107PD - Afatinib (A) plus paclitaxel (P) following progression on A monotherapy in patients (pts) with metastatic non-small-cell lung cancer (NSCLC) who pre...

Date 16 April 2015
Event ELCC 2015
Session Advanced NSCLC
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Presenter Martin Schuler
Citation Annals of Oncology (2015) 26 (suppl_1): 29-44. 10.1093/annonc/mdv050
Authors M. Schuler1, J.C. Yang2, K. Park3, V.K. Chand4, B. Wang5, D. Planchard6
  • 1West German Cancer Center, University Duisburg-Essen, 45147 - Essen/DE
  • 2Department Of Oncology, National Taiwan University, Taipei/TW
  • 3Division Of Hematology/oncology, Samsung Medical Center, Seoul/KR
  • 4Clinical Development Medical Affairs – Oncology, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield/US
  • 5Biostatistics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield/US
  • 6Department Of Medical Oncology (thoracic Unit) And Translational Research, Gustave Roussy, Villejuif/FR



A confers clinical benefit in pts with NSCLC progressing after treatment with E/G. This phase III trial prospectively assessed whether continued irreversible ErbB-family blockade with A combined with P has superior outcomes vs switching to investigator choice single agent chemotherapy (CT) alone in pts acquiring resistance to E/G and A monotherapy.


Pts who failed ≥1 line of CT, E/G and thereafter A (50 mg/day), each TKI after ≥12 weeks of benefit, were randomised 2:1 to receive A + P (40 mg/day; 80 mg/m2/week) or single-agent CT. Primary endpoint: progression-free survival (PFS). Additional endpoints included objective response rate (ORR), overall survival (OS), safety, and patient-reported outcomes.


1,154 pts were treated with A (50 mg/day). From this population, 202 consenting pts who had derived ≥12 weeks of benefit on A were randomised to A + P (n = 134) or CT (n = 68). PFS (median 5.6 vs 2.8 months; p = 0.003) and ORR (32.1% vs 13.2%; p = 0.005) significantly improved with A + P. There was no significant difference in median OS (12.2 vs 12.2 months; p = 0.994). This could reflect differences in post-progression treatment between arms. Pts were on ≥4th line of therapy at randomisation to A + P or CT, and approximately 60% of pts received ≥1 subsequent therapy post-progression. More patients in the CT arm received two additional lines of therapy than in the A + P arm (36% vs 15%). Treatment-related adverse events (AEs) were consistent with those previously reported with each agent. Most common were (A + P vs CT) diarrhoea (53.8% vs 6.7%), alopecia (32.6% vs 15.0%) and asthenia (27.3% vs 28.3%). Global health status/QoL was maintained with A + P despite prolonged exposure (133 vs 51 days for CT). There was a trend towards prolonged time to deterioration for dyspnoea and pain, but not cough, with A + P vs CT.


A + P improved outcomes in pts who acquired resistance to E/G and progressed on A after initial benefit. LL5 is the first prospective trial to demonstrate the benefit of continued exposure to an ErbB TKI post progression, vs switching to single-agent CT.

Clinical trial identification NCT01085136; October 1, 2014.


M. Schuler: Prof. Schuler reports advisory board participation for, and corporate sponsored research from, Boehringer Ingelheim.

J.C.-H. Yang: Prof. Yang reports advisory board participation for Boehringer Ingelheim, Pfizer, Novartis, AstraZeneca, Roche/Genentech, Clovis Oncology, MSD, Merck Serono and Eli Lilly; and corporate sponsored research from Boehringer Ingelheim.

K. Park: Prof. Park reports advisory board participation for AstraZeneca, Boehringer Ingelheim, Clovis, Daiichi Sankyo, Eli Lilly, Hanmi, Kyowa Hakko Kirin, Novartis, Ono and Roche; and corporate-sponsored research from AstraZeneca and Sanofi Aventis.

V.K. Chand: Dr Chand is an employee of Boehringer Ingelheim and reports that Boehringer Ingelheim sponsored the LUX-Lung 8 trial.

B. Wang: Dr Wang is an employee of Boehringer Ingelheim.

D. Planchard: Dr Planchard reports advisory board participation for Boehringer Ingelheim, Roche and AstraZeneca.