Colorectal cancer
The EU has approved 21 indications of 11 drugs in colorectal cancer. 10 of them need a biomarker result: MMR/MSI (6) and BRAF (4). 6 tumour-agnostic approvals also apply when the tumour carries the alteration.
Line of therapy
| Drug | Biomarker requirement | Regimen | Setting | Conditions |
|---|---|---|---|---|
| BRAF mutation4 | ||||
Erbitux | V600E | + encorafenib and FOLFOX | 1L metastatic | None |
Braftovi | V600E | + cetuximab and FOLFOX | 1L metastatic | None |
Erbitux | V600E | + encorafenib | 2L metastatic | After prior systemic therapy |
Braftovi | V600E | + cetuximab | 2L metastatic | After prior systemic therapy |
| dMMR / MSI-H6 | ||||
Yervoy | Mismatch repair deficient or microsatellite instability-high | + nivolumab | 1L advanced | None |
Opdivo | Mismatch repair deficient or microsatellite instability-high | + ipilimumab | 1L advanced | None |
Keytruda | Monotherapy | 1L metastatic | None | |
Yervoy | Mismatch repair deficient or microsatellite instability-high | + nivolumab | 2L metastatic | After prior fluoropyrimidine-based combination chemotherapy |
Opdivo | Mismatch repair deficient or microsatellite instability-high | + ipilimumab | 2L metastatic | After prior fluoropyrimidine-based combination chemotherapy |
Keytruda | Monotherapy | 2L advanced | After previous fluoropyrimidine-based combination therapy | |
| RAS negative6 | ||||
Erbitux | RAS wild-type, EGFR-expressing | + FOLFOX | 1L metastatic | None |
Vectibix | Wild-type RAS | + FOLFOX or FOLFIRI | 1L metastatic | None |
Vectibix | Wild-type RAS | + FOLFIRI | 2L metastatic | After first-line fluoropyrimidine-based chemotherapy (excluding irinotecan) |
Erbitux | RAS wild-type, EGFR-expressing | Monotherapy | 3L+ metastatic | Failed oxaliplatin- and irinotecan-based therapy; Intolerant to irinotecan |
Vectibix | Wild-type RAS | Monotherapy | 3L+ metastatic | Failure of fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens |
Erbitux | RAS wild-type, EGFR-expressing | + irinotecan-based chemotherapy | Any line metastatic | None |
| No biomarker required5 | ||||
Zaltrap | None | + irinotecan/5-fluorouracil/folinic acid (FOLFIRI) | 2L metastatic | After oxaliplatin-containing regimen (resistant to or progressed after) |
Cyramza | None | + FOLFIRI (irinotecan, folinic acid, and 5-fluorouracil) | 2L metastatic | After bevacizumab, oxaliplatin and a fluoropyrimidine |
Fruzaqla | None | Monotherapy | 3L+ metastatic | After available standard therapies, including fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapies, anti-VEGF agents, and anti-EGFR agents, and progressed on or intolerant to either trifluridine-tipiracil or regorafenib |
Avastin | None | + fluoropyrimidine-based chemotherapy | Any line metastatic | None |
Stivarga | None | Monotherapy | Any line metastatic | Previously treated with, or are not considered candidates for, available therapies (including fluoropyrimidine-based chemotherapy, an anti-VEGF therapy and an anti-EGFR therapy) |
Tumour-agnostic approvals6
Approved for any solid tumour that carries the alteration, wherever the tumour started.
| Drug | Biomarker requirement | Regimen | Setting | Conditions |
|---|---|---|---|---|
| EpCAM1 | ||||
Korjuny | Monotherapy | 2L | Malignant ascites; not eligible for further systemic anticancer therapy | |
| HER21 | ||||
Enhertuconditional | HER2-positive (IHC 3+) | Monotherapy | 2L advanced | After prior treatment; No satisfactory treatment options |
| NTRK fusion3 | ||||
Rozlytrekconditional | Monotherapy | Any line | No prior NTRK inhibitor; Older than 1 month; disease that is locally advanced, metastatic or where surgical resection is likely to result in severe morbidity; no satisfactory treatment options | |
Vitrakviconditional | Monotherapy | Any line | Locally advanced, metastatic or where surgical resection is likely to result in severe morbidity; no satisfactory treatment options | |
Augtyroconditional | Monotherapy | Any line advanced | Prior NTRK inhibitor, or no prior NTRK inhibitor and treatment options not targeting NTRK provide limited clinical benefit or have been exhausted; Aged 12 years and older | |
| RET fusion1 | ||||
Retsevmo | Monotherapy | Any line advanced | Treatment options not targeting RET provide limited clinical benefit, or have been exhausted; Aged 2 years and older | |
Biomarkers in colorectal cancer
Label wording21
The sentence from section 4.1 of the SmPC that each indication above comes from.
