Nivolumab (16) – Opdivo®

Renal cell carcinoma (RCC), first-line, combination with cabozantinib

Characteristics

Start date 01.05.2021 – Marketing authorisation: 13.04.2021
Resolution 21.10.2021
INN Nivolumab
Brand name Opdivo®
Pharm. company Bristol-Myers Squibb GmbH & Co. KGaA
G-BA Procedure ID D-684
ATC code L01FF01 PD-1/PDL-1 inhibitors (L01FF)
ICD-10 codes (AIS) C64Malignant neoplasm of kidney, except renal pelvis
Alpha-ID codes (AIS) I19876Renal cell carcinoma
DDD 17 mg P
Therapeutic area Oncological diseases Renal cell carcinoma (RCC)
Reason for procedure New therapeutic indication
Specialty Bundling Combination therapy

Therapeutic indication of the resolution

OPDIVO in combination with cabozantinib is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma

Subpopulation Indication Comparator
a) Adult patients with non-pretreated advanced renal cell carcinoma (RCC) with favorable risk profile (IMDC score 0) Pembrolizumab in combination with Axitinib
b) Adult patients with non-pretreated advanced renal cell carcinoma (RCC) With intermediate (IMDC score 1-2) or unfavorable risk profile (IMDC score ≥ 3) - Avelumab in combination with axitinib (only for patients with an unfavourable risk profile) or – Nivolumab in combination with ipilimumab or – Pembrolizumab in combination with axitinib

Studies and Results

No. of studies
(best subpopulation)
1 (CheckMate 9 ER)
Study design
(best subpopulation)
H2H vs. non-ACT + ITC (Bucher)
Meta analysis
(best subpopulation)
yes
Reason for dividing into subpopulations (G-BA) Disease stage

a) Adult patients with previously untreated, advanced renal cell carcinoma with a favourable risk profile (IMDC score 0)

  • Additional benefit is not proven for nivolumab in combination with cabozantinib compared with the appropriate comparator therapy.
  • The adjusted indirect comparison submitted by the pharmaceutical manufacturer of nivolumab in combination with cabozantinib (CheckMate 9ER) versus pembrolizumab in combination with axitinib (KEYNOTE-426) includes patients with any risk profile.
  • The pharmaceutical manufacturer has not provided a separate analysis of patient population a) from the adjusted indirect comparison of nivolumab in combination with cabozantinib versus pembrolizumab in combination with axitinib.
  • Consequently, there are no suitable data available to assess the additional benefit of nivolumab in combination with cabozantinib for patient population (a).

b) Adult patients with untreated, advanced renal cell carcinoma with an intermediate (IMDC score 1–2) or unfavourable risk profile (IMDC score ≥ 3)

  • An additional benefit of nivolumab in combination with cabozantinib compared with the appropriate comparator therapy is not proven.
  • In the absence of direct comparative studies of nivolumab in combination with cabozantinib versus the appropriate comparator therapy, the pharmaceutical manufacturer presents a total of three adjusted indirect comparisons using the procedure described by Bucher et al.
  • In doing so, it considers the following populations: patients with any risk profile, patients with an intermediate or unfavourable risk profile, and patients with an unfavourable risk profile.
  • The pharmaceutical manufacturer does not allocate the results to the separate patient populations a) and b).
  • Consequently, there is no separate analysis for patient population b) taking all three adjusted indirect comparisons into account.
  • Overall, therefore, there are no suitable data available for assessing the additional benefit of nivolumab in combination with cabozantinib for patient population b).

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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