Introduction
Patients and methods
Case selection
Tumor samples
DNA extraction
Next-generation sequencing (NGS)
Immunohistochemistry for HER2/Neu
Results
Characteristics | GBCA (n = 9) | CCA (n = 5) |
---|---|---|
Sex | ||
Male | 2 | 5 |
Female | 7 | 0 |
Age (years) | ||
20–39 | 0 | 2 |
40–59 | 3 | 1 |
≥60 | 6 | 2 |
Ethnicity | ||
Asian | 1 | 0 |
White | 8 | 5 |
Tumor differentiation | ||
Poor | 1 | 1 |
Moderate | 8 | 4 |
Pt # | Sites of disease | Prior therapy | HER2/neu test | HER2/neu therapy | Concurrent therapy | Duration of therapy (weeks) | Overall survival (weeks) | Best response |
---|---|---|---|---|---|---|---|---|
1 | Bone, liver | Nil | IHC 3+ | Trastuzumab | Gemcitabine, cisplatin | 7 | 20 | SD |
2 | Peritoneum, lung, liver | Gemcitabine + cisplatin, FOLFIRI + erbitux | Mutation (NGS) V777L | Lapatinib | Sirolimus | 15 | 19 | MR |
3 | Retroperitoneal LN, liver | Nil | FISH amplification | Trastuzumab | Nil | 38 | 113 | CR |
4 | Liver | Gemcitabine + cisplatin, capecitabine, FOLFOX | ERBB2 NGS amplification | Trastuzumab | Gemcitabine + irinotecan | 40 | 62 | PR |
5 | Liver, LN | Gemcitabine + cisplatin | ERBB2 NGS amplification | Trastuzumab | FOLFOX capecitabine | 92 | 92 | PR |
6 | Sternum, pleura, lung | Gemcitabine, capecitabine | AMPLIFIED (FISH) | Trastuzumab | 168 | 178 | PR | |
7 | Retroperitoneal LN, celiac LN | Nil | AMPLIFIED (FISH) | Trastuzumab | Gemcitabine + cisplatin | 22+ | 22+ | PR |
8 | Retroperitoneal LN, supraclavicular LN | Gemcitabine + capecitabine, gemcitabine + cisplatin, pazopanib, dovitinib | ERBB2 NGS amplification | Trastuzumab + pertuzumab | Nil | 8+ | 8+ | SD |
9 | Lungs, brain | Gemcitabine + cisplatin radiation | IHC 3+ | Trastuzumab | Paclitaxel capecitabine | 72 | 96+ | PR |
Pt # | Sites of disease | Prior therapy | HER2/neu test | HER2/neu therapy | Concurrent therapy | Duration of therapy | Overall survival | Best response |
---|---|---|---|---|---|---|---|---|
1 | Liver, mediastinum, Lung | Gemcitabine folfirinox | Mutation (NGS) V777L | Trastuzumab | Gemcitabine, docetaxel | 19 | 29 | PD |
2 | Liver, peritoneum, lung | Gemcitabine + cisplatin | ERBB2 amp NGS | Trastuzumab | FOLFOX | 14 | 25 | PD |
3 | Mediastinum | Gemcitabine + cisplatin, FOLFIRI, GTX | ERBB2 NGS S310F | Trastuzumab | FOLFOX | 7 | 7 | PD |
4 | Liver, lung | Nil | AMPLIFIED (FISH) | Trastuzumab | 6 | 8 | PD | |
5 | Lung, liver, bones | Gemcitabine + cisplatin | AMPLIFIED (FISH) | Trastuzumab | 10 | 12 | PD |
Cancer type | HER2/neu status | Associated mutations | Best response | Agent | PFS (weeks) | OS (weeks) |
---|---|---|---|---|---|---|
Cholangioca | Mutation (V777L) | FGFR3, TP53 | SD | Trastuzumab | 19 | 29 |
Cholangioca | Amplification | BAP1, CDKN2A, KDM6A, PBRM1, SETD2 | PD | Trastuzumab | 14 | 25 |
Cholangioca | Mutation (S310F) | KRAS, MYC, TP53, EZH2, MSH6 | PD | Trastuzumab | 7 | 7 |
Cholangioca | Amplification | PD | Trastuzumab | 6 | 8 | |
Cholangioca | Amplification | PD | Trastuzumab | 10 | 12 | |
Gallbladder cancer | Amplification | PIK3CA, CDKN2A/B, TP53, ZNF703 | MR | Lapatinib | 15 | 19 |
Gallbladder cancer | Amplification | TP53 | PR | Trastuzumab | >92 | >92 |
Gallbladder cancer | Amplification | NRAS, PIK3CA, RB1,PTEN, TP53 | PR | Trastuzumab | >40 | >62 |
Gallbladder cancer | Amplification | PR | Trastuzumab | 168 | 178 | |
Gallbladder cancer | Amplification | PR | Trastuzumab | 38 | 113 | |
Gallbladder cancer | Amplification | FGFR3-TACC3 fusion, TP53, CCNE1, MCL1, MYC | SD | Trastuzumab + pertuzumab | +8 | +8 |