The irreversible ErbB family blocker, afatinib, is approved for first-line treatment of metastatic NSCLC harbouring non-resistant EGFR mutations. While afatinib has demonstrated a predictable and manageable safety profile in pts with EGFR mutation-positive (EGFRm+) NSCLC, elderly pts are often under-represented in clinical trials. Here, we summarise the current status of, and preliminary data from, an ongoing Phase IV trial of afatinib in elderly pts with Del19/L858R EGFRm+ NSCLC (NCT02514174).
Pts aged ≥70 yrs with Stage IV/recurrent Del19/L858R EGFRm+ NSCLC naïve to prior systemic therapy have been enrolled to sites in the USA. Pts receive afatinib QD (starting dose 30 mg/day) until disease progression/intolerable AEs. Dose reduction to 20 mg/day is permitted in the case of select Grade 2/≥3 AEs. The primary endpoint is the occurrence of AEs leading to dose reduction. Secondary endpoints include occurrence of Grade ≥3 diarrhoea and Grade ≥3 rash/acne, stomatitis and paronychia (grouped terms). Other endpoints are AEs by NCI CTCAE grade, objective response (OR), PFS and overall survival. Preliminary safety data are reported here.
As of 7 Feb 2018, 26 pts have been enrolled across 9 sites, and 24 pts have entered into the trial. Twenty-three pts have been treated: 57% female; 30% Asian; 26%/74% ECOG PS 0/1; median age (range) 79 (71–93) yrs. Thirteen (57%) pts remain on treatment. Reasons for treatment discontinuation were progressive disease (26%), AEs (9%), refusal to continue study medication (4%), and other (4%). All pts have had at least one AE of any cause (Grade 3/4: 52%/0%), most commonly (preferred term [PT]) diarrhoea (87%), rash (61%) and fatigue (48%). The most common treatment-related AEs (PTs) reported are diarrhoea (83%), rash (57%) and dry skin (39%), and the most common serious AEs (PTs) reported are vomiting and dehydration (both 9%). Ten (43%) pts have achieved confirmed OR (complete/partial response: 1 [4%]/9 [39%]) and 10 (43%) pts have had stable disease.
In this preliminary analysis, afatinib (30 mg/day) demonstrated a predictable safety profile in pts aged ≥70 yrs with Del19/L858R EGFRm+ NSCLC. Updated data will be presented.
Clinical trial identification
Legal entity responsible for the study
Laura Winton of GeoMed, an Ashfield company, part of UDG Healthcare plc.
K.L. Reckamp: Consulting fees: Takeda, Tesaro, Euclises, and Boehringer Ingelheim. B. Halmos: Consulting fees, grants/funds: Boehringer Ingelheim, AstraZeneca, Takeda, Eli Lilly, Pfizer, Novartis; Consulting fees: Roche/Genentech, Foundation Medicine, Guardant Health; Grant/funds: Merck, Mirati, Eisai, Genentech. M. Jahanzeb: Grant funding: Boehringer Ingelheim. L.C. Seneviratne: Consulting fees and Honoraria for a Speaker's bureau: Novartis. J.A. Wallace: Honoraria: Genentech. B. Rueter, E. Dowling: Employee: Boehringer Ingelheim. A. Esler: Contracted: Boehringer Ingelheim. M. Koczywas: Honoraria for a Speaker bureau: AstraZeneca. All other authors have declared no conflicts of interest.