Table 1 The summarized targeted therapy studies in NSCLC

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]