- Pembrolizumab (Keytruda)
first-line treatment of metastatic colorectal cancer;
- Pembrolizumab (Keytruda)
treatment of unresectable or metastatic colorectal cancer after previous fluoropyrimidine-based combination therapy.
- Nivolumab (Opdivo)
first-line treatment of unresectable or metastatic colorectal cancer;
- Nivolumab (Opdivo)
treatment of metastatic colorectal cancer after prior fluoropyrimidine-based combination chemotherapy (see section 5.1).
- Bevacizumab (Avastin)
Bevacizumab in combination with fluoropyrimidine-based chemotherapy is indicated for treatment of adult patients with metastatic carcinoma of the colon or rectum.
- Fruquintinib (Fruzaqla)
FRUZAQLA as monotherapy is indicated for the treatment of adult patients with metastatic colorectal cancer (mCRC) who have been previously treated with available standard therapies, including fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapies, anti-VEGF agents, and anti-EGFR agents, and who have progressed on or are intolerant to treatment with either trifluridine-tipiracil or regorafenib.
- Encorafenib (Braftovi)
Encorafenib in combination with cetuximab is indicated for the treatment of adult patients with metastatic colorectal cancer with a BRAF V600E mutation, who have received prior systemic therapy.
- Encorafenib (Braftovi)
Encorafenib in combination with cetuximab and FOLFOX is indicated for the first line treatment of adult patients with metastatic colorectal cancer with a BRAF V600E mutation.
- Cetuximab (Erbitux)
Erbitux is indicated for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing, RAS wild-type metastatic colorectal cancer • in combination with irinotecan-based chemotherapy,
- Cetuximab (Erbitux)
Erbitux is indicated for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing, RAS wild-type metastatic colorectal cancer • in combination with irinotecan-based chemotherapy, • in first-line in combination with FOLFOX,
- Cetuximab (Erbitux)
Erbitux is indicated for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing, RAS wild-type metastatic colorectal cancer • in combination with irinotecan-based chemotherapy, • in first-line in combination with FOLFOX, • as a single agent in patients who have failed oxaliplatin- and irinotecan-based therapy and who are intolerant to irinotecan.
- Cetuximab (Erbitux)
• in combination with encorafenib and FOLFOX for the first line treatment.
- Cetuximab (Erbitux)
• in combination with encorafenib in patients who have received prior systemic therapy.
- Ipilimumab (Yervoy)
YERVOY in combination with nivolumab is indicated for the treatment of adult patients with mismatch repair deficient or microsatellite instability-high colorectal cancer in the following settings: - first-line treatment of unresectable or metastatic colorectal cancer;
- Ipilimumab (Yervoy)
YERVOY in combination with nivolumab is indicated for the treatment of adult patients with mismatch repair deficient or microsatellite instability-high colorectal cancer in the following settings: - first-line treatment of unresectable or metastatic colorectal cancer; - treatment of metastatic colorectal cancer after prior fluoropyrimidine-based combination chemotherapy (see section 5.1).
- Regorafenib (Stivarga)
- metastatic colorectal cancer (CRC) who have been previously treated with, or are not considered candidates for, available therapies. These include fluoropyrimidine-based chemotherapy, an anti-VEGF therapy and an anti-EGFR therapy (see section 5.1)
- Ramucirumab (Cyramza)
Cyramza, in combination with FOLFIRI (irinotecan, folinic acid, and 5-fluorouracil), is indicated for the treatment of adult patients with metastatic colorectal cancer (mCRC) with disease progression on or after prior therapy with bevacizumab, oxaliplatin and a fluoropyrimidine.
- Panitumumab (Vectibix)
in first-line in combination with FOLFOX or FOLFIRI.
- Panitumumab (Vectibix)
in second-line in combination with FOLFIRI for patients who have received first-line fluoropyrimidine-based chemotherapy (excluding irinotecan).
- Panitumumab (Vectibix)
as monotherapy after failure of fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.
- Aflibercept (Zaltrap)
ZALTRAP in combination with irinotecan/5-fluorouracil/folinic acid (FOLFIRI) chemotherapy is indicated in adults with metastatic colorectal cancer (MCRC) that is resistant to or has progressed after an oxaliplatin-containing regimen.