Table 2 Foundation ONE reports of CBL alterations with EGFR, MET, or KRAS alterations and patient treatment outcome.

From: Differential responsiveness of MET inhibition in non-small-cell lung cancer with altered CBL

Patient

Tumor type

CBL mutation

EGFR/MET/KRAS mutation

Chemo/Clinical Trial

Outcome

1

Lung AD

H37_H38insHH

EGFR E746_A750del, T790M

Erlotinib

Was effective for a time but progressive disease

AP26113

1. Interval progression of disease with interval increase in the size of the left lung mass, hepatic metastases, also as metastases and left adrenal metastatic disease.

2. Interval development of right-sided pulmonary static disease.

2

Lung AD

A848T

EGFR E746_A750del, amplification

Carboplatin

Unknown. Tolerated Well

Paclitaxel

Unknown. Tolerated Well

Erlotinib

Good response but discontinued due to poor performance status

3

Lung AD

T810S, amplification

EGFR R429S

Carboplatin

1. No new suspicious pulmonary nodules or masses.

2. Stable upper mediastinal right paratracheal soft tissue mass at the site of prior resection.

Paclitaxel

1. No new suspicious pulmonary nodules or masses.

2. Stable upper mediastinal right paratracheal soft tissue mass at the site of prior resection.

4

NSCLC (NOS)

S80G

 

Carboplatin

Unknown

Gemcitabine

Unknown

5

Lung AD

A848T, E886K

EGFR R1068*, P518L; KRAS G10R, K169N

Carboplatin

1. No significant interval change in the large necrotic right anterior mediastinal mass with extension into the right hilum and right chest wall and sternal/pericardial/SVC invasion.

2. Mild interval improvement in number of pulmonary nodules, specifically in the right upper lobe.

3. Stable retroperitoneal lymphadenopathy.

4. Nonspecific sclerotic focus in vertebral body of T3.

Paclitaxel

1. No significant interval change in the large necrotic right anterior mediastinal mass with extension into the right hilum and right chest wall and sternal/pericardial/SVC invasion.

2. Mild interval improvement in number of pulmonary nodules, specifically in the right upper lobe.

3. Stable retroperitoneal lymphadenopathy. 4. Nonspecific sclerotic focus in vertebral body of T3.

6

Lung AD

E366*

 

CALGB 30303, Phase II IRB 13724 A trial of Docetaxel and Cisplatin

Unknown

Carboplatin

Marked improvement of disease.

7

Lung AD

R420Q

KRAS G12C

No Chemotherapy/Trial

 

8

NSCLC (NOS)

K54E

 

Carboplatin

1. Good response.

2. Interval decrease in size of left upper lobe mass and left hilar/subsegmental lymph node.

3. Left upper lobe mass is now mostly cavitary.

Paclitaxel

1. Good response.

2. Interval decrease in size of left upper lobe mass and left hilar/subsegmental lymph node.

3. Left upper lobe mass is now mostly cavitary.

9

NSCLC (NOS)

A757T

KRAS amplification, G12V

Cisplatin

Clinically no evidence of disease

Docetaxel

Clinically no evidence of disease

Carboplatin

Response in some areas, but progression in right kidney (mixed response?)

Gemcitabine

Response in some areas, but progression in right kidney (mixed response?)

10

Lung AD

Amplification

EGFR L858R

Carboplatin

1. No evidence of acute pulmonary embolus.

2. New geographic areas of groundglass opacities in the right lung.

3. Differential diagnosis includes drug toxicity, atypical infection, and hemorrhage.

4. Stable left lingular mass, sclerotic osseous foci, and metastatic hepatic lesions.

Paclitaxel

1. No evidence of acute pulmonary embolus.

2. New geographic areas of groundglass opacities in the right lung.

3. Differential diagnosis includes drug toxicity, atypical infection, and hemorrhage.

4. Stable left lingular mass, sclerotic osseous foci, and metastatic hepatic lesions.

Erlotinib

Good response but discontinued due to poor performance status

  1. AD: adenocarcinoma; NOS: not otherwise specified.