Nivolumab (29) – Opdivo®

Colorectal cancer with MSI-H or dMMR, first-line treatment, in combination with ipilimumab

Characteristics

Start date 15.06.2025 – Marketing authorisation: 19.12.2024
Resolution 18.12.2025
INN Nivolumab
Brand name Opdivo®
Pharm. company Bristol-Myers Squibb GmbH & Co. KGaA
G-BA Procedure ID D-1189
ATC code L01FF01 PD-1/PDL-1 inhibitors (L01FF)
ICD-10 codes (AIS) C18.0Malignant neoplasm of ileocecal valve, C18.1Malignant neoplasm of appendix, C18.2Malignant neoplasm of ascending colon, C18.3Malignant neoplasm of hepatic flexure, C18.4Malignant neoplasm of transverse colon, C18.5Malignant neoplasm of splenic flexure, C18.6Malignant neoplasm of descending colon, C18.7Malignant neoplasm of sigmoid colon, C18.8Malignant neoplasm of overlapping sites of colon, C18.9Malignant neoplasm of large intestine NOS, C19Malignant neoplasm of rectosigmoid junction, C20Malignant neoplasm of rectum
Alpha-ID codes (AIS) I104488Malignant neoplasm of the rectosigmoid junction, I115345Carcinoma of the colon and sigmoid colon, I18119Malignant neoplasm of the rectum, I25671Malignant neoplasm of the flexura coli sinistra, I29955Malignant neoplasm of the colon, I29956Malignant neoplasm of the caecum, I29957Malignant neoplasm of the vermiform appendix, I29959Malignant neoplasm of the ascending colon, I29964Malignant neoplasm of the flexura coli dextra, I29966Malignant neoplasm of the transverse colon, I29971Malignant neoplasm of the descending colon, I29972Malignant neoplasm of the sigmoid colon
Therapeutic area Oncological diseases
Reason for procedure New therapeutic indication

Therapeutic indication of the resolution

Opdivo is indicated in combination with ipilimumab for the treatment of colorectal cancer with mismatch repair deficiency or high microsatellite instability in adults in the following cases:

– First-line treatment of unresectable or metastatic colorectal cancer

Subpopulation Indication Comparator
Erwachsene mit nicht resezierbarem oder metastasiertem Kolorektalkarzinom mit Mismatch-Reparatur-Defizienz oder hoher Mikrosatelliteninstabilität; Erstlinientherapie

Studies and Results

  • Clinical trials
    • The CA209-8HW trial is an open-label, three-arm, randomised controlled trial that began in 2019 and is currently ongoing, comparing nivolumab in combination with nivolumab versus nivolumab versus chemotherapy as determined by the treating physician.
    • The KEYNOTE 177 trial is a completed, open-label, randomised controlled trial comparing pembrolizumab with chemotherapy as determined by the treating physician.

Adults with unresectable or metastatic colorectal cancer with mismatch repair deficiency or high microsatellite instability; first-line treatment

  • The additional benefit is not proven.
  • Consequently, there are no data available in the overall review that would allow an assessment of the additional benefit.
  • Overall review
    • A key prerequisite for including studies in an adjusted indirect comparison via a bridge comparator is the similarity of the studies. In this regard, there are significant differences between the CA209-8HW and KEYNOTE 177 studies with respect to the testing of MSI-H and dMMR status.
    • Consequently, against the backdrop of a result that is only just statistically significant, the data on overall survival are not suitable for drawing conclusions regarding additional benefit.
    • Given the central importance of overall survival data in this therapeutic indication and for demonstrating additional benefit through indirect comparisons, and taking into account the limited data available on patient-relevant endpoints, the adjusted indirect comparison is, on the whole, assessed as unsuitable for drawing conclusions regarding additional benefit.

Courtesy translation only, please refer to the German original.

