How do I use this list?
The purpose of this resource is to assist you and your doctor if you are considering drug therapies, either through a clinical trial, off-label prescription, or compassionate use.
The tables below include drug therapies corresponding to all mechanisms of action that the Chordoma Foundation's medical and scientific advisors have identified as relevant to chordoma treatment AND that are available to patients through a clinical trial, off-label prescription, or compassionate use. A drug therapy's mechanism of action is the way in which it attacks tumor cells. For example, the mechanism of action of an EGFR inhibitor is to “turn off” the function of the EGFR protein. The EGFR protein is also referred to as the drug's target.
A few important things to remember as you search this list:
- If you have results from molecular testing of your tumor, you and your doctor should take those results into account when considering the options listed below. Your results may make a certain treatment relevant for you, no matter where it is included in this list.
- Similarly, your current situation and individual medical history may indicate or rule out certain therapies.
- Therapies in this list may not be available to every patient. For example, new, experimental therapies are only available through clinical trials, and clinical trials have a limited number of sites. Off-label prescriptions for drugs approved for other tumor types may not be paid for by insurance providers or allowed by national health systems. Additionally, compassionate use programs may not be available or the programs may have qualifications such as country of residence or income level.
- There are clinical trials in this list that are not specifically enrolling chordoma patients but are open to patients with advanced solid tumors. We cannot guarantee that these trials or all trial sites will accept chordoma patients. Your doctor can help you contact trial sites to determine if you are eligible.
Recommendations from the Medical Advisory Board
If you are considering drug therapies, the Chordoma Foundation Medical Advisory Board recommends that you consult with a chordoma-experienced medical oncologist about drug therapies that may be right for you based on your individual tumor and medical situation, taking into consideration the full range of options and associated evidence, including those presented here in the Chordoma Foundation’s list of drug therapy options.
Therapies with published evidence from a chordoma clinical trial
This table includes all therapies that have published evidence from a prospective Phase 1 or Phase 2 clinical trial that included chordoma patients. If a drug is meant for a specific subtype of chordoma or a certain mutation is required for clinical trial eligibility, those details are included in brackets along with the drug or trial.
Inclusion on this list does not mean that the results of the clinical trial were positive or that the therapy is effective for treating chordoma. Please keep in mind that this information is intended to be one of several things you and your doctor can consider when deciding what is best for your individual situation.
Links to the published evidence for each therapy are included in the table below so you and your doctor can easily access it. If you need help with any of the information below, please get in touch with a Patient Navigator.
|
DRUG NAME |
TARGET |
TYPE OF THERAPY |
AVAILABILITY |
PUBLISHED TRIAL RESULTS |
|---|---|---|---|---|
|
pemetrexed (Alimta®) |
Antifolate |
Chemotherapy |
Off-label |
PubMed, 2023 |
|
lapatinib (Tykerb®) |
EGFR, HER2 |
Targeted therapy |
Off-label |
PubMed, 2013 |
|
tazemetostat (Tazverik®) [for INI1/SMARCB1-negative, poorly differentiated] |
EZH2 |
Targeted therapy |
Clinical trial: NCT05407441 [for INI1/SMARCB1-negative, poorly differentiated; pediatric and young adult only] |
Conference abstract, 2018 |
|
pembrolizumab (Keytruda®) |
PD-1 |
Immune checkpoint inhibitor |
Off-label |
PubMed, 2023 |
|
durvalumab (Imfinzi®) + tremelimumab (Imjudo®) |
PD-L1 + CTLA-4 |
Immune checkpoint inhibitors |
Off-label |
PubMed, 2022 |
|
imatinib (Gleevec®) |
PDGFR, c-KIT, BCR-ABL |
Targeted therapy |
Off-label |
PubMed, 2012 |
|
nilotinib (Tasigna®) + radiation |
PDGFR, c-KIT, BCR-ABL |
Targeted therapy |
Off-label |
PubMed, 2018 |
|
sorafenib (Nexavar®) |
PDGFR, VEGFR, RAF/MEK/ERK |
Targeted therapy |
Clinical trial: NCT02693535 |
PubMed, 2015 |
|
sunitinib (Sutent®) |
PDGFR, VEGFR, c-KIT |
Targeted therapy |
PubMed, 2009 |
|
|
imatinib (Gleevec®) + cyclophosphamide (Cytoxan®) |
PDGFR, c-KIT, BCR-ABL (imatinib) + DNA replication (cyclophosphamide) |
Targeted therapy + chemotherapy |
PubMed, 2013 |
|
|
imatinib (Gleevec®) + everolimus (Afinitor®) |
PDGFR, c-KIT, BCR-ABL (imatinib) + mTOR (everolimus) |
Targeted therapies |
PubMed, 2018 |
|
|
dasatinib (Sprycel®) |
PDGFR, c-KIT |
Targeted therapy |
PubMed, 2016 |
|
|
adAPT-001 |
TGF-beta |
Oncolytic adenovirus |
PubMed, 2023 |
|
|
rivoceranib/apatinib (Aitan®) |
VEGFR |
Targeted therapy |
PubMed, 2020 |
|
|
regorafenib (Stivarga®) |
VEGFR, c-KIT, PDGFR |
Targeted therapy |
Clinical trial: NCT02693535 |
PubMed, 2023 |
Therapies for which chordoma clinical trials have not yet been completed
These tables include therapies that have strong rationale for their use in chordoma and:
Are currently being studied in a prospective chordoma-specific clinical trial, AND/OR
Have published clinical (in chordoma patients) evidence not from a clinical trial, OR
Have published preclinical (in cell lines and/or mouse models) evidence in chordoma.
