Table 1.
Selected clinical efficacy reports of third-generation EGFR-TKIs
| Drug name | Number | Patient group | Dose | ORR | PFS | AEs (% total, % ≥ grade 3)a | ILD (%) | Distinct AEs |
|---|---|---|---|---|---|---|---|---|
| Osimertinib | 411 | EGFR-TKI pretreated advanced EGFR T790M–positive NSCLC | 80 mg/day | 66% (95% CI, 61–71) | 11.0 months (95% CI 9.6–12.4) | Skin rash (41, < 1), diarrhea (38, < 1), dry skin (30, 0), QTc prolongation (3, 1) | 3 | Neutropenia, lymphopenia, thrombocytopenia, hyponatremia, QTc prolongation |
| Rociletinib | 548 | EGFR-TKI pretreated advanced EGFR T790M–positive NSCLC | 500–750 mg twice per day | 33.9% (95% CI, 29.5–38.5) | 5.7 months (95% CI 4.2–6.2) at 500 mg twice a day | Hyperglycemia (65.2, 35.2), skin rash (11.7, 0.4), diarrhea (57.5, 4.6), QTc prolongation (30.1, 10.2) | 2.4 | Hyperglycemia, cataract, QTc prolongation, pancreatitis |
| Olmutinib | 76 | EGFR-TKI pretreated advanced EGFR T790M–positive NSCLC | 800 mg/day | 54% | 6.9 months(95% CI 5.36–9.49) | Diarrhea (59, 0), pruritus (42, 1), rash (41, 5), nausea (39, 0), Palmar-plantar erythrodysesthesia syndrome (30, 4) | 1 | Palmar-plantar erythrodysesthesia syndrome |
| EGF816 | 152 | Advanced EGFR mutation-positive NSCLCb | 75–350 mg/day | 46.9% (95% CI, 38.7–55.3) | 9.7 months (95% CI 7.3–11.1) | Skin rash (53.9, 16.4), diarrhea (36.8, 2), pruritus (34.2, NA), dry skin (25.0, NA), stomatitis (24.3, 2.0) | 0.7 | Distinct skin rash, hepatitis B virus reactivation, increased serum lipase level |
| ASP8273 | 63 | Advanced EGFR mutation-positive NSCLC (92% harbored EGFR T790M) | 300 mg/day | 30% (95% CI, 19.2–43.0) | 6.0 months (95% CI 4.1–9.8) | Diarrhea (48, 2), nausea (27, 0), paresthesia (14, 0), vomiting (13, 0), dizziness (11, 0), and hyponatremia (19, 13) | 0 | Hyponatremia, paresthesia |
Abbreviations: EGFR epidermal growth factor receptor, TKI tyrosine kinase inhibitor, ORR objective response rate, PFS progression-free survival, AE adverse event, ILD interstitial lung disease, NSCLC non-small cell lung cancer, CI confidence interval, QTc QT interval corrected for heart rate, NA not available
aFor each AE, reported values in this column are (the percent of patients receiving the therapy who experience the AE, the percent of patients receiving the therapy who experienced the AE at grade ≥ 3)
bIncluding patients harbored sensitizing EGFR mutations following EGFR-TKI therapy (regardless of EGFR T790M status), EGFR exon 20 insertion or deletion, de novo T790M mutation, and patients with treatment-naïve advanced EGFR mutation-positive NSCLC