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%).


      Tabled 1
      Efficacy (26 PFS events, 21 deaths)
      Rate (95%CI) at monthAlive & progression-freeOverall-survival
      All 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 reached
      Suspected 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


      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.


      NSCLC, afatinib, mutation, EGFR