Table 1.
The summarized targeted therapy studies in NSCLC
| Year | Drug | Type of inhibition | Patient | Company | Recommended dose | Outcomes | Refs. |
|---|---|---|---|---|---|---|---|
| 2011 | Crizotinib | A small molecule TKI | NSCLC with ALK-positive | Pfizer | 250 mg orally twice daily | (ORR) of 61% (95% CI 52%–70%), PFS of 7.7 | [242] |
| 2013 | Erlotinib (tarceva) | EGFR TKI | NSCLC with EGFR exon 19 deletions or exon 21 (L858R) substitution mutations | Astellas Pharma Inc | 150 mg/day | ORR: 65%, PFS: 10.4 months, OS: 22.9 months | [239] |
| 2015 | Gefitinib | Selective small-molecule EGFR TKI | NSCLC with EGFR exon 19 deletions or exon 21 (L858R) substitution mutations | AstraZeneca | 250 mg daily | ORR: 50% (95%CI 41–59), DoR: 6.0 months | [240] |
| 2015 | Osimertinib (TagrissoTM, AZD9291) |
Third-generation EGFR TKI |
NSCLC patients with acquired EGFR TKI resistance | AstraZeneca |
80 or 160 mg/day for a median of 260 and 171 days, respectively |
ORR: 70% | [241] |
| 2018 | Lorlatinib (lorbrena®) | ATP-competitive small molecule inhibitor of TKI | ALK-positive NSCLC | Pfizer | 100 mg once daily | ROS1‑Positive NSCLC: ORR: 36.2% (95%CI 22.7–51.5), intracranial ORR: 56.0% (95%CI 34.9–75.6), PFS: 9.9 (95%CI 5.5, 21.0) | [243] |
| 2020 | Ramucirumab plus erlotinib | Anti-VEGFR2 agent | NSCLC with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) mutations | Eli Lilly | 10 mg/kg every 2 weeks | ORR: 76%, PFS: 19.4 months | [252] |
| 2020 | Pralsetinib (GAVRETO™) | RET inhibitor | Patients with RET fusion-positive metastatic NSCLC | Blueprint Medicines Corporation | 400 mg orally once daily | [253] | |
| 2020 | Nivolumab ( OPDIVO) plus ipilimumab ( YERVOY) | Anti-PD1, Anti-CTLA-4 | NSCLC with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations | Bristol-Myers Squibb Co | 360 mg nivolumab every 3 weeks with ipilimumab 1 mg/kg every 6 weeks | ORR: 38% (95% CI 33, 43) PFS: 6.8 months (95% CI 5.6, 7.7) OS: 14.1 months (95% CI 13.2, 16.2) | [248] |
| 2020 | brigatinib (ALUNBRIG) | Tyrosine kinase inhibitor | Anaplastic lymphoma kinase (ALK)-positive metastatic NSCLC | ARIAD Pharmaceuticals Inc | 90 mg orally once daily for the first 7 days; then increase to 180 mg orally once daily. Brigatinib may be taken with or without food | ORR: 74% (95% CI 66, 81) PFS: 24 months (95% CI 18.5, NE) | [254] |
| 2020 | Atezolizumab (TECENTRIQ®) | Anti-PD-L1 | NSCLC with high PD-L1 expression and no EGFR or ALK genomic tumor aberrations | Genentech Inc | 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks, administered intravenously over 60 min | ORR: 38% (95% CI 29, 48), PFS: 8.1 months (95% CI 6.8, 11.0), OS: 20.2 months (95% CI 16.5, NE) | [246] |
| 2020 | Tepotinib (Tepmetko™) | MET TKI | Advanced or recurrent NSCLC with METex14 skipping alterations | Merck | 500 mg once daily | PFS: 9.5–12.2 months | [244, 245] |
| 2020 | Capmatinib ( Tabrecta™) | Oral MET inhibitor | NSCLC with MET exon 14 skipping mutations | Novartis | 400 mg orally twice daily | ORR: 68% (95% CI 48, 84) | [255] |
| 2020 | Selpercatinib (RETEVMO | ATP-competitive, highly selective small-molecule inhibitor of RET kinase | metastatic RET fusion-positive NSCLC | Eli Lilly | 120 mg for patients less than 50 kg, and 160 mg for those 50 kg or greater | ORR: 85% (95% CI 70%, 94%) | [256] |
| 2021 | Sotorasib (LUMAKRAS™) | RAS GTPase family inhibitor | NSCLC KRA mutations | Amgen |
960 mg taken orally once daily (with or without food) |
ORR: 35% DCR: 91% median DOR: 10.9 months PFS: 6.3 months | [35, 257] |
| 2021 | Cemiplimab-rwlc (Libtayo®) | Anti-PD-L1 | NSCLC with high PD-L1 expression (Tumor Proportion Score [TPS] > 50%) and no EGFR, ALK or ROS1 aberrations | Regeneron Pharmaceuticals, Inc | 350 mg every 3 weeks, intravenously over 30 min | ORR: 37% (95% CI 32, 42) PFS: 6.2 months (4.5, 8.3) OS: 22.1 months | [247] |
| 2021 | Amivantamab-vmjw (Rybrevant®) | Monoclonal antibody directed against EGFR and MET | NSCLC with EGFR exon 20 insertions | Janssen Biotech | 1050 mg (if bodyweight was < 80 kg) or 1400 mg (if bodyweight was ≥ 80 kg) once weekly for 4 weeks | ORR: 40% (95% CI 29–51%), DOR: 11.1 months (95% CI 6.9 to not estimable), PFS: 8.3 month OS: 22.8 months | [143, 258] |
NSCLC non-small cell lung cancer, EGFR epidermal growth factor receptor, TKI tyrosine kinase inhibitor, RET rearranged during transfection, MET mesenchymal-epithelial transition factor, ORR objective response rate, DoR duration of response, PFS progression-free survival, OS overall survival