Afatinib in Non-Small Cell Lung Cancer Harboring Uncommon EGFR Mutations Pretreated With Reversible EGFR Inhibitors.
BACKGROUND
Afatinib, an irreversible ErbB family blocker, is approved for treatment of patients with previously untreated non-small cell lung cancer (NSCLC) harboring activating epidermal growth factor receptor (EGFR) mutations. Efficacy of afatinib in EGFR tyrosine kinase inhibitor-naïve (TKI-naïve) patients with uncommon EGFR mutations (other than exon 19 deletions or exon 21 point mutations) has been reported; however, efficacy in TKI-pretreated patients with uncommon EGFR mutations is unknown.


METHODS
In the afatinib compassionate use program (CUP), patients with advanced or metastatic, histologically confirmed NSCLC progressing after at least one line of chemotherapy and one line of EGFR-TKI treatment were enrolled. Demographic data, mutation type, response rates, time to treatment failure (TTF), and safety in patients harboring uncommon EGFR mutations were reported.


RESULTS
In 60 patients (63% female, median age 63 years [range: 30-84 years]), a total of 66 uncommon EGFR mutations including 30 T790M mutations were reported (18.4% and 11%, respectively, of known EGFR mutations within the CUP). Most patients (67%) received afatinib as third- or fourth-line treatment. Median TTF was 3.8 months (range: 0.2 to >24.6 months; p = .244) in patients with uncommon mutations compared with 5.1 months (range: 0.1 to >21.1 months) in patients with common mutations (n = 165). Pronounced activity was observed with E709X mutations (TTF >12 months). No new safety signals were detected.


CONCLUSIONS
Afatinib is clinically active and well tolerated in many TKI-pretreated NSCLC patients harboring uncommon EGFR mutations. Compared with results reported in TKI-naïve patients, activity was also indicated in patients with T790M and exon 20 insertion mutations.
LungenClinic Grosshandsdorf, Thoracic Oncology, German Center for Lung Research, Grosshansdorf, Germany.
David F
DF
Heigener
Clinic for Pulmonary, Thoracic Oncology, Sleep and Respiratory Critical Care, Kempten-Oberallgaeu Hospitals GmbH, Immenstadt, Germany.
Christian
C
Schumann
Department of Medicine II, University Hospital Frankfurt, Frankfurt, Germany.
Martin
M
Sebastian
Clinic for Hematology, Oncology and Palliative Medicine, Minden, Germany.
Parvis
P
Sadjadian
Department of Internal Medicine V, University Hospital of the Saarland, Homburg, Germany.
Ingo
I
Stehle
Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Angela
A
Märten
Department Hematology and Oncology, Pius-Hospital Oldenburg, University Department of Internal Medicine-Oncology, Medical Campus, University of Oldenburg, Oldenburg, Germany.
Anne
A
Lüers
Department Hematology and Oncology, Pius-Hospital Oldenburg, University Department of Internal Medicine-Oncology, Medical Campus, University of Oldenburg, Oldenburg, Germany.
Frank
F
Griesinger
Department of Internal Medicine I, Center for Integrated Oncology, University of Cologne, Cologne, Germany.
Matthias
M
Scheffler
D000328:Adult; D000077716:Afatinib; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D057176:Compassionate Use Trials; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000077716:Afatinib; C512478:EGFR protein, human; D066246:ErbB Receptors
Afatinib; Compassionate use trials; Epidermal growth factor receptor; ErbB receptors; Non-small cell lung cancer