Associated procedures

Nivolumab (33) Opdivo® Bristol-Myers Squibb GmbH & Co. KGaA Oncological diseases Urothelial carcinoma, PD-L1 expression ≥ 1 %, adjuvant therapy 680–830 100% Hint for considerable additional benefit
Nivolumab (32) Opdivo® Bristol-Myers Squibb GmbH & Co. KGaA Oncological diseases Cancer of the oesophagus or gastro-oesophageal junction, in previously treated patients, as adjuvant therapy 580–910 100% Hint for minor additional benefit
Nivolumab (29) Opdivo® Bristol-Myers Squibb GmbH & Co. KGaA Oncological diseases Colorectal cancer with MSI-H or dMMR, first-line treatment, in combination with ipilimumab 560–1,800 100% additional benefit not proven
Nivolumab (31) Opdivo® Bristol-Myers Squibb GmbH & Co. KGaA Oncological diseases Non-small cell lung cancer, PD-L1 expression ≥ 1 per cent, neoadjuvant and adjuvant therapy, monotherapy or in combination with platinum-based chemotherapy 3,240–3,680 100% additional benefit not proven
Nivolumab (30) Opdivo® Bristol-Myers Squibb GmbH & Co. KGaA Oncological diseases Unresectable or advanced hepatocellular carcinoma, first-line treatment, in combination with ipilimumab 1,900–5,470 100% additional benefit not proven
Nivolumab (28) Opdivo® Bristol-Myers Squibb GmbH & Co. KGaA Oncological diseases Urothelial carcinoma, first-line, combination with cisplatin and gemcitabine 435–617 100% additional benefit not proven
Nivolumab (27) Opdivo® Bristol-Myers Squibb GmbH & Co. KGaA Oncological diseases Melanoma (stage IIB or IIC), adjuvant therapy, ≥ 12 years, monotherapy). 1,620–2,310 100% additional benefit not proven
Nivolumab (26) Opdivo® Bristol-Myers Squibb GmbH & Co. KGaA Oncological diseases Non-small cell lung cancer, PD-L1 expression ≥ 1 %, neoadjuvant therapy, combination with platinum-based chemotherapy 110–990 100% Hint for non-quantifiable additional benefit
Nivolumab (24) Opdivo® Bristol-Myers Squibb GmbH & Co. KGaA Oncological diseases Melanoma, adolescents ≥ 12 to 18 years, monotherapy or combination with ipilimumab). 2–4 100% additional benefit not proven
Nivolumab (25) Opdivo® Bristol-Myers Squibb GmbH & Co. KGaA Oncological diseases Melanoma, adjuvant therapy, adolescents ≥ 12 to 18 years, monotherapy 1–4 100% additional benefit not proven
Nivolumab (21) Opdivo® Bristol-Myers Squibb GmbH & Co. KGaA Oncological diseases Urothelial carcinoma (UC) PD-L1 expression ≥ 1 %, adjuvant therapy 350–460
1,030–1,290
65% Hint for non-quantifiable additional benefit repealed subpopulations
Nivolumab (22) Opdivo® Bristol-Myers Squibb GmbH & Co. KGaA Oncological diseases Squamous cell carcinoma of the oesophagus, PD-L1 expression ≥ 1, first-line, combination with platinum- and fluoropyrimidine-based chemotherapy 920–1,580 100% Indication of considerable additional benefit
Nivolumab (23) Opdivo® Bristol-Myers Squibb GmbH & Co. KGaA Oncological diseases Squamous cell carcinoma (SCC) of the oesophagus, PD-L1 expression ≥ 1, first-line, combination with ipilimumab 920–1,560 100% Hint for considerable additional benefit
Nivolumab (20) Opdivo® Bristol-Myers Squibb GmbH & Co. KGaA Oncological diseases Adenocarcinoma (AC) of the stomach, gastroesophageal junction or esophagus, CPS ≥ 5, HER2-negative, first-line, combination with fluoropyrimidine- and platinum-based combination chemotherapy 500–3,100 100% Hint for considerable additional benefit
Nivolumab (19) Opdivo® Bristol-Myers Squibb GmbH & Co. KGaA Oncological diseases Carcinoma of the esophagus and gastro-esophageal junction, pre-treated patients, adjuvant therapy 0
590–860
100% Indication of non-quantifiable additional benefit repealed
