Abstract 4178
Background
Primary LL8 data showed significantly improved PFS and OS with afatinib compared with erlotinib as second-line treatment in pts with lung SCC, leading to the approval of afatinib in this setting. As previously reported (data cut-off: Apr 2015), PFS (2.6 vs 1.9 months; HR 0.81 [95% CI 0.69–0.96]; p = 0.01), objective response rate (ORR; 5.5 vs 2.8%; p = 0.06) and disease control rate (DCR; 50.5 vs 39.5%; p = 0.002) were higher with afatinib vs erlotinib. PFS and OS benefits on afatinib appeared even greater for pts with ErbB mutation-positive tumours vs ErbB wild-type tumours. Here we present the final analysis of OS and safety data. Other efficacy endpoints were not updated; as of Apr 2015, only 9 (1%) pts remained on treatment, so minimal changes would be expected.
Methods
This open-label, multicentre, Phase III trial enrolled pts with stage IIIB/IV lung SCC who had progressed on ≥ 4 cycles of platinum-based chemotherapy. Pts were randomised 1:1 to receive afatinib (40 mg/day) or erlotinib (150 mg/day) until progression. Primary endpoint was PFS by independent radiological review. The key secondary endpoint was OS; other endpoints included ORR, DCR and safety.
Results
795 patients were included (398 on afatinib; 397 on erlotinib). Baseline characteristics were well balanced between arms. Updated OS (data cut-off: Mar 2018) was significantly longer for afatinib than erlotinib (7.8 vs 6.8 months; HR 0.84 [95% CI 0.73–0.97]; p = 0.019). Overall AE profile was comparable between arms: 57.4% of afatinib and 57.5% of erlotinib pts reported AEs ≥grade 3 (G3); serious AEs were reported for 44.4% and 44.3% of pts, respectively. A higher incidence of drug-related ≥G3 diarrhoea (10.5 vs 2.5%) and G3 stomatitis (4.1 vs 0%) was reported on afatinib, and a higher incidence of G3 rash/acne was reported on erlotinib (5.9 vs 10.4%). AEs leading to treatment discontinuation were comparable across arms (20.4 vs 16.7%). Updated data on pts with long-term disease control (treatment ≥1 year) will be presented.
Conclusions
Results are consistent with those previously reported for LL8. Updated OS was significantly greater for afatinib than erlotinib. The AE profile was comparable across arms and manageable.
Clinical trial identification
NCT01523587.
Legal entity responsible for the study
Boehringer Ingelheim.
Funding
Boehringer Ingelheim.
Editorial Acknowledgement
Christina Jennings of GeoMed, an Ashfield company, part of UDG Healthcare plc.
Disclosure
G.D. Goss: Speaker bureau: AstraZeneca, BMS, Pfizer, Celgene. A. Morabito: Honoraria: Roche, AstraZeneca, Boehringer, Pfizer, BMS, MSD. A. Ardizzoni: Membership on an advisory board or board of directors: MSD Corporate-sponsored research: BMS, Celgene. A. Cseh: Employment: Boehringer Ingelheim RCV GmbH & Co. KG. S. Bender: Employment: Boehringer Ingelheim Pharmaceuticals, Inc. E. Felip: Advisory Board: Eli Lilly, Pfizer, Roche, MSD, Boehringer Ingelheim; Lecture Fees: AstraZeneca, BMS, Novartis. All other authors have declared no conflicts of interest.
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