Table 3 Cell cycle pathway alterations found in study patients by IHC and next-generation sequencing

From: Phase II trial of palbociclib in patients with metastatic urothelial cancer after failure of first-line chemotherapy

IDa

RB IHC

p16 IHC

Gene

Alteration

Predicted sensitivity to palbociclib

PFS4

1

3+ in 20%

2+ in 40%

1+ in 30%

0+ in 10%

3+ staining in 30%

CDKN1A

CDKN1A

Asp28Gly

Pro4Leu

Resistant

Resistant

No

2

3+ in 10%

2+ in 20%

1+ in 20%

0+ in 50%

No staining

CDKN2B

Shallow deletion

Sensitive

No

3

3+ in 30%

2+ in 40%

1+ in 30%

No staining

Nonea

  

No

4

2+ in 30%

1+ in 40%

0+ in 30%

No staining

CDKN2B

Shallow deletion

Sensitive

No

5

2+ in 70%

1+ in 20%

0+ in 10%

No staining

CDKN2B

Deep deletion

Sensitive

No

6

2+ in 10%

1+ in 80%

0+ in 10%

No staining

Nonea

  

No

7

3+ in 30%

2+ in 40%

1+ in 30%

No staining

E2F3

Gain

Resistant

No

8

2+ in 30%

1+ in 70%

No staining

CCNE1

CDKN1A

CDKN1A

Gain

Asp28Gly

Pro4Leu

Resistant

Resistant

Resistant

Yes

9

2+ in 30%

1+ in 60%

0+ in 10%

1 + staining in 90%

RB1

Amplification

N/A

No

10

2+ in 50%

1+ in 30%

0+ in 20%

No staining

CDKN1A

FS111

Resistant

Yes

11

3+ in 20%

2+ in 20%

1+ in 10%

No staining

E2F3

Asp389Asn

Resistant

No

12

3+ in 10%

2+ in 30%

1+ in 30%

0+ in 30%

No staining

Unknowna

  

No

  1. aPatients 3 and 6 did not have any cell cycle alterations, patient 12 did not have adequate tissue for sequencing