LUX-Lung 5 – Afatinib* Plus Weekly Paclitaxel vs Investigator's Choice of Single Agent Chemotherapy Following Afatinib Monotherapy in Non-⁠Small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib

Phase III randomised trial of afatinib plus weekly paclitaxel vs investigator's choice of chemotherapy (ICC) following afatinib monotherapy in patients with non-small cell lung cancer (NSCLC) who had failed at least one line of chemotherapy and erlotinib or gefitinib treatment.

Trial CTgov-Identifier: NCT01085136


Failed treatment with ≥1 line of chemotherapy
Progression after erlotinib or gefitinib
Stable disease, progressive disease or complete response as best response to taxane-based chemotherapy
≥12 weeks clinical benefit on afatinib monotherapy
Eastern Cooperative Oncology Group performance status 0–2

N = 1,154

Randomisation 2:1

  • Afatinib 40 mg
    Oral once daily
    Paclitaxel 80 mg/m2

  • ICC single-agent


Primary Outcome Measures:
Progression-free survival (PFS) time as determined by Response Evaluation Criteria in Solid Tumors 1.1
Secondary Outcome Measures:
Overall survival (OS)
Objective response rate (ORR)
Health-related quality of life (HRQoL)


Patients who failed prior chemotherapy and a first-generation TKI, and who continued afatinib treatment plus paclitaxel after progressing on afatinib alone, had a significant PFS benefit compared with the group that received ICC only. ORR was superior with afatinib plus paclitaxel vs ICC (32.1% vs 13.2%, p=0.005) OS was similar in both arms (12.2 vs 12.2 months).

Primary End Point: PFS by Investigator Review

The most common drug-related adverse events (AEs) observed in the afatinib treatment arm were diarrhoea (53.8%), alopecia (32.6%), and asthenia (27.3%).


LUX-Lung 5 demonstrated that in clinically selected patients, continuous ErbB blockade with afatinib in patients with NSCLC failing chemotherapy, erlotinib/gefitinib and following afatinib monotherapy, improves PFS and ORR.

The AE profile of afatinib + paclitaxel was consistent with previous studies, including LUX-Lung 1,LUX-Lung 3,LUX-Lung 4 and LUX-Lung 6. Frequency and severity of AEs did not impact Global Health Status (as an overall indicator of overall HRQoL).

LUX-Lung 5 is the first prospective, randomised trial demonstrating the benefit of continuous blockade of oncogenic EGFR signalling (treatment beyond progression) with afatinib in patients with NSCLC previously treated with EGFR tyrosine kinase inhibitors.


Schuler M, Chih-Hsin Yang J et al. Afatinib beyond progression in patients with non-small-cell lung cancer following chemotherapy, erlotinib/gefitinib and afatinib: phase III randomized LUX-Lung 5 trial. Ann Oncol 2016;27(3):417-423. (Accessed: May 2016).