Article Figures & Data
Figures
- Figure 1.
Molecular subsets of lung cancer.
- Figure 2.
Treatment algorithm in first-line metastatic non-small-cell lung cancer (NSCLC). EGFR, epidermal growth factor receptor; PS, performance status; TKI, tyrosine kinase inhibitor; WT, wild-type.
- Figure 3.
ALK-positive fluorescence in situ hybridization image of a patient with non-small-cell lung cancer.
- Figure 4.
Cutaneous toxicities, or “skin rash”, caused by tyrosine kinase inhibitors in patients with non-small-cell lung cancer.
Tables
- Table 1. Randomized Studies Comparing Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors and Chemotherapy in First-Line Treatment of Non-Small-Cell Lung Cancer
Study TKI EGFR mutations (n) ORR (TKI vs CT) (%) Median PFS (TKI vs CT) (months) OS (TKI vs CT) (months/HR) First-Signal Gefitinib 27 84 vs 37 8.4 vs 6.7 30.6 vs 26.5 IPASS Gefitinib 132 71 vs 47 9.8 vs 6.4 21.6 vs 21.9 NEJGSG002 Gefitinib 228 74 vs 29 10.8 vs 5.4 27.7 vs 26.6 WJTOG3405 Gefitinib 172 62 vs 32 9.2 vs 6.3 NA OPTIMAL Erlotinib 154 83 vs 36 13.7 vs 4.6 NA EURTACC Erlotinib 173 58 vs 15 9.7 vs 5.2 NA Lux-Lung 3 Afatinib 308 56 vs 23 13.6 vs 6.9 HR: 1.12 Lux-Lung 6 Afatinib 364 67 vs 23 11 vs 5.6 HR: 0.95 CT, chemotherapy; EGFR, epidermal growth factor receptor; HR, hazard ratio; NA, not available; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; TKI, tyrosine kinase inhibitor.
Study Phase Patients with NSCLC, AKT+ (n) ORR (%) PFS (months) Author PROFILE 1001 Phase I 149 60.8 (95% CI, 52.3–68.9) 9.7 (95% CI, 7.7–12.8) Camidge 2012 PROFILE 1005 Phase II 261 60 (95% CI, 53.6–65.9) 8.1 (95% CI, 6.8–9.7) Kim 2012 PROFILE 1007 Phase III (CZT vs pemetrexed/docetaxel) 346 65 vs. 19.5* 7.7 vs 3.0* Shaw 2013 PROFILE 1014 Phase III (CZT vs cisplatin or carboplatin + pemetrexed) 343 74 vs. 45* 10.9 vs 7.0* Mok 2014 ↵* P < .0001.
CZT, crizotinib; CI, confidence interval; NA, not available; NSCLC, Non-small-cell lung cancer; ORR, objective response rate; PFS, progression-free survival.
- Table 3. Common Toxicities With Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors
Adverse Events Gefitinib Erlotinib Afatinib NEJSG002 IPASS First-SIGNAL WJTOG3405 OPTIMAL EURTAC LUX-LUNG 3 Grade 1–4 Grade >3 Grade 1–4 Grade >3 Grade 1–4 Grade >3 Grade 1–4 Grade >3 Grade 1–4 Grade >3 Grade 1–4 Grade >3 Grade 1–4 Grade >3 Rash 71 5 66 3 72 29 85 1 73 2 80 13 89 16 Diarrhea 34 1 46 4 50 2 54 1 25 1 57 5 95 14 Fatigue 10 2 17 1 28 10 39 1 5 0 57 6 17 1 Stomatitis NA NA 17 1 40 2 22 0 13 1 NA NA 70 9 Vomiting NA NA 13 1 19 0 NA NA 1 0 NA NA 17 3 AST/ALT elevation 54 26 NA NA 30 11 70 27 37 4 6 2 NA NA Data are percentages.
ALT, alanine transaminase; AST, aspartate transaminase; NA, not available.
Histological Subtype Targets Drugs Non squamous-cell carcinoma Anti-EGFR (T790 mol/L) AZD-9291 CO-1686 Anti-ALK Ceritinib Anti-MEK Selumetinib Anti-BRAF Dabrafenib Anti-HER2 Trastuzumab Pertuzumab Anti-MET Onartuzumab Tivantinib Cabozantinib Crizotinib Anti-RET Cabozantinib Squamous-cell carcinoma Anti-EGFR Necitumumab Anti-FGFR1 Ponatinib Dovitinib Cediranib Anti-DDR2 Dasatinib
