P3.02b-046 Afatinib Benefits Patients with Confirmed/Suspected EGFR Mutant NSCLC, Unsuitable for Chemotherapy (TIMELY Phase II Trial): Topic: EGFR Clinical

Afatinib is licensed for EGFR-mutant NSCLC without prior TKI therapy, but its efficacy and toxicity in patients unsuitable for platinum-doublet chemotherapy is unknown. One previous study suggested that TKIs could benefit medically unfit EGFR-mutant East Asian patients. We conducted the first such study in a Western population. Single arm phase-II trial. Eligible patients with histologically confirmed NSCLC, comorbidities precluding chemotherapy, with either: (i) confirmed EGFR-mutation and PS 0-3, or (ii) suspected EGFR-mutation (no suitable tissue for genotyping or failed genotyping), but never/former-light smoker, adenocarcinoma and PS 0-2. Patients received oral afatinib (20-40mg daily) until disease progression/toxicity. CT scans performed 4 weeks after starting treatment then every 8 weeks in first year until progression, thereafter every 12 weeks. Primary endpoint was 6-month RECIST-defined progression-free-survival (target 30%). 39 patients were recruited across 14 UK centers (March 2013-August 2015). Median age 72 years (range 36-90); 30 females, 9 males; 20 confirmed and 19 suspected EGFR-mutant; 8 former and 11 never smokers (among suspected EGFR-positives); 1,1,7,30 in each stage IA,IIIA,IIIB,IV; and 27 PS 0-1, 12 PS 2-3. As of July 2016, 7 patients were still taking afatinib (median time on drug 11 months, range 10-16), and 11 stopped for toxicity. 23/39 patients had at least one grade ≥3 afatinib-related toxicity (all gd3, except two with gd4 [sepsis and hypokalemia], one fatal pneumonitis), mainly: n=13 diarrhea; n=4 vomiting; n=3 dehydration; n=3 mouth ulcer, all expected for afatinib, and unsurprising in this unfit group. The table shows efficacy. 6-month PFS rate (58%) far exceeded the 30% target; similarly for patients with confirmed (74%) or suspected (41%) EGFR-mutation.Tabled 1Efficacy (26 PFS events, 21 deaths)Rate (95%CI) at monthAlive & progression-freeOverall-survivalAll patients (n=39)658% (43-74)74% (60-88)1234% (18-50)64% (48-80)Median, months (95%CI)7.9 (4.6-10.2)15.5 (10.9-25.1)Confirmed EGFR mutant (n=20)674% (55-94)85% (69-100)1247% (24-70)85% (69-100)Median, months10.2 (5.9-not estimable)Not reachedSuspected EGFR mutant (n=19)641% (19-64)63% (41-85)1221% (0.1-41)42% (18-66)Median, months4.4 (2.6-8.0)10.9 (3.9-21.0)Lower 95%CI for all 6-month PFS-rates exceed the pre-specified 15% minimum rate.13% patients survived ≥18 months. 23% patients did not progress <12 months Open table in a new tab The toxicity rate was higher compared to that in fitter patients, but afatinib seems to improve PFS and OS in unfit EGFR-mutant NSCLC, and in suspected-positive patients who would otherwise only receive best supportive care.