria (institution), Advisory/Consultancy: Merck Serono; Honoraria (institution), Advisory/Consultancy: Celgene; Honoraria (institution), Advisory/Consultancy: Bayer; Honoraria (institution), Advisory/Consultancy: Pfizer; Honoraria (institution), Advisory/Consultancy: Ono Pharmaceutical; Honoraria (institution), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (institution), Advisory/Consultancy: Yuhan; Honoraria (institution), Advisory/Consultancy: Hansoh; Honoraria (institution), Advisory/Consultancy: Brueprint Medicines; Honoraria (institution), Advisory/Consultancy: Daiichi Sankyo; Honoraria (institution), Advisory/Consultancy: Amgen; Honoraria (institution), Advisory/Consultancy: Takeda Oncology; Honoraria (institution), Advisory/Consultancy: Incyte; Honoraria (institution), Advisory/Consultancy: H: Boehringer Ingelheim; Honoraria (institution), Advisory/Consultancy: Roche; Honoraria (institution), Advisory/Consultancy: MSD; Honoraria (institution), Advisory/Consultancy: Eli Lilly. M. Schuler: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Honoraria stand for honoraries for CME presentations: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Honoraria stand for honoraries for CME presentations: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Honoraria stand for honoraries for CME presentations: Novartis; Advisory/Consultancy: Roche; Advisory/Consultancy: Takeda; Honoraria (self), Honoraria stand for honoraries for CME presentations: MSD; Honoraria (self), Honoraria stand for honoraries for CME presentations: Pierre Fabre. S. Popat: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): BMS; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Takeda; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AZ; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MSD; Honoraria (self), Advisory/Consultancy: EMD Serono; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Guardant Health; Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Boheringer Ingelheim; Honoraria (self), Advisory/Consultancy: Incyte; Honoraria (self), Advisory/Consultancy: Paradox; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Ariad. S. Miura: Advisory/Consultancy, Speaker Bureau/Expert testimony: Chugai Pharma; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Speaker Bureau/Expert testimony: Boehringer Ingelheim; Speaker Bureau/Expert testimony: Taiho Pharma; Speaker Bureau/Expert testimony: Ono Pharmaceutical; Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: AbbVie; Speaker Bureau/Expert testimony: Kyowa Hakko Kirin . S. Heeke: Honoraria (self): Boehringer Ingelheim; Honoraria (self): Qiagen; Travel/Accommodation/Expenses: Roche. A. Passaro: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Dako. K. Park: Advisory/Consultancy: Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): AZ; Advisory/Consultancy, Speaker Bureau/Expert testimony: BI; Advisory/Consultancy: BMS; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: JNJ; Advisory/Consultancy: Merck KGaA; Advisory/Consultancy, Research grant/Funding (self): MSD; Advisory/Consultancy: Roche. E.S. Kim: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Merck; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Takeda; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer. All other authors have declared no conflicts of interest.