Pembrolizumab (20) – Keytruda®

Advanced renal cell carcinoma (RCC), first-line, combination with lenvatinib

Characteristics

Start date 15.12.2021 – Marketing authorisation: 15.11.2021
Resolution 07.07.2022
INN Pembrolizumab
Brand name Keytruda®
Pharm. company MSD Sharp & Dohme GmbH
G-BA Procedure ID D-763
ATC code L01FF02 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 9.5 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

Keytruda, in combination with lenvatinib, is indicated for the first-line treatment of advanced renal cell carcinoma in adults
Subpopulation Indication Comparator
a) Adults with non-pretreated, advanced renal cell carcinoma (RCC) with a favourable risk profile (IMDC score 0) Pembrolizumab in combination with Axitinib
b) Adults with non-pretreated, advanced renal cell carcinoma with intermediate (IMDC score 1-2) or unfavourable 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 (CLEAR)
Study design
(best subpopulation) 		H2H vs. non-ACT + ITC (Bucher)
Meta analysis
(best subpopulation) 		no
Reason for dividing into subpopulations (G-BA) Disease stage

  • Clinical trials
    • In the KEYNOTE 426 trial, pembrolizumab in combination with axitinib was compared with sunitinib. The trial included adults with advanced or metastatic clear cell renal cell carcinoma.

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

  • An additional benefit is not proven.
  • A key prerequisite for an adjusted indirect comparison is the assumption of sufficient similarity between the studies. This includes similarity of the patient population; however, this could not be adequately assessed in the present evaluation, as relevant data on the relevant patient populations from the CLEAR and KEYNOTE 426 trials are not available.
  • Overall, based on the available data, it cannot be established with sufficient certainty that the patient populations are sufficiently similar for the indirect comparison.
  • Consequently, no suitable data are available for assessing the additional benefit of pembrolizumab in combination with lenvatinib in patient group a).

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

  • The additional benefit is not proven.
  • A key prerequisite for an adjusted indirect comparison is the assumption of sufficient similarity between the studies. This includes similarity of the patient population; however, this could not be adequately assessed in the present evaluation, as relevant data on the relevant patient populations from the CLEAR and KEYNOTE 426 trials are not available.
  • Overall, based on the available data, it cannot be established with sufficient certainty that the patient populations are sufficiently similar for the indirect comparison.
  • Consequently, there are no suitable data available for assessing the additional benefit of pembrolizumab in combination with lenvatinib in patient group b).

Courtesy translation only, please refer to the German original.

