Table 3.
Summary of clinical trials of afatinib in advanced non-small-cell lung carcinoma (LUX-Lung clinical trial program)
| LUX-Lung trial | Phase | EGFR mutation mandated | Line of treatment | Design | Primary endpoint | Efficacy results | Toxicity results |
|---|---|---|---|---|---|---|---|
| LUX-Lung 1, NCT0065613613,14 | IIb/III | N/R | Third-/fourth-line after patient-based chemotherapy and first-generation EGFR TKI | Afatinib + BSC versus placebo + BSC | Overall survival | Primary endpoint of overall survival not met (median, 10.8 months versus 12.0 months; P=0.74); PFS, 3.3 months in the treatment group versus 1.1 months in the placebo group (P<0.0001); 29 (7%) patients achieved a partial response versus one patient in the placebo group | Diarrhea in 339 (87%) of 390 patients (17% grade 3) and acneiform rash in 305 (78%) patients (14% grade 3) |
| LUX-Lung 2, NCT0052514815 | II | Yes | First-/second-line after chemotherapy only; no prior EGFR TKI | Afatinib monotherapy | Objective response (complete response or partial response) | 70 (66%) of 106 patients harboring the two common activating EGFR mutations (deletion 19 or L858R) had objective antitumor responses, whereas 9 (39%) of 23 patients with less common mutations also had objective responses | The two most common toxicities were diarrhea and rash, with grade 3 events more common in patients receiving 50 mg afatinib daily compared with 40 mg daily |
| LUX-Lung 3, NCT0094965011,12 | III | Yes | First-line | Afatinib versus cisplatin/pemetrexed | PFS | PFS of 11.1 months versus 6.9 months (P=0.001); patients with common EGFR mutations had PFS of 13.6 months versus 6.9 months (P=0.001); response rate, 56% versus 23% (P=0.001) | Diarrhea in 95.2% of patients, (G3 14.4%); rash in 89.1% of patients (G3 16.2%); mucositis in 72.1% (G3 in 8.7%; G4 in 0.4%) and paronychia in 56.8% (G3 in 11.4%) of patients; four deaths in the afatinib group in this study |
| LUX-Lung 4, NCT0071159410 | I/II | N/R | Third-/fourth-line after patient-based chemotherapy and first-generation EGFR TKI | Afatinib monotherapy | Phase I: safety, dose-limiting toxicity; Phase II: objective response (complete response or partial response) | 8.2% had a confirmed partial response. PFS was 4.4 months, whereas median overall survival was 19 months; two patients with acquired T790M mutations had SD for 9 months and 1 month, respectively | The most common afatinib-related toxicities were diarrhea in all patients and rash/acne in 91.9% of patients |
| LUX-Lung 5, NCT0108513638 | III | N/R | Third-/fourth-line after chemotherapy ± first-generation EGFR TKI | Part A: afatinib monotherapy Part B: Afatinib + weekly paclitaxel versus investigators’ choice of chemotherapy | PFS | PFS for afatinib was 3.3 months; 8% overall response rate, with 56% SD at 6 weeks; PFS for EGFR-mutated patients was 4.2 months versus 2.6 months in non-EGFR-mutated patients (n=35) | – |
| LUX-Lung 6, NCT01121393 | III | Yes | First-line | Afatinib versus cisplatin/gemcitabine | PFS | PFS 11.0 versus 5.6 months; hazard ratio, 0.28 (P<0.0001); overall response rate, 66.9% versus 23.0% (P<0.0001); and DCR, 92.6% versus 76.2% (P<0.0001) | ≥G3 drug-related toxicities in 36.0% versus 60.2% of patients in each group; the most common toxicities included rash/acne (14.6%), diarrhea (5.4%); stomatitis/mucositis (5.4%) with afatinib; and neutropenia (17.7%), vomiting (15.9%), and leukopenia (13.3%) with gemcitabine-cisplatin |
| LUX-Lung 7, NCT01466660 | IIb | Yes | First-line | Afatinib versus gefitinib | PFS; DCR | – | – |
| LUX-Lung 8, NCT01523587 | III | N/R | Second-line after patient-based chemotherapy; squamous cell histology | Afatinib versus erlotinib | PFS | – | – |
Abbreviations: BSC, best supportive care; DCR, disease control rate; G3, grade 3; N/R, not recorded; PFS, progression-free survival; EGFR, epidermal growth factor receptor; SD, stable disease; TKI, tyrosine kinase inhibitor.