Nivolumab (18) Opdivo® Bristol-Myers Squibb GmbH & Co. KGaA Oncological diseases Colorectal carcinoma (CRC) with mismatch repair deficiency or high microsatellite instability, pre-treated patients, combination with ipilimumab 350–475 100% additional benefit not proven
Nivolumab (17) Opdivo® Bristol-Myers Squibb GmbH & Co. KGaA Oncological diseases Malignant pleural mesothelioma, first-line, combination with ipilimumab 160 50% Indication of considerable additional benefit
Nivolumab (16) Opdivo® Bristol-Myers Squibb GmbH & Co. KGaA Oncological diseases Renal cell carcinoma (RCC), first-line, combination with cabozantinib 2,790–4,180 100% additional benefit not proven
Nivolumab (15) Opdivo® Bristol-Myers Squibb GmbH & Co. KGaA Oncological diseases Melanoma, adjuvant therapy 3,450–4,350 100% Hint for considerable additional benefit
Nivolumab (14) Opdivo® Bristol-Myers Squibb GmbH & Co. KGaA Oncological diseases Squamous cell carcinoma of esophagus, pretreated patients 740–2,060 36% Hint for minor additional benefit
Nivolumab (13) Opdivo® Bristol-Myers Squibb Pharma EEIG Oncological diseases Non-small cell lung carcinoma (NSCLC), combination with ipilimumab and platinum-based chemotherapy, first-line 14,340–16,180 73% Indication of minor additional benefit
Nivolumab (12) Opdivo® Bristol-Myers Squibb GmbH & Co. KGaA Oncological diseases Renal cell carcinoma (RCC), first-line, combination with ipilimumab 2,110–2,850 100% Indication of considerable additional benefit
Nivolumab (11) Opdivo® Bristol-Myers Squibb GmbH & Co. KGaA Oncological diseases Melanoma, adjuvant therapy 0
2,980–3,780
100% Hint for non-quantifiable additional benefit repealed
Nivolumab (10) Opdivo® Bristol-Myers-Squibb GmbH & Co. KGaA Oncological diseases Melanoma, BRAF V600 wild-type, first-line, combination with ipilimumab 270–810 100% Indication of less benefit
Nivolumab (9) Opdivo® Bristol-Myers Squibb GmbH & Co. KGaA Oncological diseases Urothelial carcinoma (UC) 1,500–1,900 100% additional benefit not proven
Nivolumab (8) Opdivo® Bristol-Myers-Squibb GmbH & Co. KGaA Oncological diseases Melanoma, BRAF V600 wild-type, first-line, combination with ipilimumab 0
500–1,500
100% additional benefit not proven repealed
Nivolumab (7) Opdivo® Bristol-Myers Squibb GmbH & Co. KGaA Oncological diseases Squamous cell carcinoma head and neck 970–6,850 77% Hint for considerable additional benefit
Nivolumab (6) Opdivo® Bristol-Myers Squibb GmbH & Co. KGaA Oncological diseases Hodgkin lymphoma (HL) 40–90 100% additional benefit not proven
Nivolumab (5) Opdivo® Bristol-Myers-Squibb GmbH & Co. KGaA Oncological diseases Melanoma, combination with ipilimumab 2,230–3,690
2,500–4,500
100% additional benefit not proven repealed subpopulations
Nivolumab (3) Opdivo® Bristol-Myers Squibb GmbH & Co. KGaA Oncological diseases Renal cell carcinoma (RCC) 1,200–3,300 92% Indication of considerable additional benefit
Nivolumab (4) Opdivo® Bristol-Myers Squibb GmbH & Co. KGaA Oncological diseases Non-small cell lung carcinoma (NSCLC), non-squamous cell histology, after previous chemotherapy 11,830–21,830 40% Indication of considerable additional benefit
Nivolumab (2) Opdivo® Bristol-Myers Squibb GmbH & Co. KGaA Oncological diseases Non-small cell lung carcinoma (NSCLC), squamous cell histology, after previous chemotherapy 4,200–6,000 87% Indication of considerable additional benefit
Nivolumab (1) Opdivo® Bristol-Myers Squibb GmbH & Co. KGaA Oncological diseases Melanoma 2,500–4,500 15% Indication of considerable additional benefit


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