Associated procedures

Pembrolizumab (41) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Resectable locally advanced squamous cell carcinoma of the head and neck, PD-L1 expression ≥ 1 per cent, neoadjuvant and adjuvant therapy, in combination with radiotherapy with or without concomitant cisplatin therapy 2,550–4,240 86% Hint for minor additional benefit
Pembrolizumab (40) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Malignant pleural mesothelioma, non-epithelioid, first-line treatment, in combination with pemetrexed and platinum-based chemotherapy 55–105 100% additional benefit not proven
Pembrolizumab (38) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Cervical carcinoma (stage III to IVA), first-line, combination with radiochemotherapy 750 100% Indication of non-quantifiable additional benefit
Pembrolizumab (39) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Endometrial carcinoma, first-line, combination with carboplatin and paclitaxel 1,370–3,330 100% additional benefit not proven
Pembrolizumab (36) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Urothelial carcinoma, non-resectable or metastatic, first-line, combination with enfortumab vedotin 1,050–2,601 39% Indication of considerable additional benefit
Pembrolizumab (37) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Breast cancer, triple-negative, high risk of recurrence, neoadjuvant and adjuvant therapy, monotherapy or combination with chemotherapy 2,440–2,610 50% Indication of minor additional benefit
Pembrolizumab (35) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Non-small cell lung cancer, high risk of recurrence, neoadjuvant and adjuvant therapy, monotherapy or combination with platinum-based chemotherapy 5,090–6,780 100% additional benefit not proven
Pembrolizumab (34) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Non-small cell lung cancer, adjuvant therapy with high risk of recurrence after resection, after prior chemotherapy 2,690–3,200 100% additional benefit not proven
Pembrolizumab (32) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Adenocarcinoma of the stomach or gastroesophageal junction, PD-L1 expression ≥ 1, HER2, first-line, combination with fluoropyrimidine- and platinum-based chemotherapy 285–2,613 100% additional benefit not proven
Pembrolizumab (33) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Biliary tumours, first-line, combination with gemcitabine and cisplatin 1,480–2,180 100% Indication of minor additional benefit
Pembrolizumab (31) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Adenocarcinoma of the stomach or gastroesophageal junction, PD-L1 expression ≥ 1, HER2+, first-line, combination with trastuzumab, fluoropyrimidine- and platinum-based chemotherapy 70–710 100% additional benefit not proven
Pembrolizumab (28) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Cervical carcinoma, PD-L1 expression ≥ 1 (CPS), combination with or without bevacizumab 1,315–1,525 40% Indication of considerable additional benefit
Pembrolizumab (30) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Melanoma, ≥ 12 to < 18 years 1–4 100% additional benefit not proven
Pembrolizumab (22) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Renal cell carcinoma (RCC), adjuvant, monotherapy, pre-treated patients 1,518–1,973 100% Hint for minor additional benefit
Pembrolizumab (23) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Colorectal cancer (CRC)) with MSI-H or with dMMR, after fluoropyrimidine-based combination therapy. 350–1,470 100% additional benefit not proven
Pembrolizumab (24) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Endometrial carcinoma with MSI-H or with dMMR, pre-treated 230–3,360 100% additional benefit not proven
Pembrolizumab (25) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Gastric carcinoma with MSI-H or dMMR, pre-treated 80–110 74% Hint for non-quantifiable additional benefit
Pembrolizumab (26) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Small bowel carcinoma with MSI-H or dMMR, pre-treated 40–380 100% additional benefit not proven
Pembrolizumab (27) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Biliary carcinoma with MSI-H or dMMR, pre-treated 20–150 100% additional benefit not proven
Pembrolizumab (29) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Melanoma, adjuvant therapy, ≥ 12 years, monotherapy 1,621–2,314 100% Indication of non-quantifiable additional benefit
Pembrolizumab (21) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Breast carcinoma (BC), triple-negative (TNBC), high risk of recurrence, neoadjuvant and adjuvant therapy, monotherapy or combination with chemotherapy 0
2,440–2,520 		50% Hint for minor additional benefit repealed
Pembrolizumab (19) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Endometrial carcinoma (EC) , after platinum-based therapy, combination with lenvatinib 1,130–5,070 100% Indication of considerable additional benefit
Pembrolizumab (20) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Advanced renal cell carcinoma (RCC), first-line, combination with lenvatinib 2,790–4,189 100% additional benefit not proven
Pembrolizumab (17) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Carcinoma of the esophagus or gastroesophageal junction, PD-L1 expression ≥ 10 (CPS), first-line, combination with platinum- and fluoropyrimidine-based chemotherapy. 535–805 34% Indication of considerable additional benefit
Pembrolizumab (18) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Breast cancer (BC), triple-negative, PD-L1 expression ≥ 10 (CPS), combination with chemotherapy 260–270 50% Hint for considerable additional benefit
Pembrolizumab (14) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Hodgkin lymphoma (HL), pre-treated patients, ≥ 3 years 120–240 46% Hint for considerable additional benefit
Pembrolizumab (16) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Urothelial carcinoma (UC), CPS ≥ 10, first-line 225–380 100% additional benefit not proven
Pembrolizumab (15) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Colorectal carcinoma (CRC) with MSI-H or dMMR, first-line 370–955 87% Hint for minor additional benefit
Pembrolizumab (12) Keytruda® MSD SHARP & DOHME GMBH Oncological diseases Renal cell carcinoma (RCC), first-line, combination with axitinib 3,500 23% Indication of considerable additional benefit
Pembrolizumab (13) Keytruda® MSD SHARP & DOHME GMBH Oncological diseases Squamous cell carcinoma head and neck, PD-L1 expression ≥ 1%, first-line, combination with platinum and 5-fluorouracil (5-FU) chemotherapy 4,950–5,370 100% Indication of minor additional benefit
Pembrolizumab (11) Keytruda® MSD SHARP & DOHME GMBH Oncological diseases Squamous cell carcinoma head and neck, PD-L1 expression ≥ 1%, first-line, monotherapy 4,955–5,370 100% Hint for considerable additional benefit
Pembrolizumab (10) Keytruda® MSD SHARP & DOHME GMBH Oncological diseases Non-small cell lung carcinoma (NSCLC), squamous cell histology, first-line, combination with carboplatin and (nab-) paclitaxel 5,340–5,570 71% Hint for considerable additional benefit
Pembrolizumab (9) Keytruda® MSD SHARP & DOHME GMBH Oncological diseases Non-small cell lung carcinoma (NSCLC), non-squamous cell histology, first-line, combination with pemetrexed and platinum chemotherapy 8,020–9,120 100% Hint for non-quantifiable additional benefit
Pembrolizumab (8) Keytruda® MSD SHARP & DOHME GMBH Oncological diseases Melanoma, adjuvant therapy 2,670–3,400 100% Indication of non-quantifiable additional benefit
Pembrolizumab (7) Keytruda® MSD SHARP & DOHME GMBH Oncological diseases Urothelial carcinoma (UC), CPS ≥ 10, first-line 0
240–420 		100% additional benefit not proven repealed
Pembrolizumab (6) Keytruda® MSD SHARP & DOHME GMBH Oncological diseases Squamous cell carcinoma head and neck 470–3,290 100% additional benefit not proven
Pembrolizumab (5) Keytruda® MSD SHARP & DOHME GMBH Oncological diseases Urothelial carcinoma (UC) 0
2,300–3,300 		61% Indication of considerable additional benefit repealed
Pembrolizumab (4) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Hodgkin lymphoma (HL) 60–180 100% additional benefit not proven
Pembrolizumab (3) Keytruda® MSD SHARP & DOHME GMBH Oncological diseases Non-small cell lung carcinoma (NSCLC), first-line 4,000 100% Indication of considerable additional benefit
Pembrolizumab (2) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Non-small cell lung carcinoma (NSCLC), after prior chemotherapy 12,500–24,300 40% Indication of considerable additional benefit
Pembrolizumab (1) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Melanoma 2,500–4,500 71% Indication of considerable additional benefit


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