Nivolumab (18) – Opdivo®

Colorectal carcinoma (CRC) with mismatch repair deficiency or high microsatellite instability, pre-treated patients, combination with ipilimumab

Characteristics

Start date 01.08.2021 – Marketing authorisation: 24.06.2021
Resolution 20.01.2022
INN Nivolumab
Brand name Opdivo®
Pharm. company Bristol-Myers Squibb GmbH & Co. KGaA
G-BA Procedure ID D-717
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
DDD 17 mg P
Therapeutic area Oncological diseases Colorectal cancer (CRC) / Small intestine cancer
Reason for procedure New therapeutic indication

Therapeutic indication of the resolution

Opdivo is indicated in combination with ipilimumab for the treatment of metastatic colorectal cancer (CRC) with mismatch repair deficiency or high microsatellite instability in adults after prior fluoropyrimidine-based combination chemotherapy.

 

Subpopulation Indication Comparator
Adults with metastatic colorectal cancer (CRC) with mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H); after prior fluoropyrimidine-based combination therapy. 5-fluorouracil + folinic acid + irinotecan (FOLFIRI) ± bevacizumab or aflibercept or ramucirumab - 5-fluorouracil + folinic acid + irinotecan (FOLFIRI) ± cetuximab or panitumumab (only for patients with RAS wild type) - 5-fluorouracil + folinic acid + oxaliplatin (FOLFOX) ± bevacizumab - Capecitabine + oxaliplatin (CAPOX) ± bevacizumab - 5-fluorouracil + folinic acid ± bevacizumab - Capecitabine ± bevacizumab - Irinotecan as monotherapy - Panitumumab as monotherapy (only for patients with RAS wild type) - Cetuximab as monotherapy (only for patients with RAS wild type) - Trifluridine/tipiracil - Irinotecan + cetuximab (only for patients with RAS wild type) - Encorafenib + cetuximab (only for patients with BRAF V600E-mutation)

Studies and Results

No. of studies
(best subpopulation)
1 (CA209-6EP)
Study design
(best subpopulation)
Single-arm + ITC (PID/PSM)
Meta analysis
(best subpopulation)
no

  • Clinical trials
    • The CA209-142 study is an ongoing, open-label, uncontrolled clinical study involving 7 cohorts in a multicentre setting, as part of a prospective Phase II cohort study.

Adults with metastatic colorectal cancer with mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H); following prior fluoropyrimidine-based combination therapy

  • An additional benefit is not proven.
  • Overall, the data presented are not sufficient to demonstrate an additional benefit of nivolumab in combination with ipilimumab compared with the appropriate comparator therapy, and therefore the additional benefit of nivolumab in combination with ipilimumab is not proven for the treatment of metastatic colorectal cancer with mismatch repair deficiency or high microsatellite instability in adults following prior fluoropyrimidine-based combination chemotherapy.
  • mortality
    • For the endpoint of overall survival, a comparison of individual arms from different studies (Study CA209-6EP) was presented using various methods.
    • Particularly due to significant uncertainties arising from the identification, completeness and adjustment for confounders, the analyses presented in the dossier for study CA209-6EP are not suitable for assessing the additional benefit of nivolumab in combination with ipilimumab.
    • The analyses submitted for study CA209-6EP are therefore not suitable for assessing the additional benefit of nivolumab in combination with ipilimumab.
  • morbidity
    • For the endpoint categories of morbidity and health-related quality of life, the pharmaceutical manufacturer carried out before-and-after comparisons using data from CA209-142 (Cohort 2).
    • The results of the before-and-after comparisons from the CA209-142 study (Cohort 2) are not suitable for assessing the additional benefit of nivolumab in combination with ipilimumab in the endpoint categories of morbidity and health-related quality of life, as they do not allow for a comparison with the appropriate comparator therapy.
  • Health-related quality of life
    • Disease symptoms and health-related quality of life are assessed in the CA209-142 study using the cancer-specific EORTC QLQ-C30 questionnaire.
    • Health status is assessed using the visual analogue scale (VAS) of the EQ-5D.
    • The results of the before-and-after comparisons in study CA209-142 (Cohort 2) are not suitable for assessing the additional benefit of nivolumab in combination with ipilimumab in the endpoint categories of morbidity and health-related quality of life, as they do not allow for a comparison with the appropriate comparator therapy.
  • Side effects
    • Overall, the descriptive comparison is not suitable for assessing the additional benefit of nivolumab in combination with ipilimumab.
  • Conclusion
    • Overall, the data presented are not suitable for demonstrating any additional benefit of nivolumab in combination with ipilimumab compared with the appropriate comparator therapy; therefore, no additional benefit of nivolumab in combination with ipilimumab is proven.

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


<< List of all resolutions