Each therapy in this category has been assigned to Priority Level 1 or Priority Level 2 by our medical and scientific advisors, as defined below. If a drug is meant for a specific subtype of chordoma or a certain mutation is required for clinical trial eligibility, those details are included in brackets along with the drug or trial.
Click on the Level 1 and Level 2 tabs below to see the full list of therapies in each level.
Therapies with strong scientific rationale for the mechanism of action or target
The targets in this table and their corresponding therapies have been nominated by our medical and scientific advisors for further study in chordoma. For each target, the table below indicates whether a corresponding therapy is available off-label or through a clinical trial. In some cases, preclinical data may not be published or publicly available yet for a specific therapy.
If a drug is meant for a specific subtype of chordoma or a certain mutation is required for clinical trial eligibility, those details are included in brackets along with the drug or trial.
|
TARGET |
DRUGS AVAILABLE OFF-LABEL |
DRUGS AVAILABLE THROUGH CLINICAL TRIALS |
LINKS TO OR SUMMARIES OF EXISTING EVIDENCE |
|---|---|---|---|
|
ATR |
N/A |
Summary of data coming soon |
|
|
CDK4/6 |
abemaciclib (Verzenio®) |
PubMed |
|
|
CDK9 |
N/A |
Conference abstract [KB-0742] |
|
|
DNA replication |
ifosfamide (Ifex®) |
N/A |
Ifosfamide is often given in combination with other chemotherapy drugs for treatment of poorly differentiated chordoma, and there are case reports of such combinations. |
|
DNA replication + thymidylate synthase (TS) |
temozolomide (Temodar®) + pemetrexed (Alimta®) |
Both drugs have been individually nominated by our MAB for further study in chordoma and the combination has been tested in a Phase 2 trial of patients with other tumor types. |
|
|
EGFR |
gefitinib (Iressa®) |
EGFR is frequently activated in chordoma, various EGFR inhibitors have demonstrated efficacy in preclinical models of chordoma, and there have been several anecdotal responses to EGFR inhibitors. |
|
|
PRMT5 |
N/A |
The MTAP gene is often co-deleted in chordoma tumors along with its chromosomal neighbor CDKN2A. MTAP loss leads to partial inhibition of PRMT5, sensitizing tumor cells to further inhibition of PRMT5 with targeted drugs. Find more information on MTAP deletion here. |
|
|
PARP |
olaparib (Lynparza®) |
Chordoma Foundation Figshare data [olaparib] |
|
|
PARP + DNA replication |
olaparib (Lynparza®) + temozolomide (Temodar®) |
Chordoma Foundation Figshare data [olaparib + temozolomide] |
|
|
PD-1/PD-L1 |
atezolizumab (Tecentriq®) |
atezolizumab [for INI1/SMARCB1-negative, poorly differentiated] |
There have been several case series and numerous case reports indicating that some chordoma patients respond to other PD-1 or PD-L1 inhibitors. |
|
PDGFR, VEGFR, c-KIT |
sunitinib (Sutent®) |
PDGFR and VEGFR are frequently activated in chordoma, various PDGRF and VEGFR inhibitors have demonstrated efficacy in preclinical models of chordoma, and there have been several anecdotal responses to PDGRF and VEGFR inhibitors. |
|
|
VEGF |
bevacizumab (Avastin®) |
VEGF is frequently activated in chordoma, various VEGF inhibitors have demonstrated efficacy in preclinical models of chordoma, and there have been several anecdotal responses to VEGF inhibitors. |
The information provided herein is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your or your child’s physician about any questions you have regarding your or your loved one’s medical care. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.