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Table 1 Panoramic view of clinical trials and retrospective studies with novel drugs for anaplastic thyroid cancer

From: Recent advances in the management of anaplastic thyroid cancer

Pharmacodynamic Property

Tested Drug(s)

First Author

Study Design

ATC patients N°

(out of total)

Prior ATC cohort therapies (%)

ATC Staging (%)

ORR (%)

DCR (%)

Median OS, months

CTX

XRT

Surgery

IVA

IVB

IVC

mTKI

Lenvatinib

Tahara

Phase II

17 (out of 51)

7 (41)

9 (53)

14 (82)

4 (24)

5 (29)

6 (35)

4/17 (24)

16/17 (94)

10.6

Iwasaki

Retrospective

23 (out of 23)

0 (0)

0 (0)

10 (43)

0 (0)

0 (0)

23 (100)

4/23 (17)A

10/23 (44)A

5.5B

Iyer

Retrospective

16 (out of 16)

9 (69)

7 (44)

8 (50)

0 (0)

4 (25)

12 (75)

3/10 (30)

7/10 (70)

3.9

Sorafenib

Savvides

Phase II

20 (out of 20)

20 (100)

18 (90)

18 (90)

0 (0)

0 (0)

20 (100)

2/20 (10)

7/20 (35)

3.9

Ito

Phase II

10 (out of 18)

6 (60)

7 (70)

7 (70)

1 (10)

0 (0)

8 (80)

0/10 (0)

4/10 (40)

5.0

Sunitinib

Ravaud

Phase II

4 (out of 71)

NA

NA

NA

0 (0)

0 (0)

4 (100)

0/4 (0)

1/4 (25)

NA

PP-compounds

CLM3/24/29

-

-

-

-

-

-

-

-

-

-

-

-

Vandetanib

-

-

-

-

-

-

-

-

-

-

-

-

Axitinib

Cohen

Phase II

2 (out of 60)

NA

NA

NA

NA

NA

NA

1/2 (50)

1/2 (50)

NA

Pazopanib

Bible

Phase II

15 (out of 15)

11 (73)

12 (80)

NA

0 (0)

1 (7)

14 (93)

0/15 (0)

0/15 (0)

3.7

Imatinib

Ha

Phase II

11 (out of 11)

9 (82)

7 (64)

0 (0)

5 (45)

6 (55)

2/8 (25)C

6/8 (75)C

NAD

Single target

EGFR

Gefitinib

Pennell

Phase II

5 (out of 27)

3 (60)

NA

NA

0 (0)

5 (100)

0/5 (0)

1/5 (20)

NA

BRAF

Vemurafenib

Hyman

Phase II

7 (out of 122)

7 (100)

6 (86)

NA

NA

NA

NAE

2/7 (28)

2/7 (28)

NA

Dabrafenib +

Trametinib

Subbiah

Phase II

16 (out of 100)

6 (38)

13 (81)

14 (88)

0 (0)

16 (100)

11/16 (69)

14/16 (88)

NA

Iyer

Retrospective

16 (out of 16)

9 (69)

7 (44)

8 (50)

0 (0)

4 (25)

12 (75)

3/6 (50)

5/6 (83)

9.3

mTOR

Everolimus

Lim

Phase II

6 (out of 40)

2 (33)

0 (0)

6 (100)

0/6 (0)

0/6 (0)

NA

Schneider

Phase II

7 (out of 35)

NA

NA

NA

NA

NA

NA

0/7 (0)

0/7 (0)

2.8

Hanna

Phase II

7 (out of 50)

3 (43)

4 (57)

5 (71)

0 (0)

0 (0)

7 (100)

1/7 (14)

3/7 (43)

4.6

PPARγ

TZDs

-

-

-

-

-

-

-

-

-

-

-

-

VEGFR-2

Cyclic amide CLM94

-

-

-

-

-

-

-

-

-

-

-

-

Vascular disrupting

Fosbretabulin

Mooney

Phase II

26 (out of 26)

13 (50)

17 (65)

19 (73)

7 (27)

19 (73)

0/26 (0)

7/26 (27)

4.7

Immunotherapy

(anti PD-1/PD-L1)

Spartalizumab

Capdevila

Phase II

38 (out of 42)F

25 (60)

30 (71)

28 (67)

NA

NA

NA

8/42 (19)

13/42 (31)

5.9

Combination therapy

Sorafenib +

Temsirolimus

Sherman

Phase II

2 (out of 36)

NA

NA

NA

NA

NA

NA

1/2 (50)

1/2 (50)

NA

Efatutazone + Paclitaxel

Smallridge

Phase I

15 (out of 15)G

4 (27)

8 (53)

11 (73)

0 (0)

4 (27)

11 (73)

0/7 (0) vs.

1/6 (17)

4/7 (57) vs.

4/6 (67)

3.3 vs.

4.6

Fosbretabulin +

CP

Sosa

Phase II/III

80 (out of 80)

19 (35)

21 (38)

30 (55)

1 (2)

4 (7)

49 (89)

11/55 (20)

22/55 (40)

5.2

  1. Abbreviations: CTX Chemotherapy (including both traditional and novel drugs); XRT Radiotherapy; ORR Overall Response Rate; DCR Disease Control Rate; OS Overall Survival; mTKI multiple Tirosine-Kinase Inhibitor; PP Pyrazolo [3,4-d]pyrimidine; EGFR Epidermal Growth Factor Receptor; mTOR mammalian Target Of Rapamycin; PPARγ Peroxisome Proliferator-Activated Receptor Gamma; TZDs Thiazolidinediones; VEGFR Vascular Endothelial Growth Factor Receptor; PD-1 Programmed cell Death protein 1; PD-L1 Programmed death-ligand 1; CP Paclitaxel followed by Carboplatin.
  2. NOTES
  3. ABOR was not evaluable in 6 patients
  4. BMedian OS in patients treated surgically vs. patients treated with Lenvatinib only was 8.8 months vs. 4.3 months, respectively
  5. COnly 8 of 11 enrolled patients were evaluable for BOR
  6. DThe rate of 6-month OS was 45%EAt least 6 patients (86%) presented at distance metastasis
  7. FAll data reported refer to the full cohort of patients enrolled, including 4 whose diagnosis of ATC was not histologically confirmed. Most patients had metastatic disease, with lungs and lymph nodes as the most common sites
  8. GORR, DCR and OS refer to Paclitaxel + Efatutazone 0.15 mg vs. Paclitaxel + Efatutazone 0.3 mg cohorts, respectively (two patients adimistered with Efatutazone 0.5 mg only incurred disease progression during the run-in phase)