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Table 1 Landmark clinical trials in the development of small-molecule EGFR TKIs

From: Clinical development of targeted and immune based anti-cancer therapies

Drug Name

Clinical Trial ID

Trial Name

Population

Comparator

Year

Sponsor

Phase

N

Median OS (months)

Median PFS (months)

Small-molecule EGFR TKIs

 1st Generation EGFR TKI

  Gefitinib (Iressa®/ZD1839)

   Gefitinib (250 mg/d)

NCT00322452

IPASS

NSCLC

Chemotherapy

2006–2010

AstraZeneca

III

1329

18.6 vs 17.3

5.7 vs 5.8/24.9 vs 6.7%

   Gefitinib (250 mg/d)

NCT01203917

IFUM

NSCLC (EGFR+)

None

2010–2013

AstraZeneca

IV

1060

19.2

7.0

  Erlotinib (Tarceva®)

   Erlotinib (150 mg/d)

NCT00036647

BR.21

NSCLC

Placebo

2001–2004

OSI Pharmaceuticals

III

731

6.7 vs 4.7

2.2 vs 1.8

   Erlotinib (150 mg/d)

NCT00556712

SATURN

NSCLC

Placebo

2010–2013

Hoffmann-La Roche

Obs

289

12.4 vs 11.0

12.3 vs 11.1

   Erlotinib (150 mg/d)

NCT01328951

IUNO

NSCLC

Placebo

2011–2016

Hoffmann-La Roche

III

643

9.7 vs 9.5

3.0 vs 2.8

   Erlotinib (100 mg/d) + Gemcitabine (1000 mg/m2/w)

NCT02694536

 

Pancreatic cancer

None

2006–2009

Hoffmann-La Roche

III

80

7.5

4.9

  Lapatinib (Tykerb®)

   Lapatinib (1250 mg/d) + capecitabine (2000 mg/m2)

NCT00078572

 

Breast (HER2+)

Capecitabine

2004–2006

GSK

III

408

17.3 vs 14.9

7.2 vs 4.3

   Lapatinib (1500 mg/d) + letrozole (2.5 mg/d)

NCT00073528

 

Breast (ER/PR +)

Letrozole

2003–2018

Norvatis

III

1285

33.3 vs 32.3

8.1 vs 3.0

   Lapatinib (1500 mg/d)

NCT00374322

TEACH

Breast (HER2+)

Placebo

2006–2013

GSK

III

3166

7.3 vs 8.0%

13.3 vs 15.8%

 2nd Generation EGFR TKI

  Afatinib (BIBW 2992/Gilotrif®)

   Afatinib (50 mg/d)

NCT00525148

LUX-Lung 2

NSCLC

None

2007–2015

Boehringer Ingelheim

II

129

26.8

10.2

   Afatinib (40 mg/d)

NCT00949650

LUX-Lung 3

NSCLC, Adenocarcinoma

Pemetrexed + cisplatin

2009–2017

Boehringer Ingelheim

III

345

28.2 vs 28.2

11.2 vs 6.9

   Afatinib (40 mg/d)

NCT01121393

LUX-Lung 6

NSCLC, Adenocarcinoma

Gemcitabine + cisplatin

2010–2017

Boehringer Ingelheim

III

364

23.1 vs 23.5

11.0 vs 5.6

   Afatinib (40-50 mg/d)

NCT01523587

LUX-Lung 8

NSCLC

Erlotinib

2012–2017

Boehringer Ingelheim

III

795

NR

2.4 vs 1.9

   Afatinib (40 mg/d) + vinorelbine (25 mg/m2)

NCT01125566

LUX-Breast 1

Breast (HER2+)

Trastuzumab + vinorelbine

2010–2018

Boehringer Ingelheim

III

508

19.6 vs 28.6

5.5 vs 5.6

   Afatinib (40 mg/d)

NCT01271725

LUX-Breast 2

Breast (HER2+)

Afatinib + vinorelbine + paclitaxel

2011–2017

Boehringer Ingelheim

II

74

NR

NR

   Afatinib (40 mg/d)

NCT01441596

LUX-Breast 3

Breast (HER2+)

Investigator’s choice

2011–2015

Boehringer Ingelheim

II

121

13.3 vs 12.0

2.7 vs 4.2

  Dacomitinib (Vizimpro®)

   Dacomitinib (45 mg/d)

NCT01774721

ARCHER 1050

NSCLC (EGFR mutant)

Gefitinib

2013–2016

SFJ Pharmaceuticals

III

440

16.9 vs 11.9

14.7 vs 9.2

Vandetanib (Caprelsa®)

   Vandetanib (300 mg/d)

NCT00410761

ZETA

Thyroid

Placebo

2006–2019

Sanofi

III

437

13.9 vs 16.0%

30.5 vs 19.2

   Vandetanib (300 mg/d)

NCT00409968 NCT00411671 NCT00411632 NCT00410059 NCT00410189

BATTLE Program

NSCLC

Erlotinib, erlotinib + bexarotene, sorafenib

2006–2018

United States Department of Defense

II

255

33.0%

1.8

  Neratinib (Nerlynx®)

   Neratinib (240 mg/d)

NCT00878709

ExteNET

Breast Cancer

Placebo

2009–2020 (active)

Puma Biotechnology, Inc.

III

2840

4.7 vs 8.0 (DFS)

NR

 3rd Generation EGFR TKI

  Osimertinib (Tagrisso®)

   Osimertinib (80 mg/d)

NCT01802632

AURA extension

NSCLC (EGFR-T790 M)

None

2013–2018

AstraZeneca

I/II

201 [603]

NR

9.7

   Osimertinib (80 mg/d)

NCT02094261

AURA 2

NSCLC (EGFR-T790 M)

None

2014–2019

AstraZeneca

II

210

NR

8.6

   Osimertinib (80 mg/d)

NCT02151981

AURA 3

NSCLC

Chemotherapy

2014–2018 (active)

AstraZeneca

III

419

NR

10.1 vs 4.4

  Rociletinib

   Rociletinib (500–750 mg BD)

NCT01526928

 

NSCLC

None

2012–2019

Clovis Oncology, Inc.

I/II

605

 

13.1

  Naquotinib

   Naquotinib (dose NR)

NCT02588261

SOLAR

NSCLC

Erlotinib or gefitinib

2016–2017 (terminated)

Astellas Pharma Inc

III

530

NR

NR