4132 - Phase IV, open-label, multicentre trial of afatinib in patients (pts) aged _70 yrs with NSCLC harbouring common (Del19/L858R) EGFR mutations: preliminary results

Background

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).

Methods

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.

Results

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.

Conclusions

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

NCT02514174.

Legal entity responsible for the study

Boehringer Ingelheim.

Funding

Boehringer Ingelheim.

Editorial Acknowledgement

Laura Winton of GeoMed, an Ashfield company, part of UDG Healthcare plc.

Disclosure

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.