Abstract 507P
Background
Central nervous system (CNS) metastases rarely occur in colorectal cancer (CRC) patients (1-4%). ERBB2 amplification is detected in 5% of RAS WT metastatic CRC and has been recognized as a therapeutic target for trastuzumab in combination with lapatinib or pertuzumab. We recently reported a high rate of CNS recurrences (19%) among 32 HER2-positive mCRC treated with trastuzumab and lapatinib. Here we describe the prevalence, timing of onset, and management of CNS recurrences in the largest cohort of CRC treated with anti-HER2 therapies.
Methods
Consecutive patients with HER2-positive mCRC by immunohistochemistry and in-situ hybridization, treated with both anti-HER2 regimens within the multi-center HERACLES clinical program and per institutional protocols at Niguarda Cancer Center were included in the analysis.
Results
Between August 2012 and April 2020, 92 patients have been treated with an anti-HER2 regimen: 42 received trastuzumab and lapatinib, 31 pertuzumab and T-DM1 and 19 other treatments in clinical trials. Progression in CNS was clinically evident in 10/92 (11%), with 2 pre-existing and stable after SRS, 5 documented under and 3 after anti-HER2 treatment (table). In 1 patient who underwent neurosurgery to remove metastasis, maintenance of HER2-positivity in the cerebellum was demonstrated. Table: 507P
| Patient | Anti-HER2 Treatment | ORR to anti-HER2 treatment | Brain PFS* (months) | Brain metastases treatment | OS (months) |
| 1 | T+L | SD | 59.8 | Surgery | 77.9 |
| 2 | T+L | PR | 51.0 | None | 51.3 |
| 3 | T+L | SD | 32.9 | - | 36.5 |
| 4 | T+L | PR | 57.8 | None | 62.6 |
| 5 | T+L | PD | 33.9 | SRS | 36.8 |
| 6 | T+L | SD | 13.7 | SRS | 21.4 |
| 7 | T+L | PD | 26.3 | SRS | 29.0 |
| 8 | P+T-D | PD | 38.7 | SRS | 45.7 |
| 9 | P+T-D--> O | SD; PD | 18.6 | None | 19.8 |
| 10 | O--> T+L | PR; PD | 84.9 | Surgery | 85.4+ |
*=from diagnosis of stage IV ORR=Objective Response Rate; PFS=Progression Free Survival; OS=Overall Survival; PD=Progressive Disease; PR=Partial Response; SD=Stable Disease; T=trastuzumab; L=lapatinib; P=pertuzumab; T-D=T-DM1; O=other anti-Her2 in clinical trial; SRS=Stereotactic radiosurgery; +=ongoing.
Conclusions
Present data indicate a high prevalence of CNS recurrences in HER2-positive mCRC, suggesting that the CNS may represent a sanctuary of relapse and that brain imaging for staging and tumor assessment is warranted.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Authors are supported by grants from: Associazione Italiana Ricerca Cancro grant AIRC 5 x mille and Fondazione Oncologia Niguarda.
Disclosure
A. Sartore-Bianchi: Advisory/Consultancy: Amgen; Advisory/Consultancy: Bayer; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Servier. A. Amatu: Advisory/Consultancy: Amgen; Advisory/Consultancy: Roche; Advisory/Consultancy: Bayer. A. Ardizzoni: Research grant/Funding (self): BMS; Honoraria (self): MSD; Honoraria (self): Eli-Lilly; Honoraria (self): Boehringer; Honoraria (self): Pfizer; Research grant/Funding (self): Celgene; Research grant/Funding (self): Roche. F. Ciardiello: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Amgen; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Bayer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Celgene; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Research grant/Funding (institution): Merck; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Research grant/Funding (institution): Roche; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Servier; Research grant/Funding (self): Ipsen; Research grant/Funding (institution): Symphogen; Research grant/Funding (institution): Array; Leadership role, past president: ESMO; Leadership role, president: AIOT. V. Zagonel: Advisory/Consultancy: BMS; Advisory/Consultancy: Merck; Speaker Bureau/Expert testimony: Astrazeneca; Speaker Bureau/Expert testimony: Lilly; Honoraria (self): Bayer; Honoraria (self): Roche; Honoraria (self): Servier. S. Siena: Advisory/Consultancy: Amgen; Advisory/Consultancy: Bayer; Advisory/Consultancy: BMS; Advisory/Consultancy: CheckmAb; Advisory/Consultancy: Clovis; Advisory/Consultancy: Daiichi-Sankyo; Advisory/Consultancy: Merck; Advisory/Consultancy: Roche; Advisory/Consultancy: Seattle Genetics. All other authors have declared no conflicts of interest.